Why lack of oxygen leads to fat accumulation and cellulite

  • Research published in the journal Diabetes has shown that enhanced oxygenation leads to lipolysis (fat release from fat cells). This intuitively makes sense, because more oxygen means more blood circulation, which would indicate physical exertion and thus the need for the release of stored fuel, including store fat..
  • Specifically, scientists have found that the enzyme PHD2 senses oxygen levels and boosts adipocyte lipolysis (fat release from fat cells) by inhibiting the protein HIF-1 (hypoxia-inducible factor-1)
  • Conversely, it was found that inactivation of PHD2 (i.e. inactivation of oxygen sensing by fat cells), leads to the breakdown of the lipolytic enzymes hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)
  • So in summary, for lipolysis to occur fat cells must sense the presence of oxygen. If they cannot sense oxygen (via PHD2) then they shut down the breakdown of fat. If they can sense oxygen then they allow lipolysis to occur.
  • The researchers conclude that by inhibiting PHD2 we may be able to treat lipodystrophy (i.e. the impaired growth of fat cells), but most importantly that by boosting PHD2 we may be able to treat overweight and obesity.
  • However, the most important take-home message of this paper is that fat tissue oxygenation will lead to fat release from fat cells. As a consequence, anything that boosts fat tissue circulation - and therefore oxygenation - including exercise, circulation-boosting foods and supplements and treatments, and circulation-enhancing anti-cellulite cream active ingredients, can all help boost lipolysis and reduce adiposity and cellulite.
  • On the other hand, this is another reminder that lack of oxygen, either due to poor circulation (because of lack of physical activity or even due to tissue compression), can lead to fat accumulation and cellulite.
  • Source: Adipocyte Pseudohypoxia Suppresses Lipolysis and Facilitates Benign Adipose Tissue Expansion.
  • Abstract: Prolyl hydroxylase enzymes (PHDs) sense cellular oxygen upstream of hypoxia-inducible factor (HIF) signaling, leading to HIF degradation in normoxic conditions. In this study, we demonstrate that adipose PHD2 inhibition plays a key role in the suppression of adipocyte lipolysis. Adipose Phd2 gene ablation in mice enhanced adiposity, with a parallel increase in adipose vascularization associated with reduced circulating nonesterified fatty acid levels and normal glucose homeostasis. Phd2 gene-depleted adipocytes exhibited lower basal lipolysis in normoxia and reduced β-adrenergic-stimulated lipolysis in both normoxia and hypoxia. A selective PHD inhibitor suppressed lipolysis in murine and human adipocytes in vitro and in vivo in mice. PHD2 genetic ablation and pharmacological inhibition attenuated protein levels of the key lipolytic effectors hormone-sensitive lipase and adipose triglyceride lipase (ATGL), suggesting a link between adipocyte oxygen sensing and fatty acid release. PHD2 mRNA levels correlated positively with mRNA levels of AB-hydrolase domain containing-5, an activator of ATGL, and negatively with mRNA levels of lipid droplet proteins, perilipin, and TIP47 in human subcutaneous adipose tissue. Therapeutic pseudohypoxia caused by PHD2 inhibition in adipocytes blunts lipolysis and promotes benign adipose tissue expansion and may have therapeutic applications in obesity or lipodystrophy.