Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Investigating the molecular basis and therapeutic potential of the HO-1 adiponectin axis (#89)

Mengliu Yang 1 , Choaping Ng 1 , Jingjing He 1 , Sahar Keshvari 1 , Johanna L Barclay 1 , Jon P Whitehead 1
  1. Mater Research Institute, University of Queensland, 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. A recent suit of literature indicates that Heme Oxygenase 1 (HO-1) could be beneficial to this cause, with many proclaiming the existence of an HO-1 Adiponectin axis. Our team has now performed a thorough investigation of this intriguing paradigm. Using an in vitro model of human adipocyte cell strain and primary human adipocytes, coupled with a comprehensive array of pharmaceutical (cobalt protoporphyrin (CoPP) or hemin) and genetic modulators of HO-1, we have shown that there is no direct HO-1 Adiponectin axis in human adipocytes1.  However, we have demonstrated that systemic CoPP –induced HO-1 in diet-induced obese mice can increase circulating adiponectin, concurrent with decreased food intake, decreased body weight gain, increased insulin sensitivity, decreased liver steatosis and reduced adipocyte size. Importantly only the effect on adiponectin was blunted when mice were co-treated with an inhibitor of HO-1 activity (SnMP).   Collectively these in vivo studies indicate that systemic induction of HO-1 by CoPP can lead to increased circulating adiponectin, concurrent with important HO-1-independent improvements in cardiometabolic metabolic health. Therefore, CoPP may hold promise as a therapeutic for the treatment of obesity and obesity-related disease.

  1. 1. M. Yang, M. Kimura, C. Ng, J. He, S. Keshvari, F.J. Rose, J.L. Barclay, J. P. Whitehead, Induction of heme-oxygenase-1 (HO-1) does not enhance adiponectin production in human adipocytes: Evidence against a direct HO-1 - Adiponectin axis. Mol Cell Endocrinol. (2015) Sep 15;413:209-16.