Role of mTORC2 in biphasic regulation of brown fat metabolism in response to mild and severe cold
| Autor: | Esther Paulo, Catherine E. Gleason, Yixuan Wu, Ajay Chawla, Seunghwan Lee, Biao Wang, David A. Pearce, Prasanna K.R. Allu, Gavin Situ, Ambre M. Bertholet, Bidisha Saha |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
SNS sympathetic nervous system Male TBP TATA-binding protein Medical and Health Sciences Biochemistry MEF murine embryo fibroblast Mice Adipose Tissue Brown Brown adipose tissue GTP-Binding Protein alpha Subunits Gs Uncoupling protein Beta oxidation Uncoupling Protein 1 Mice Knockout Chemistry Thermogenesis thermogenesis Biological Sciences Thermogenin Cell biology Cold Temperature medicine.anatomical_structure Heat generation Lipogenesis mTOR Research Article Signal Transduction Biochemistry & Molecular Biology UCP1 adipocytes DNL de novo lipogenesis Mechanistic Target of Rapamycin Complex 2 03 medical and health sciences Receptors Adrenergic beta medicine Chromogranins Animals Molecular Biology lipogenesis PEG polyethylene glycol 030102 biochemistry & molecular biology Catabolism iBAT interscapular brown adipose tissue brown adipose tissue UCP1 uncoupling protein-1 Cell Biology cold BAT brown adipose tissue Mice Inbred C57BL 030104 developmental biology Chemical Sciences gene expression PKA protein kinase A |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Nonshivering thermogenesis is essential for mammals to maintain body temperature. According to the canonical view, temperature is sensed by cutaneous thermoreceptors and nerve impulses transmitted to the hypothalamus, which generates sympathetic signals to ß-adrenergic receptors in brown adipocytes. The energy for heat generation is primarily provided by the oxidation of fatty acids derived from triglyceride hydrolysis and cellular uptake. Fatty acids also activate the uncoupling protein, UCP1, which creates a proton leak that uncouples mitochondrial oxidative phosphorylation from ATP production, resulting in energy dissipation as heat. Recent evidence supports the idea that in response to mild cold, ß-adrenergic signals stimulate not only lipolysis and fatty acid oxidation, but also act through the mTORC2-Akt signaling module to stimulate de novo lipogenesis. This opposing anabolic effect is thought to maintain lipid fuel stores during increased catabolism. We show here, using brown fat-specific Gs-alpha knockout mice and cultured adipocytes that, unlike mild cold, severe cold directly cools brown fat and bypasses ß-adrenergic signaling to inhibit mTORC2. This cell-autonomous effect both inhibits lipogenesis and augments UCP1 expression to enhance thermogenesis. These findings suggest a novel mechanism for overriding ß-adrenergic-stimulated anabolic activities while augmenting catabolic activities to resolve the homeostatic crisis presented by severe cold. |
| Databáze: | OpenAIRE |
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