P110β in the ventromedial hypothalamus regulates glucose and energy metabolism
Autor: | Jose Donato, Charlotte E. Lee, Ki Woo Kim, Syann Lee, Carol F. Elias, Dong Min Shin, Yun Hee Choi, Dong Joo Yang, Teppei Fujikawa, Daisuke Kohno |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_treatment Clinical Biochemistry Hypothalamus lcsh:Medicine Adipose tissue Carbohydrate metabolism Steroidogenic Factor 1 Biochemistry Energy homeostasis Article lcsh:Biochemistry 03 medical and health sciences Mice 0302 clinical medicine medicine Animals lcsh:QD415-436 Obesity Molecular Biology PI3K/AKT/mTOR pathway In Situ Hybridization Mice Knockout Chemistry Insulin Leptin lcsh:R Metabolism Cell biology Experimental models of disease 030104 developmental biology Glucose 030220 oncology & carcinogenesis Molecular Medicine Energy Metabolism Neuroscience |
Zdroj: | Experimental & Molecular Medicine Experimental and Molecular Medicine, Vol 51, Iss 4, Pp 1-9 (2019) |
ISSN: | 2092-6413 1226-3613 |
Popis: | 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. Metabolism: Enzymatic subunit essential to brain’s glucose responses A particular subunit of a critical signaling enzyme is needed for neurons inside the brain’s hypothalamus to properly regulate energy metabolism. Ki Woo Kim from Yonsei University College of Dentistry, Seoul, South Korea, and colleagues explored the role that the PI3K enzyme plays in neurons of the ventromedial area toward the front of the hypothalamus, a region involved in regulating hunger and metabolism. Deleting a subunit of PI3K called p110β, which is needed for enzymatic function, made mice less responsive to insulin, the hormone that keeps blood sugar levels at healthy levels. As well as having abnormal glucose metabolism, the mice converted more brown fat, which burns energy, into white fat, which stores energy. They were also more susceptible to diet-induced obesity. The findings point toward p110β as a potential drug target for treating diabetes. |
Databáze: | OpenAIRE |
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