- Source: Mood, stress and longevity: convergence on ANK3.
- Abstract: Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. We sought to understand the underlying biology. First, we analyzed the transcriptome from worms treated with the antidepressant mianserin, previously identified in a large-scale unbiased drug screen as promoting increased lifespan in worms. We identified the most robust treatment-related changes in gene expression, and identified the corresponding human orthologs. Our analysis uncovered a series of genes and biological pathways that may be at the interface between antidepressant effects and longevity, notably pathways involved in drug metabolism/degradation (nicotine and melatonin). Second, we examined which of these genes overlap with genes which may be involved in depressive symptoms in an aging non-psychiatric human population (n=3577), discovered using a genome-wide association study (GWAS) approach in a design with extremes of distribution of phenotype. Third, we used a convergent functional genomics (CFG) approach to prioritize these genes for relevance to mood disorders and stress. The top gene identified was ANK3. To validate our findings, we conducted genetic and gene-expression studies, in C. elegans and in humans. We studied C. elegans inactivating mutants for ANK3/unc-44, and show that they survive longer than wild-type, particularly in older worms, independently of mianserin treatment. We also show that some ANK3/unc-44 expression is necessary for the effects of mianserin on prolonging lifespan and survival in the face of oxidative stress, particularly in younger worms. Wild-type ANK3/unc-44 increases in expression with age in C. elegans, and is maintained at lower youthful levels by mianserin treatment. These lower levels may be optimal in terms of longevity, offering a favorable balance between sufficient oxidative stress resistance in younger worms and survival effects in older worms. Thus, ANK3/unc-44 may represent an example of antagonistic pleiotropy, in which low-expression level in young animals are beneficial, but the age-associated increase becomes detrimental. Inactivating mutations in ANK3/unc-44 reverse this effect and cause detrimental effects in young animals (sensitivity to oxidative stress) and beneficial effect in old animals (increased survival). In humans, we studied if the most significant single nucleotide polymorphism (SNP) for depressive symptoms in ANK3 from our GWAS has a relationship to lifespan, and show a trend towards longer lifespan in individuals with the risk allele for depressive symptoms in men (odds ratio (OR) 1.41, P=0.031) but not in women (OR 1.08, P=0.33). We also examined whether ANK3, by itself or in a panel with other top CFG-prioritized genes, acts as a blood gene-expression biomarker for biological age, in two independent cohorts, one of live psychiatric patients (n=737), and one of suicide completers from the coroner's office (n=45). We show significantly lower levels of ANK3 expression in chronologically younger individuals than in middle age individuals, with a diminution of that effect in suicide completers, who presumably have been exposed to more severe and acute negative mood and stress. Of note, ANK3 was previously reported to be overexpressed in fibroblasts from patients with Hutchinson-Gilford progeria syndrome, a form of accelerated aging. Taken together, these studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and longevity/aging, that may be biomarkers as well as targets for preventive or therapeutic interventions. Drug repurposing bioinformatics analyses identified the relatively innocuous omega-3 fatty acid DHA (docosahexaenoic acid), piracetam, quercetin, vitamin D and resveratrol as potential longevity promoting compounds, along with a series of existing drugs, such as estrogen-like compounds, antidiabetics and sirolimus/rapamycin. Intriguingly, some of our top candidate genes for mood and stress-modulated longevity were changed in expression in opposite direction in previous studies in the Alzheimer disease. Additionally, a whole series of others were changed in expression in opposite direction in our previous studies on suicide, suggesting the possibility of a "life switch" actively controlled by mood and stress.
- Source: Phlebotonics for venous insufficiency.
- Abstract: BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.
- Source: Moisturising and Antiinflammatory Properties of Cosmetic Formulations Containing Centella asiatica Extract.
- Abstract: Centella asiatica extract is a rich source of natural bioactive substances, triterpenoid saponins, flavonoids, phenolic acids, triterpenic steroids, amino acids and sugars. Thus, many scavenging free radicals, exhibit antiinflammatory activity and affect on the stratum corneum hydration and epidermal barrier function. The aim of the present study was to evaluate the in vivo moisturizing and antiinflammatory properties of cosmetic formulations (oil-in-water emulsion cream and hydrogel) containing different concentrations of Centella asiatica extract. The study was conducted over four weeks on a group of 25 volunteers after twice a day application of cosmetic formulations with Centella asiatica extract (2.5 and 5%, w/w) on their forearms. The measurement of basic skin parameters (stratum corneum hydration and epidermal barrier function) was performed once a week. The in vivo antiinflammatory activity based on the methyl nicotinate model of microinflammation in human skin was evaluated after four weeks application of tested formulations. In vivo tests formulations containing 5% of Centella asiatica extract showed the best efficacy in improving skin moisture by increase of skin surface hydration state and decrease in transepidermal water loss as well as exhibited antiinflammatory properties based on the methyl nicotinate model of microinflammation in human skin. Comparative tests conducted by corneometer, tewameter and chromameter showed that cosmetic formulations containing Centella asiatica extract have the moisturizing and antiinflammatory properties.
