Oral Presentation Australian & New Zealand Obesity Society 2014 Annual Scientific Meeting

Induction of heme-oxygenase (HO-1) does not enhance adiponectin production in human adipocytes: evidence against an HO-1/adiponectin axis (#72)

Mengliu Yang 1 , Masaki Kimura 1 , Choaping Ng 1 , Jingjing He 1 , Felicity M Rose 1 , Johanna L Barclay 1 , Jon P Whitehead 1
  1. Mater Research Institute, Wooloongabba, QLD, Australia

Adiponectin is a salutary hormone produced by adipocytes, and hypoadiponectinemia is implicated in the aetiology of obesity-related cardiometabolic diseases, making therapeutic strategies to increase adiponectin attractive. Emerging evidence, predominantly from preclinical studies, suggests that induction of HO-1 increases adiponectin production. The main aim of this study was to determine whether induction of HO-1 enhanced adiponectin production from adipocytes.

Treatment of mature human SGBS adipocytes with cobalt protoporphyrin (CoPP) for 24-48 hours promoted a dose-dependent increase in HO-1 (mRNA and protein) without affecting adiponectin secretion.  The pro-inflammatory cytokine TNFα is increased in obesity and involved in the progression of obesity-related diseases. Treatment of adipocytes with TNFα reduced adiponectin secretion and increased expression and/or secretion of pro-inflammatory cytokines (IL-6, TNFα & MCP-1) and expression of an ER stress marker (sXBP-1). HO-1 induction failed to reverse these effects. 

Further investigations exploring the effects of chronic (14 day) CoPP or Hemin treatment on adipogenesis revealed a dose-dependent inhibition of differentiation indicated by decreased lipid droplet accumulation, decreased adiponectin secretion, downregulation of key genes necessary for adipogenesis and adipocyte function (Pparg, AdipoQ and Glut4), increased IL-6 secretion and decreased insulin-stimulated glucose uptake.

Our results demonstrate that: acute induction of HO-1 does not enhance adiponectin secretion in mature human adipocytes; chronic HO-1 induction interferes with differentiation and subsequent adipocyte function. Collectively, these findings argue against a direct HO-1/adiponectin axis, and do not support a beneficial role for HO-1 in adipocyte development or function.