Effects of Different Oxygen Concentrations on Human Differentiated Preadipocytes Lipogenic and Lipolytic functions

Abstract

ContextFat stored in white adipose tissue is the human body's largest energy reservoir. Adipocytes, the predominant cell population in white adipose tissue, play a central role in the clearance of circulating triglyceride (TG) and the delivery of fatty acids for use by peripheral tissues. Impaired regulation of adipose tissue functions is thought to stimulate lipid deposition in non‐adipose tissues, inducing lipotoxic response and the development of metabolic disorders. During weight gain, adipocytes expand in size, decreasing adipose tissue capillary density and creating areas characterized by excessively low oxygen concentrations (hypoxia). It is not clear how hypoxia modulates adipose tissue TG clearance and fatty acid delivery.ObjectiveThe purpose of this study was to investigate the effects of different hypoxia concentrations on lipogenic (store TG) and lipolytic functions (deliver fatty acids) of human differentiated preadipocytes.MethodsDifferentiated human preadipocytes were exposed to different oxygen concentrations (3%, 10%, and 21%) either during differentiation (14d, continuous exposure) or acutely for 24h after differentiation (acute exposure). Gene expression of lipogenic enzymes and regulating factors will be determined by real‐time PCR. Lipoprotein lipase (LPL) activity was measured using the EnzChek Lipase Substrate and lipolytic rate was determined by measuring glycerol release over 3 hours.ResultsIn differentiated human preadipocytes, a dose‐dependent reduction in LPL activity was observed in both acute and continuous hypoxia (6‐fold reduction under 3% O2 p<0.001, 2‐fold reduction under 10% O2, p<0.05, compared to 21% O2). Basal lipolysis was significantly higher during acute hypoxia (3%) session (p<0.05). No differences in isoproterenol‐ and epinephrine‐stimulated lipolytic responses were observed in subcutaneous abdominal preadipocytes between normoxia and acute hypoxia (3%).ConclusionsThese preliminary results suggest that acute and continuous hypoxia strongly inhibits LPL activity and increases basal lipolysis. These observation supports the hypothesis that hypoxia may adversely affect adipose tissue storage functions, which could in turn contribute to ectopic fat storage, lipotoxicity and a greater prevalence of metabolic disorders in individual with excess adiposity.Support or Funding InformationThis study was supported by the Natural Sciences and Engineering Research Council of Canada as well as the University of Ottawa.