- Source: Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization.
- Abstract: SCOPE: Obesity is closely related to the imbalance of white adipose tissue storing excess calories, and brown adipose tissue dissipating energy to produce heat in mammals. Recent studies revealed that acquisition of brown characteristics by white adipocytes, termed "browning," may positively contribute to cellular bioenergetics and metabolism homeostasis. The goal was to investigate the putative effects of natural antioxidant sulforaphane (1-isothiocyanate-4-methyl-sulfonyl butane; SFN) on browning of white adipocytes. METHODS AND RESULTS: 3T3-L1 mature white adipocytes were treated with SFN for 48 h, and then the mitochondrial content, function, and energy utilization were assessed. SFN was found to induce 3T3-L1 adipocytes browning based on the increased mitochondrial content and activity of respiratory chain enzymes, whereas the mechanism involved the upregulation of nuclear factor E2-related factor 2/ sirtuin1/ peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) signaling. SFN enhanced uncoupling protein 1 expression (UCP1), a marker for brown adipocyte, leading to the decrease in cellular ATP. SFN also enhanced glucose uptake and oxidative utilization, lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. CONCLUSION: SFN-induced browning of white adipocytes enhanced the utilization of cellular fuel, and SFN is a promising strategy to combat obesity and obesity-related metabolic disorder. This article is protected by copyright. All rights reserved.
- Source: Effects of glucose and insulin on secretion of amyloid-β by human adipose tissue cells.
- Abstract: OBJECTIVE: Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Overlapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid-β (Aβ) precursor protein and associated β- and γ-secretases are expressed in adipose tissue. Aβ precursor protein is up-regulated with obesity and correlated to insulin resistance. Aβ may be secreted by adipose tissue, its production may be regulated through metabolic pathways, and Aβ may exert effects on adipose tissue insulin receptor singling. METHODS: Human stromal-vascular cells and differentiated adipocytes were cultured with different combinations of glucose and insulin and then assayed for Aβ in conditioned media. Aβ was measured in vivo using adipose tissue micro dialysis. RESULTS: Aβ secretion was increased by glucose and insulin in vitro. Adipose tissue microdialysates contained Aβ. Adipocytes treated with Aβ had decreased expression of insulin receptor substrate-2 and reduced Akt-1 phosphorylation. CONCLUSIONS: Aβ was made by adipose tissue cells in vitro at concentrations similar to in vivo measurements. Regulation of Aβ production by glucose and insulin and effects of Aβ on the insulin receptor pathway suggest similar cellular mechanisms may exist between neuronal dysfunction in Alzheimer disease and adipose dysfunction in type 2 diabetes.
- After studying thousands of genes on thousands of people, researchers in Holland have found that the carriers of a specific subtype of the gene MC1R look two years younger than their biological age
- MC1R (melanocortin 1 receptor) controls the protein that converts inactive yellow/red melanin to brown/black melanin and leads to tanning, but the authors of the study have stated that the results are independent of skin colour or indeed "age, sex and sun damage (wrinkling, pigmented spots) and persisted through different sun-exposure levels"
- Two years is not an enormous difference - many people look a decade or more younger than their biological age, especially black or oriental people, and definitely there are dozens of other factors at play. Nevertheless, this is still a beginning in identifying ways to boost youthfulness and beauty based on information gleaned from genetics.
