title: Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio.
abstract: White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin-dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Bairwa
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Rajapurohitam
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Xiaohong Tracey
authors.initials: XT
authors.lastname: Gan
authors.affiliation: Alberta Diabetes and Mazankowski Heart Institutes, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
authors.forename: Rabban
authors.initials: R
authors.lastname: Mangat
authors.affiliation: Alberta Diabetes and Mazankowski Heart Institutes, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Proctor
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Morris
authors.initials: M
authors.lastname: Karmazyn
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D052242:Adiponectin; D017077:Culture Media, Conditioned; D019332:Endothelin-1; D020738:Leptin; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases