This study investigated the role of pyruvate dehydrogenase kinase (PDK) in diet-induced obesity. Mice with PDK2 deficiency showed protection against diet-induced obesity, reduced adipose tissue weight and adipocyte size, and slightly improved insulin sensitivity. In 3T3-L1 preadipocytes, PDK1/2 expression increased during adipogenesis, with evidence of epigenetic induction. PDK1/2 played a critical role in adipocyte differentiation and lipid accumulation, linked to increased HIF1α and lactate production. Exogenous lactate promoted adipogenesis, and HIF1α inhibition abolished PDK1/2 overexpression-mediated adipogenesis. In human adipose tissue, PDK1/2 expression correlated positively with PPARγ and inversely with obesity. The study concludes that PDK1 and 2 are novel regulators of adipogenesis crucial in obesity.

Hyeon-Ji Kang, Byong-Keol Min, Won-Il Choi, Jae-Han Jeon, Dong Wook Kim, Sungmi Park, Yun-Kyung Lee, Hwa-jin Kim, Ju-Eun Byeon, Younghoon Go, Hye Jin Ham, Yong Hyun Jeon, Mi-Jin Kim, Jung Yi Lee, Adam R. Wende, Sung Hee Choi, Robert A. Harris, In-Kyu Lee