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Thioesterase superfamily member 1 suppresses cold thermogenesis by limiting the oxidation of lipid droplet-derived fatty acids in brown adipose tissue.

Authors: Okada, Kosuke  LeClair, Katherine B  Zhang, Yongzhao  Li, Yingxia  Ozdemir, Cafer  Krisko, Tibor I  Hagen, Susan J  Betensky, Rebecca A  Banks, Alexander S  Cohen, David E 
Citation: Okada K, etal., Mol Metab. 2016 Feb 23;5(5):340-351. doi: 10.1016/j.molmet.2016.02.002. eCollection 2016 May.
Pubmed: (View Article at PubMed) PMID:27110486
DOI: Full-text: DOI:10.1016/j.molmet.2016.02.002


OBJECTIVE: Non-shivering thermogenesis in brown adipose tissue (BAT) plays a central role in energy homeostasis. Thioesterase superfamily member 1 (Them1), a BAT-enriched long chain fatty acyl-CoA thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Them1 (-/-) mice exhibit increased energy expenditure and resistance to diet-induced obesity and diabetes, but the mechanistic contribution of Them1 to the regulation of cold thermogenesis remains unknown.
METHODS: Them1 (-/-) and Them1 (+/+) mice were subjected to continuous metabolic monitoring to quantify the effects of ambient temperatures ranging from thermoneutrality (30 °C) to cold (4 °C) on energy expenditure, core body temperature, physical activity and food intake. The effects of Them1 expression on O2 consumption rates, thermogenic gene expression and lipolytic protein activation were determined ex vivo in BAT and in primary brown adipocytes.
RESULTS: Them1 suppressed thermogenesis in mice even in the setting of ongoing cold exposure. Without affecting thermogenic gene transcription, Them1 reduced O2 consumption rates in both isolated BAT and primary brown adipocytes. This was attributable to decreased mitochondrial oxidation of endogenous but not exogenous fatty acids.
CONCLUSIONS: These results show that Them1 may act as a break on uncontrolled heat production and limit the extent of energy expenditure. Pharmacologic inhibition of Them1 could provide a targeted strategy for the management of metabolic disorders via activation of brown fat.

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RGD Object Information
RGD ID: 13673863
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.