Phosphoinositide 3-kinase (PI3K) signaling in hypothalamic neurons integrates peripheral metabolic cues, including leptin and insulin, to coordinate systemic glucose and energy homeostasis. PI3K is composed of different subunits, each of which has several unique isoforms. However, the role of the PI3K subunits and isoforms in the ventromedial hypothalamus (VMH), a prominent site for the regulation of glucose and energy homeostasis, is unclear. Here we investigated the role of subunit p110β in steroidogenic factor-1 (SF-1) neurons of the VMH in the regulation of metabolism. Our data demonstrate that the deletion of p110β in SF-1 neurons disrupts glucose metabolism, rendering the mice insulin resistant. In addition, the deletion of p110β in SF-1 neurons leads to the whitening of brown adipose tissues and increased susceptibility to diet-induced obesity due to blunted energy expenditure. These results highlight a critical role for p110β in the regulation of glucose and energy homeostasis via VMH neurons.
Bibliographical noteFunding Information:
We thank Dr. Joel K. Elmquist (UT Southwestern Medical Center) for guidance and suggestions. We also thank Laura Brule, Min Kim, Danielle Lauzon, and Linh-An Cao for technical assistance and the Metabolic Phenotyping Core at the University of Texas Southwestern Medical Center (supported by PL1 DK081182 and UL1RR024923). Funding for these studies was provided to T.F. (Juvenile Diabetes Research Foundation postdoctoral fellowship 3-2011-405 and an American Heart Association Scientist Development Grant 14SDG17950008), C.F.E. (NIH grant R01HD061539), and K.W.K. (Korea Health Industry Development Institute HI17C0745 and the National Research Foundation NRF-2016R1C1B3012748 and NRF-2016R1A5A2008630).
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry