Phosphoinositide 3-Kinase Is Integral for the Acute Activity of Leptin and Insulin in Male Arcuate NPY/AgRP Neurons

Journal of the Endocrine Society
Yiru HuangKevin W Williams

Abstract

Neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are part of a neuroendocrine feedback loop that regulates feeding behavior and glucose homeostasis. NPY/AgRP neurons sense peripheral signals (including the hormones leptin, insulin, and ghrelin) and integrate those signals with inputs from other brain regions. These inputs modify both long-term changes in gene transcription and acute changes in the electrical activity of these neurons, leading to a coordinated response to maintain energy and glucose homeostasis. However, the mechanisms by which the hormones insulin and leptin acutely modify the electrical activity of these neurons remain unclear. In this study, we show that loss of the phosphoinositide 3-kinase catalytic subunits p110α and p110β in AgRP neurons abrogates the leptin- and insulin-induced inhibition of AgRP neurons. Moreover, continual disruption of p110α and p110β in AgRP neurons results in increased weight gain. The increased adiposity was concomitant with a hypometabolic phenotype: decreased energy expenditure independent of changes in food intake. Deficiency of p110α and p110β in AgRP neurons also impaired glucose homeostasis and insulin sensitivity. In summa...Continue Reading

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Citations

Dec 7, 2018·British Journal of Pharmacology·Zhenyan HeKevin W Williams
Jan 9, 2019·Journal of Neuroendocrinology·David Garcia-GalianoCarol F Elias
Jan 3, 2019·Endocrinology·Anne R Bresnick, Jonathan M Backer
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Feb 19, 2021·Journal of Neuroendocrinology·Teppei Fujikawa
Sep 23, 2021·JCI Insight·Zhenyan HeKevin W Williams
Jul 2, 2020·Physiology & Behavior·Linh LieuKevin W Williams

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Methods Mentioned

BETA
nuclear magnetic resonance
fluorescence microscopy

Software Mentioned

ImageJ
pCLAMP

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