- Source: The MC1R Gene and Youthful Looks
- Abstract: Looking young for one's age has been a desire since time immemorial. This desire is attributable to the belief that appearance reflects health and fecundity. Indeed, perceived age predicts survival  and associates with molecular markers of aging such as telomere length . Understanding the underlying molecular biology of perceived age is vital for identifying new aging therapies among other purposes, but studies are lacking thus far. As a first attempt, we performed genome-wide association studies (GWASs) of perceived facial age and wrinkling estimated from digital facial images by analyzing over eight million SNPs in 2,693 elderly Dutch Europeans from the Rotterdam Study. The strongest genetic associations with perceived facial age were found for multiple SNPs in the MC1R gene (p < 1 × 10(-7)). This effect was enhanced for a compound heterozygosity marker constructed from four pre-selected functional MC1R SNPs (p = 2.69 × 10(-12)), which was replicated in 599 Dutch Europeans from the Leiden Longevity Study (p = 0.042) and in 1,173 Europeans of the TwinsUK Study (p = 3 × 10(-3)). Individuals carrying the homozygote MC1R risk haplotype looked on average up to 2 years older than non-carriers. This association was independent of age, sex, skin color, and sun damage (wrinkling, pigmented spots) and persisted through different sun-exposure levels. Hence, a role for MC1R in youthful looks independent of its known melanin synthesis function is suggested. Our study uncovers the first genetic evidence explaining why some people look older for their age and provides new leads for further investigating the biological basis of how old or young people look.
- Source: A short bout of HFD promotes long-lasting hepatic lipid accumulation.
- Abstract: A short bout of high fat diet (HFD) impairs glucose tolerance and induces hepatic steatosis in mice. Here, we aimed to elaborate on long-lasting effects of short-term high fat feeding. As expected, one week of HFD significantly impaired glucose tolerance. Intriguingly, recovery feeding with a standard rodent diet for 8 weeks did not fully normalize glucose tolerance. In addition, mice exposed to a short bout of HFD revealed significantly increased liver fat accumulation paralleled by elevated portal free fatty acid levels after 8 weeks of recovery feeding compared to exclusively chow-fed littermates. In conclusion, a short bout of HFD has long-lasting effects on hepatic lipid accumulation and glucose tolerance.
- Source: Wasabi leaf extracts attenuate adipocyte hypertrophy through PPARγ and AMPK.
- Abstract: Hypertrophy of adipocytes in obese adipose tissues causes metabolic abnormality by adipocytokine dysregulation, which promotes type 2 diabetes mellitus, hypertension, and dyslipidemia. We investigated the effects of wasabi (Wasabia japonica Matsum) leaf extracts on metabolic abnormalities in SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a model of metabolic syndrome. Male SHRSP/ZF rats aged 7 weeks were divided into two groups: control and wasabi leaf extract (WLE) groups, which received water or oral treatment with 4 g/kg/day WLE for 6 weeks. WLE improved the body weight gain and high blood pressure in SHRSP/ZF rats, and the plasma triglyceride levels were significantly lower in the WLE group. Adipocyte hypertrophy was markedly prevented in adipose tissue. The expression of PPARγ and subsequent downstream genes was suppressed in the WLE group adipose tissues. Our data suggest that WLE inhibits adipose hypertrophy by suppressing PPARγ expression in adipose tissue and stimulating the AMPK activity by increased adiponectin.
- The so-called activated thyroid hormone triiodothyronine (T3), in contrast to the relative inactive T4/thyroxine, has been found to boost fat accumulation in fat cells by boosting fatty acid synthase/FAS and inhibiting hormone sensitive lipase/HSL.
- Thyroid hormone is well know to help with weight loss, but as this study shows it actually has an anabolic role on fat tissue, which means that triiodothyronine excerpts it's slimming effect by boosting metabolism in muscles and organs, then by acting on fat cells directly.
- Source: Triiodothyronine enhances accumulation of intracellular lipids in adipocytes through thyroid hormone receptor α via direct and indirect mechanisms.
- Abstract: Triiodothyronine (T3) enhanced the expression of adipogenic and lipogenic genes with elevation of the intracellular lipids through thyroid hormone receptor (TR) α in mouse 3T3-L1 cells. However, the transcription of the SREBP-1c and HSL genes was decreased by T3. Such T3-mediated alterations were negated by TRα siRNA. Chromatin immunoprecipitation assay showed that the binding of TRα to the TR-responsive element (TRE) of the FAS promoter was elevated by T3. In contrast, the ability of TRα to bind to the TRE of the SREBP-1c promoter was decreased by T3. In addition, the binding of SREBP-1c to the SRE of the HSL promoter was lowered by T3. These results indicate that T3 increased the accumulation of intracellular lipids by enhancing the expression of the FAS gene through direct binding of TRα to the FAS promoter and simultaneously lowered the amount of lipolysis via reduced binding of T3-decreased SREBP-1c to the HSL promoter.
