Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6.

Chong Yew Tan,Rachel Hagen,Julian L Griffin,Guillaume Bidault,Antonio Vidal-Puig,Martin Dale,Samuel Virtue

doi:10.1016/j.celrep.2015.11.004

Abstract

SummaryAlthough 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.

Highlights

Brown adipose tissue (BAT) is responsible for heat generation, a process that occurs due to the uncoupling of electron transport from ATP synthesis by uncoupling protein 1 (UCP1)
We initially investigated the changes in fatty acid chain length in BAT and other metabolically relevant organs in response to cold acclimation
We measured the expression profile of Elovl6 across multiple tissues at room temperature and determined that, consistent with previous reports (Moon et al, 2001), the expression of Elovl6 was highest in BAT, followed by inguinal subcutaneous white adipose tissue (WAT), liver, and muscle, a sequence that mirrored the respective C18:C16 ratios of the tissues (Figure 1G)

Summary

Introduction

Brown adipose tissue (BAT) is responsible for heat generation, a process that occurs due to the uncoupling of electron transport from ATP synthesis by uncoupling protein 1 (UCP1). The most potent environmental factor regulating BAT is temperature. In response to an acute reduction in environmental temperature (cold exposure), BAT is immediately activated to produce heat. If an animal is maintained at a lower environmental temperature, BAT is recruited, increasing the thermogenic capacity of the animal. When the amount of BAT present matches the requirements of the new temperature, an animal is described as cold acclimated (Cannon and Nedergaard, 2004). The sympathetic nervous system (SNS) is, perhaps, the single most important factor controlling BAT activation and acclimation. In response to cold exposure, SNS tone to BAT increases causing both the activation of UCP1 and initiating a series of transcriptional changes that lead to BAT recruitment. While many transcriptional pathways regulating BAT recruitment have been identified, there has been less focus on the role of lipid metabolism within BAT, other than as a source of fuel (Bartelt et al, 2011)

Results

Discussion

Conclusion