Adipocyte hypertrophy and hyperplasia is a hallmark of obesity, and treatments that induce the oxidation of lipid stores may represent a potential therapy. When stimulated by cold or beta-adrenergic agonists, adipocytes in inguinal white adipose tissue (iWAT) can convert to beige cells, which resemble brown adipocytes. This process can reduce body weight in rodents and improve glucose homeostasis through increased Ucp1-dependent lipid oxidation. 14-3-3?, a molecular scaffold we found to be essential for adipogenesis, regulates the enzymatic activities of tryptophan and tyrosine hydroxylases, both of which influence beiging. Thus, the aim of the current study is to investigate whether 14-3-3? influences the beiging process. Compared to control mice, acute (3 hr) and chronic (72 hr) cold (4 C) exposure in male transgenic mice over-expressing 14-3-3? led to improved cold tolerance due to significantly increased Ucp1 mRNA and protein in iWAT. Following chronic exposure, they were also able to maintain their body weight by increasing their food intake. Consistent with these data, analysis of adipocyte area revealed a decrease in the size of inguinal adipocytes in transgenic mice, suggesting increased lipid oxidation. In contrast, gonadal adipocytes were larger in transgenic mice, which may explain their ability to maintain their body weight. Systemic 14-3-3? knockout mice had significantly lower levels of Ucp1 mRNA in iWAT and BAT but did not display differences in tolerance to acute cold. Depletion of 14-3-3? by siRNA in brown adipocytes did not impair isoproterenol-mediated induction of Ucp1 mRNA, suggesting that 14-3-3? is not required for Ucp1 expression in this cell type. In future studies, we will examine if 14-3-3? influences the responsiveness of iWAT to chronic β-adrenergic stimuli and assess the impact of 14-3-3? overexpression in brown adipocyte function. Collectively, our results point to a novel role of 14-3-3? in the beiging of inguinal adipocytes and increase our understanding of how beiging is regulated.


K. Diallo: None. G.E. Lim: None.


Canadian Institutes of Health Research; Fonds de la recherche en santé du Québec; Centre de recherche du CHUM; Montreal Diabetes Research Center

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