- The flavonoid chrysin has been found to boost fat metabolism in adipocytes (fat cells) and also to boost the conversion of fat accumulating white fat cells to fat burning brown fat cells
- Chrysin is already used in food supplements for it's multiple benefits on health and the authors of the study state that "it may be explored as a potentially promising food additive for prevention of obesity"
- Due to it's action on fat release, chrysin could also be useful as an active ingredient in cellulite creams
- Source: Chrysin induces brown fat-like phenotype and enhances lipid metabolism in 3T3-L1 adipocytes.
- Abstract: OBJECTIVES: Many studies have to do with promising therapeutic phytochemicals such as flavonoids to treat obesity and related complications, and a number of dietary compounds have been proposed as tools for increasing energy expenditure and decreasing fat accumulation in mammals. Here, we show that the flavonoid chrysin induces browning of 3T3-L1 adipocytes via enhanced expression of brown fat-specific genes and proteins as well as enhances lipid metabolism. METHODS: Chrysin-induced fat browning was investigated by determining expression levels of brown fat-specific genes and proteins by real-time polymerase chain reaction and immunoblot analysis, respectively. RESULTS: Chrysin enhanced expression of brown fat-specific markers and increased protein levels of peroxisome proliferator-activated receptor (PPAR)α, PPARγ, PPARδ, phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase, hormone sensitive lipase, perilipin, carnitine palmitoyltransferase 1, acyl-coenzyme A oxidase 1, peroxisome proliferator-activated receptor-1 alpha (PGC-1α), and uncoupling protein 1 (UCP-1), suggesting its possible role in augmentation of lipolysis, fat oxidation, and thermogenesis as well as reduction of lipogenesis. Increased expression of UCP-1 and other brown fat-specific markers was possibly mediated by chrysin-induced activation of AMPK based on the fact that inhibition of AMPK by dorsomorphin abolished expression of PR domain-containing 16, UCP-1, and PGC-1α while the activator 5-aminoimidazole-4-carboxamide ribonucleotide elevated expression of these brown marker proteins. CONCLUSION: Our findings suggest that chrysin plays a dual modulatory role in the form of inducing the brown-like phenotype as well as enhancing lipid metabolism and thus may be explored as a potentially promising food additive for prevention of obesity.
- In a recent study it was found that chronic, low level treatment with a carbon monoxide-releasing molecule has been shown to prevent the development of obesity in response to a high fat diet.
- Carbon monoxide is a well known poison produced from incomplete oxidation/burning (including smoking), and as is widely known high levels will lead to asphyxia and death.
- Furthermore, scientists found that inhaling carbon monoxide only had a short term effect on weight loss in mice.
- However, when used over 30 weeks, low levels carbon monoxide released by a novel carbon monoxide-releasing molecule actually reduced obesity, and also obesity-related inflammation, insulin resistance and liver damage.
- This could be one of the mechanisms by which smoking helps prevent weight gain (together with the inhibitory effect of nicotine on fact cells and on appetite).
- However, I would urge anyone to take up smoking just to benefit from this effect, as smoking has a negative effect on circulation and also encourages the growth of fibrosis, collagen breakdown, leading to cellulite development, despite it's inhibitory effect on fat growth. Not to mention the risk of cancer and cardiovascular disease, due to the molecules contained in tar...
- For the moment we have to wait, probably for several years, if a safe and effective anti-obesity treatment can be offered based on this breakthrough, or even an anti-cellulite cream, based on this specific or a similar molecule.
- Source: Chronic treatment with a carbon monoxide releasing molecule reverses dietary induced obesity in mice.
- Abstract: Chronic, low level treatment with a carbon monoxide releasing molecule (CO-RM), CORM-A1, has been shown to prevent the development of obesity in response to a high fat diet. The objective of this study was to test the hypothesis that chronic, low level treatment with this CO-RM can reverse established obesity via a mechanism independent of food intake. Dietary induced obese mice were treated with CORM-A1, the inactive compound iCORM-A1, or saline every 48 hours for 30 weeks while maintained on a high fat (60%) diet. Chronic treatment with CORM-A1 resulted in a 33% decrease from initial body weight over the 30 week treatment period while treatment with iCORM and saline were associated with 18 and 25% gain in initial body weight over the same time frame. Chronic treatment with CORM-A1 did not affect food intake or activity but resulted in a significant increase in metabolism. CORM-A1 treatment also resulted in lower fasting blood glucose, improvement in insulin sensitivity and decreased heptatic steatosis. Chronic treatment with CO releasing molecules can reverse dietary induced obesity and normalize insulin resistance independent of changes in food intake or activity. These findings are likely though a mechanism which increases metabolism.
- According to recent communication and action from the FDA, if a cosmetic active ingredient actually works it's a drug and should be banned. And if it doesn't work, well, it doesn't work and misleads consumers, so it should be banned too.
- Long story short, nothing that actually does something should be own the market and no-one except pharmaceuticals and doctors can make any claims, ESPECIALLY if the make scientifically established claims based on research and clinical data. The more scientifically proven the claim, the more the FDA has a case that the product is a "drug".
- According to this "Holly Inquisition" doctrine, there can be no cosmetic products that actually do something on the skin, such as creams with collagen boosting actives or skin lightening ones, as these are supposedly "medical interventions" and turn these products into "unlicensed drugs" and companies that educate their customers about the benefits of such natural, healthful actives face fines and prosecution.
- So if you use a $20 vitamin C cream on your skin (vitamin C is very, very well researched for it's skin lightening and collagen stimulating action, and of course super-safe), according to the FDA you are using a dangerous unlicensed "drug", which has first to be approved as a medicine (after decade-long trials). Only then it can be prescribed by a doctor and bought as a medicine from the pharmacy, for possibly something like $200.
- Of course, no-one can patent vitamin C and no pharma will bother manufacturing it for this purpose, so thanks to the FDA there can exist no skin product that makes claims about the skin lightening / collagen boosting properties of vitamin C (or any other natural active that actually works) without falling fall foul of the FDA's interventionist, undemocratic, dictatorial rule. All that are allowed for claims are makeup, exfoliants and moisturisers. And who knows, maybe at some point the FDA will decide that moisturisation or exfoliation "intends to affect the structure or function of the human body", and those will be banned too...
- The situation with the FDA in the US is ridiculous and bordering on the grotesque, and for the time being no US lawmaker seems to be willing to end the tyranny of this unelected organisation upon anything natural, healthful, wholesome or non-pharmaceutical.
- This is not the medieval times, it is 2016 and science is institutionally banned from a major government agency in the most advanced economy in the world, in the name of protecting the public from itself. Sad and pathetic...
- Source: FDA Warns About Stimulating Collagen, Lightening and Other Claims, http://www.cosmeticsandtoiletries.com/regulatory/claims/FDA-Warns-About-Stimulating-Collagen-Lightening-and-Other-Claims-380125521.html
- The flavonoid rutin, a chemical relative to quercetin, has been found to inhibit adipose tissue growth and expansion, by blocking multiple adipose tissue growth factors (PPAR-gamma, FABP, FAS, lipin1 and C/EBP), showing another mechanism by which rutin can fight cellulite
- The other mechanism is of course the action of rutin against water retention, by protecting capillaries, larger blood vessels and microcirculation, in general.
- For these reasons, rutin is an ideal natural active in cellulite creams
- Source: Lipin1-Mediated Repression of Adipogenesis by Rutin.
- Abstract: Rutin, also called rutoside or quercetin-3-O-rutinoside and sophorin, is a glycoside between the flavonol quercetin and the disaccharide rutinose. Although many effects of rutin have been reported in vitro and in vivo, the anti-adipogenic effects of rutin have not been fully reported. The aim of this study was to confirm how rutin regulates adipocyte related factors. In this study, rutin decreased the expressions of adipogenesis-related genes, including peroxisome proliferators, activated receptor [Formula: see text] (PPAR[Formula: see text], CCAAT/enhancer-binding protein [Formula: see text] (C/EBP[Formula: see text], fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase in 3T3-L1 cells. Rutin also repressed the expression of lipin1, which is an upstream regulator that controls PPAR[Formula: see text] and C/EBP[Formula: see text]. In addition, when 3T3-L1 was transfected with lipin1 siRNA to block lipin1 function, rutin did not affect the expressions of PPAR[Formula: see text] and C/EBP[Formula: see text]. These results suggest that rutin has an anti-adipogenic effect that acts through the suppression of lipin1, as well as PPAR and C/EBP.
- New research shows that, contrary to what was believed in the past, the stress hormone cortisol does not lead to fat accumulation in adipose tissue
- However, the study shows that cortisol protects fat cells from adipocyte inflammation, a major cause of metabolic disease
- Source: Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth.
- Abstract: The glucocorticoids bind and activate both the glucocorticoid receptor (GR) as well as the mineralocorticoid receptor (MR) in adipocytes. Despite several studies to determine the function of these two receptors in mediating glucocorticoids effects, their relative contribution in adipose tissue expansion and obesity is unclear. To investigate the effect of GR in adipose tissue function, we generated an adipocyte specific GR knockout mouse model (GRad-ko). These mice were submitted either to a standard diet or a high fat high sucrose diet. We found that adipocyte specific deletion of GR did not affect body weight gain or adipose tissue formation and distribution. However, the lack of GR in adipocyte promotes a diet-induced inflammation determined by higher pro-inflammatory genes expression and macrophage infiltration in the fat pads. Surprisingly, the adipose tissue inflammation in GRad-ko mice was not correlated with insulin resistance or dyslipidemia, but with disturbed glucose tolerance. Our data demonstrate that adipocyte specific ablation of GR in vivo may affect the adipose tissue function but not its expansion during a high calorie diet.
- Source: Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota.
- Abstract: The gut microbiota is found to be strongly associated with atherosclerosis (AS). Resveratrol (RSV) is a natural phytoalexin with anti-AS effects; however, its mechanisms of action remain unclear. Therefore, we sought to determine whether the anti-AS effects of RSV were related to changes in the gut microbiota. We found that RSV attenuated trimethylamine-N-oxide (TMAO)-induced AS in ApoE(-/-)mice. Meanwhile, RSV decreased TMAO levels by inhibiting commensal microbial trimethylamine (TMA) production via gut microbiota remodeling in mice. Moreover, RSV increased levels of the genera Lactobacillus and Bifidobacterium, which increased the bile salt hydrolase activity, thereby enhancing bile acid (BA) deconjugation and fecal excretion in C57BL/6J and ApoE(-/-)mice. This was associated with a decrease in ileal BA content, repression of the enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) axis, and increased cholesterol 7a-hydroxylase (CYP7A1) expression and hepatic BA neosynthesis. An FXR antagonist had the same effect on FGF15 and CYP7A1 expression as RSV, while an FXR agonist abolished RSV-induced alterations in FGF15 and CYP7A1 expression. In mice treated with antibiotics, RSV neither decreased TMAO levels nor increased hepatic BA synthesis. Additionally, RSV-induced inhibition of TMAO-caused AS was also markedly abolished by antibiotics. In conclusion, RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling, and the BA neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis. IMPORTANCE: Recently, trimethylamine-N-oxide (TMAO) has been identified as a novel and independent risk factor for promoting atherosclerosis (AS) partially through inhibiting hepatic bile acid (BA) synthesis. The gut microbiota plays a key role in the pathophysiology of TMAO-induced AS. Resveratrol (RSV) is a natural phytoalexin with prebiotic benefits. A growing body of evidence supports the hypothesis that phenolic phytochemicals with poor bioavailability are possibly acting primarily through remodeling of the gut microbiota. The current study showed that RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling. And RSV-induced hepatic BA neosynthesis was partially mediated through downregulating the enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These results offer new insights into the mechanisms responsible for RSV's anti-AS effects and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases.
- In this study quercetin has been found to not only counter the effects of hypoxia in fat cells, but but actually to overcompensate those effects and improve fat tissue oxygenation
- Hypoxia is a key cause of cellulite and quercetin proves once again a valuable tool in the fight against cellulite, warranting it's use in anti-cellulite creams and also in nutritional supplements
- In addition quercetin has been found to boost the levels of irisin and PAI-1, which fight adipogenesis and fibrosis, respectively
- Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes.
- Abstract: Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes' gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications.
- Contrary to popular belief, fat cells are continuously produced and replaced by the body. It was previously known that fat cells, like or connective tissue cells, are derived by stem cells.
- However, new research has found that stem cells are identical to fibroblasts, what we call "collagen cells".
- So subdermis and dermis stem cells/fibroblasts are destined to remain fibroblasts and secrete collagen and elastin and keep our skin tight and elastic
- However, sugar, excess calories, excess estrogen and sedentary living make those stem cells / collagen cells "go astray" and become adipocytes (fat cells) in order to store the excess calories we accumulate
- As more and more collagen cells are replaced by fat cells our skin becomes looser and develops cellulite
- In a nutshell, we are naturally made to be slim and firm - overweight, obesity, loose skin and cellulite are solely of our own making.
