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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).