Işın Çakır, Colleen K Hadley, Pauline Lining Pan, Rushita A Bagchi, Masoud Ghamari-Langroudi, Danielle T Porter, Qiuyu Wang, Michael J Litt, Somnath Jana, Susan Hagen, Pil Lee, Andrew White, Jiandie D Lin, Timothy A McKinsey, Roger D Cone
The adipose tissue-derived hormone leptin can drive decreases in food intake while increasing energy expenditure. In diet-induced obesity, circulating leptin levels rise proportionally to adiposity. Despite this hyperleptinemia, rodents and humans with obesity maintain increased adiposity and are resistant to leptin's actions. Here we show that inhibitors of the cytosolic enzyme histone deacetylase 6 (HDAC6) act as potent leptin sensitizers and anti-obesity agents in diet-induced obese mice. Specifically, HDAC6 inhibitors, such as tubastatin A, reduce food intake, fat mass, hepatic steatosis and improve systemic glucose homeostasis in an HDAC6-dependent manner...
January 2022: Nature metabolism