- Source: Fibroblasts and Mesenchymal Stromal/Stem Cells Are Phenotypically Indistinguishable.
- Abstract: BACKGROUND/AIMS: Human mesenchymal stromal/stem cells (MSCs), derived from many different tissues, are characterized by a fibroblast-like morphology, the expression of certain cell surface markers and their ability to differentiate into adipocytes, chondrocytes and osteoblasts. A number of studies have shown that MSCs share many characteristics with fibroblasts; however, there is no well-defined set of phenotypic characteristics that could distinguish between these 2 types of cells. METHODS: We used 4 well-established human fibroblast strains from 3 different tissue sources and several human MSC strains from 2 different tissue sources to compare the phenotypic and immunological characteristics of these cells. RESULTS: Fibroblast strains had a similar morphology to MSCs, expressed the same cell surface markers as MSCs and could also differentiate into adipocytes, chondrocytes and osteoblasts. Also, similar to MSCs, these fibroblasts were capable of suppressing T cell proliferation and modulating the immunophenotype of macrophages. We also show that MSCs deposit extracellular matrices of collagen type I and fibronectin, and express FSP1 in patterns similar to fibroblasts. CONCLUSIONS: Based on currently accepted definitions for cultured human MSCs and fibroblasts, we could not find any immunophenotypic property that could make a characteristic distinction between MSCs and fibroblasts.
You cannot burn cellulite fat from a particular area with exercise alone
Exercise alone cannot lead to cellulite reduction in any particular area of the body (spot cellulite reduction). During exercise, the body decides where to draw fat from according to your genetic inheritance, lifestyle and hormones. In most women, fat on the thighs and butt (including cellulite fat) are the last places from where the body removes fat during exercise. This is because: fat cells in those areas have naturally occurring chemicals that can be described as metabolic brakes which ensure fat release during exercise or when dieting is kept at a minimum; and because the "cellulite tissues" have reduced circulation, and as a result they receive less lipolytic agents from the bloodstream (such as adrenaline) during exercise than other tissues.
But you can focus the effects of exercise by combining it with a strong cellulite treatment or cream
Therefore you can maximise the effectiveness of cellulite on a particular cellulite area by taking one or both of the following measures: you can block those metabolic brakes (alpha-2 adrenoreceptors and phosphodiesterases, among others) with a good cellulite cream that contains the right ingredients (alpha-2 adrenoreceptor inhibitors and phosphodiesterase inhibitors, respectively); you can increase circulation deep in the cellulite tissues during exercise with a suitable cellulite cream - or immediately before/after exercise with a strong anti-cellulite treatment that significantly increases circulation.
Examples of cellulite treatments that maximise the effects of exercise when applied before or after exercise
Any cellulite treatment that significantly increases circulation can be used immediately before or immediately after exercise, in order to maximise it's effectiveness on a specific cellulite area. The best examples are cellulite-specific massage, pressotherapy, high-power radiofrequency, high-power ultrasound and vacuum treatments. High intensive monopolar radiofrequency stands out as an anti-cellulite treatment, as it provides both significant skin firming and significantly increased circulation.
Cellulite cream ingredients that maximise the effects of exercise when applied before and after exercise
Two common alpha-2 adrenoreceptors are golden chamomile extract and the herbal extract yohimbine. An examples of phosphodiesterase inhibitor is caffeine. In addition to inhibitors, a good cellulite cream should also contain fat release stimulators, such as forskolin, and circulation enhancers such as the horse chestnut extract escin, the butcher’s broom extract ruscogenin etc.
These are some of the many anti-cellulite cream ingredients that can be used together with vigorous exercise to maximise and focus the effect of exercise where the cellulite cream is applied. Needless to say that a cellulite cream that is more concentrated and contains many different active ingredients will have more effectiveness than one with a low concentration of a couple of active ingredients.
The effect of a cellulite cream combined with exercise is more subdued than that of a cellulite treatment combined with exercise. However, given that an one-month supply of a quality anti-cellulite cream costs roughly the same as a single anti-cellulite treatment, cellulite creams are is a very cost-efficient solution. Furthermore, if you exercise very often you can further enhance the effectiveness and efficiency of the cream.
Cellulite treatments and creams cannot be used with low intensity exercise for spot cellulite reduction
This combination of cellulite creams and treatments with exercise is only effective when vigorous types of exercise are performed, such as interval training, fast running, spinning classes, fast cycling, or when playing vigorous sports such as basketball, football, netball etc. Unfortunately, light, slow exercise - such as Yoga, Pilates, slow walking and slow running - is not expected to provide any significant results, due to the low amount of adrenaline and noradrenaline released during such activities.
