8,229
Views
85
CrossRef citations to date
0
Altmetric
Review

Fatty acid metabolism and the basis of brown adipose tissue function

, , , , &
Pages 98-118 | Received 13 Aug 2015, Accepted 12 Nov 2015, Published online: 02 Mar 2016
 

ABSTRACT

Obesity has reached epidemic proportions, leading to severe associated pathologies such as insulin resistance, cardiovascular disease, cancer and type 2 diabetes. Adipose tissue has become crucial due to its involvement in the pathogenesis of obesity-induced insulin resistance, and traditionally white adipose tissue has captured the most attention. However in the last decade the presence and activity of heat-generating brown adipose tissue (BAT) in adult humans has been rediscovered. BAT decreases with age and in obese and diabetic patients. It has thus attracted strong scientific interest, and any strategy to increase its mass or activity might lead to new therapeutic approaches to obesity and associated metabolic diseases. In this review we highlight the mechanisms of fatty acid uptake, trafficking and oxidation in brown fat thermogenesis. We focus on BAT's morphological and functional characteristics and fatty acid synthesis, storage, oxidation and use as a source of energy.

Abbreviations

AC=

adenyl cyclase

ACC=

acetyl-CoA carboxylase

AMPK=

AMP-dependent protein kinase

ATG=

autophagy-related protein

ATGL=

adipose triglyceride lipase

BAT=

brown adipose tissue

BMP8b=

bone morphogenetic protein 8b

cAMP=

cyclic AMP

CIDEA=

cell death-inducing DNA fragmentation factor-α-like effector A

CGI-58=

comparative gene identification-58

CNS=

central nervous system

CPT=

carnitine palmitoyltransferase

DG=

diacylglycerol

DIO2=

type 2 iodothyronine deiodinase

ELOVL=

elongation of very long chain FA

ER=

endoplasmic reticulum

FA=

fatty acid

FAO=

fatty acid oxidation

FFA=

free fatty acids

FGF21=

fibroblast growth factor 21

G0S2=

G0/G1 switch gene 2

GPCRs=

G-protein-coupled receptors

HFD=

high-fat diet

HSL=

hormone-sensitive lipase

IGF-1=

insulin-like growth factor I

IL-1β=

interleukin-1β

IL-6=

interleukin-6

KO=

knockout

LAL=

lysosomal acid lipase

MEFs=

primary mouse fibroblasts

MG=

monoacylglycerol

MGL=

monoacylglycerol lipase

Myf5+=

myogenic factor 5-positive

iPLA2ζ=

calcium-independent phospholipase A2 ζ

PGC1α=

peroxisome proliferator activated receptor gamma coactivator 1 alpha

PKA=

protein kinase A

PKB=

protein kinase B

PRDM16=

PR domain-containing 16

pRb=

retinoblastoma protein

RIP140=

receptor interacting protein 140

TG=

triglyceride

TNFα=

tumor necrosis factor α

UCP1=

uncoupling protein-1

WAT=

white adipose tissue

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgment

We thank Robin Rycroft for valuable assistance in the preparation of the English manuscript.

Funding

This work was supported by the Ministry of Spain (SAF2013-45887-R to LH, SAF2014-52223-C2-1-R to DS (grant cofounded by Fondos Europeos de Desarrollo Regional de la Unión Europea (FEDER)) and doctoral fellowship to JFM), by the Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN) (Grant CB06/03/0001 to DS), by Generalitat de Catalunya (2014SGR465 to DS), and by the European Foundation for the Study of Diabetes (EFSD)/Janssen-Rising Star and L'Oréal-UNESCO “For Women in Science” research fellowships to LH. MW is a recipient of the Ciência sem Fronteiras-CNPq fellowship (237976/2012-9).