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FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice
Hypothalamic “metabolic-sensing” neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ∼50% of these neurons responded to oleic acid (OA...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717873/ https://www.ncbi.nlm.nih.gov/pubmed/23557700 http://dx.doi.org/10.2337/db12-1689 |
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author | Le Foll, Christelle Dunn-Meynell, Ambrose Musatov, Serguei Magnan, Christophe Levin, Barry E. |
author_facet | Le Foll, Christelle Dunn-Meynell, Ambrose Musatov, Serguei Magnan, Christophe Levin, Barry E. |
author_sort | Le Foll, Christelle |
collection | PubMed |
description | Hypothalamic “metabolic-sensing” neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ∼50% of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36–depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a critical factor in both VMH neuronal FA sensing and the regulation of energy and glucose homeostasis. |
format | Online Article Text |
id | pubmed-3717873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-37178732014-08-01 FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice Le Foll, Christelle Dunn-Meynell, Ambrose Musatov, Serguei Magnan, Christophe Levin, Barry E. Diabetes Original Research Hypothalamic “metabolic-sensing” neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ∼50% of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36–depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a critical factor in both VMH neuronal FA sensing and the regulation of energy and glucose homeostasis. American Diabetes Association 2013-08 2013-07-17 /pmc/articles/PMC3717873/ /pubmed/23557700 http://dx.doi.org/10.2337/db12-1689 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Le Foll, Christelle Dunn-Meynell, Ambrose Musatov, Serguei Magnan, Christophe Levin, Barry E. FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice |
title | FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice |
title_full | FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice |
title_fullStr | FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice |
title_full_unstemmed | FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice |
title_short | FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice |
title_sort | fat/cd36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717873/ https://www.ncbi.nlm.nih.gov/pubmed/23557700 http://dx.doi.org/10.2337/db12-1689 |
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