This is because, at low adrenaline levels (low intensity exercise) fat cells stop releasing fat after about 20 minutes of exercise. After that time, whatever fat is to be burned during exercise originates from the liver or from fat stored in the muscles - not from fat cells. As a result, low intensity exercise can not boost the effectiveness of the treatment or cream, because it can not stimulate the release of significant amounts of fat. All in all, low intensity exercise is better than nothing, but if you really want to reduce cellulite fast you should opt for high intensity exercise or sports.
[Safety note: always check with your doctor if you are unsure about your ability to safely perform vigorous exercise]Read More
The "fat zone training" myth debunked
Popular wisdom (straight from the 70's) has it that low intensity exercise is the best exercise for fat loss (and consequently cellulite reduction) because fat is utilised more than carbohydrates when performing slow, low intensity exercise. This is represented as the "fat zone" training intensity range in most cardiovascular equipment found in gyms. Unfortunately, although "fat calories" comprise a larger percentage of the total calories burned when performing low intensity exercise, the total amount of those calories is very low, in comparison to high intensity exercise.
In contrast, high intensity exercise "burns" much more calories per amount of time, even though carbohydrates are utilised at a higher rate than fat. Given that excessive carbohydrates are turned into fat and stored in fat cells (including cellulite fat cells), it doesn't really make sense to burn a small amount of "fat calories" with low intensity exercise, when you can burn a large amount of "carb calories" with high intensity exercise.
How does walking compare to running in terms of calorie burning and cellulite reduction
Practically this means that instead of spending two hours walking moderately at (3 mph) in order to burn a total of 390 calories, you are better off if you run moderately (at 6 mph) for one hour and burn 590 calories (data for an adult woman weighing 130lbs). Or, if you are fit enough, you can burn 885 calories in one hour of running at 9 mph - this is more than twice the fat burned when walking for two hours!
Or, to put it the other way round, you only need to run moderately (at 6 mph) for 39' minutes in order to achieve the same fat burned when moderately walking of 2 hours. Even better, you can run fast (at 9 mph) for only 26' minutes and still burn the same amount of calories that you would normally burn if you walked moderately (at 3 mph) for two hours. Given that nobody has enough time for exercise these days, the fast running solution seems to make much more sense than the moderate walking one.
In addition to immediate fat loss during the running session, fast running will boost overall metabolism after exercise to a much higher extent than walking, so you will lose fat when you sleep, in addition to losing fat when you run. So much for the fat burning zone and those outdated tables on the cardiovascular gym equipment! The truth is that, just like cars, the human body burns more fuel at higher speeds.
Pilates, Yoga, slow walking and leisurely swimming are a waste of time when it comes to cellulite reduction
Examples of low intensity exercise that does nothing or very little to reduce fat and cellulite include Pilates, Yoga, slow swimming, slow walking and similar activities. Some more intensive forms of Yoga and Pilates, such as Ashtanga Yoga and "Power Pilates" or "Hard Core Pilates" can help you burn calories faster than the plain varieties, but still they cannot compare to high intensity exercise for fat and cellulite reduction. Examples of high intensity exercise that works wonders for cellulite are fast running, fast swimming, fast cycling, spinning classes, circuits, interval training or sports such as basketball, netball, football, water polo etc.
The effect of exercise intensity on fat cells
Although it sounds counterintuitive, research has shown time and again that low intensity exercise stimulates the release of fat from the fat cells during exercise for only 20 minutes. After that time, whatever fat is to be burned during exercise originates from the liver or from fat stored in the muscles - not from fat cells. This may be of significance if you are trying to focus the effect of exercise on a specific body part by combining exercise with a suitable anti-cellulite treatment or cream (spot cellulite reduction).
In other words, if you are trying to burn local fat with the combination of low intensity exercise and an anti-cellulite treatment/cream applied immediately before or after exercise, then the fact is that low intensity exercise will not boost the effectiveness of the treatment or cream. All in all, low intensity exercise is better than nothing, but if you really want to reduce cellulite fast you should better opt for high intensity exercise or sports.
[Safety note: always check with your doctor if you are unsure about your ability to safely perform vigorous exercise]Read More
- Source: Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids
- Abstract: The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella's bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.