Abstract
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.
Highlights
Obesity and obesity-related metabolic diseases are major public health burdens[1]
Discussion the metabolic importance of Phosphoinositide 3-kinase (PI3K) has been shown in several tissues, little is known about its function in the hypothalamus[6,9,11]
We deleted the p110β isoform of PI3K from steroidogenic factor-1 (SF-1) neurons of the ventral medial nucleus of the hypothalamus (VMH)
Summary
Obesity and obesity-related metabolic diseases are major public health burdens[1]. The central nervous system (CNS) governs whole-body metabolism by sensing and responding to fluctuating levels of circulating cues, such as nutrients and hormones. The ventral medial nucleus of the hypothalamus (VMH) has been known since the early 1940s, to play a critical role in the regulation of glucose and energy balance[4,5]. The molecular blueprint underlying the VMH regulation of variant in proopiomelanocortin (POMC) and agoutirelated peptide (AgRP) neurons of the arcuate nucleus (ARC) of the hypothalamus[7,8,9]. These studies indicate that, at least in ARC neurons, p110β plays a greater role in the regulation of metabolism than does p110α. We investigated the role of p110β in the VMH in the regulation of glucose and energy metabolism
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