Dataset Information

Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6.

ABSTRACT: Although many transcriptional pathways regulating BAT have been identified, the role of lipid biosynthetic enzymes in thermogenesis has been less investigated. Whereas cold exposure causes changes in the fatty acid composition of BAT, the functional consequences of this remains relatively unexplored. In this study, we demonstrate that the enzyme Elongation of Very Long Chain fatty acids 6 (Elovl6) is necessary for the thermogenic action of BAT. Elovl6 is responsible for converting C16 non-essential fatty acids into C18 species. Loss of Elovl6 does not modulate traditional BAT markers; instead, it causes reduced expression of mitochondrial electron transport chain components and lower BAT thermogenic capacity. The reduction in BAT activity appears to be counteracted by increased beiging of scWAT. When beige fat is disabled by thermoneutrality or aging, Elovl6 KO mice gain weight and have increased scWAT mass and impaired carbohydrate metabolism. Overall, our study suggests fatty acid chain length is important for BAT function.

SUBMITTER: Tan CY

PROVIDER: S-EPMC4688035 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6.

Tan Chong Yew CY Virtue Samuel S Bidault Guillaume G Dale Martin M Hagen Rachel R Griffin Julian L JL Vidal-Puig Antonio A

Cell reports 20151125 10

Although many transcriptional pathways regulating BAT have been identified, the role of lipid biosynthetic enzymes in thermogenesis has been less investigated. Whereas cold exposure causes changes in the fatty acid composition of BAT, the functional consequences of this remains relatively unexplored. In this study, we demonstrate that the enzyme Elongation of Very Long Chain fatty acids 6 (Elovl6) is necessary for the thermogenic action of BAT. Elovl6 is responsible for converting C16 non-essent ...[more]

PMID: 26628376

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Project description:UnlabelledLow-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets.MethodsMale Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks. The diets had the following macronutrient composition (% metabolizable energy: carbohydrates, fat, protein): control (64.3/16.7/19), LC-HF-low protein (LC-HF-LP, 1.7/92.8/5.5), LC-HF-normal-protein (LC-HF-NP, 2.2/78.7/19.1), and a high fat diet with carbohydrates ("high fat", 19.4/61.9/18.7).ResultsBody weight gain was reduced in all pair-fed experimental groups as compared to rats fed the control diet, with more pronounced effect in rats on LC-HF diets than on the high fat diet with carbohydrates. High fat diets increased expression of PGC1α and ADRB3 in BAT indicating higher SNS outflow. However, UCP1 mRNA expression and expression of UCP1 assessed by immunohistochemistry was not different between diet groups. In accordance, analysis of mitochondrial function in-vitro by extracellular flux analyser (Seahorse Bioscience) and measurement of inducible thermogenesis in vivo (primary endpoint), explored by indirect calorimetry following norepinephrine injection, did not show significant differences between groups. Histology of BAT revealed increased lipid droplet size in rats fed the high-fat diet and both LC-HF diets.ConclusionAll experimental diets upregulated expression of genes which are indicative for increased BAT activity. However, the functional measurements in vivo revealed no increase of inducible BAT thermogenesis. This indicates that lower body weight gain with LC-HF diets and a high fat diet in a pair-feeding setting is not caused by increased adaptive thermogenesis in BAT.

Dataset Information

Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6.

Publications

Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6.

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