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Updated: Sep 16, 2025

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
G proteins of the G12 family expressed by POMC neurons regulate key metabolic functions
Dhanush Haspula1, Zhenzhong Cui2, Srinivas Pittala1
1Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Abstract:
Proopiomelanocortin (POMC) neurons play a key role in maintaining glucose and energy homeostasis. POMC neurons express many heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors that are linked to different functional classes of G proteins. The potential role of G12/13 in regulating the function of central POMC neurons remains unknown. To address this question, we used a chemogenetic approach to selectively stimulate G12/13 signaling in POMC neurons. We found that receptor-mediated activation of G12/13 signaling in POMC neurons caused notable improvements in glucose homeostasis in lean and obese mice. Stimulation of G12/13 signaling in POMC neurons also enhanced the physiological actions of leptin. Studies with G12/13 knockout mice showed that G12/13 signaling in POMC neurons mediated the beneficial metabolic effects of lorcaserin, an appetite-suppressant drug that selectively activates serotonin 5-HT2C receptors. These findings indicate that G12/13-coupled receptors expressed by POMC neurons represent potential targets for advanced classes of antidiabetic and appetite-suppressant drugs.
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