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Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice

Published on Apr 15, 2014in American Journal of Physiology-endocrinology and Metabolism4.125
· DOI :10.1152/ajpendo.00473.2013
Meritxell Rosell4
Estimated H-index: 4
(Imperial College London),
Myrsini Kaforou9
Estimated H-index: 9
(Imperial College London)
+ 14 AuthorsMark Christian31
Estimated H-index: 31
(Warw.: University of Warwick)
Abstract
Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a “brite” transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with “browning,” as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.
  • References (65)
  • Citations (154)
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References65
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#1Gregory GaichH-Index: 1
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Last. David E. MollerH-Index: 66
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Summary Fibroblast growth factor 21 (FGF21) is a recently discovered metabolic regulator. Exogenous FGF21 produces beneficial metabolic effects in animal models; however, the translation of these observations to humans has not been tested. Here, we studied the effects of LY2405319 (LY), a variant of FGF21, in a randomized, placebo-controlled, double-blind proof-of-concept trial in patients with obesity and type 2 diabetes. Patients received placebo or 3, 10, or 20 mg of LY daily for 28 days. LY ...
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#1Andrew Shore (Cardiff University)H-Index: 4
#2Angeliki Karamitri (French Institute of Health and Medical Research)H-Index: 9
Last. Michael A. Lomax (University of Nottingham)H-Index: 23
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Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and ...
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#1Matthias RosenwaldH-Index: 4
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Brown adipose cells contribute to body temperature maintenance by converting lipids and glucose into heat, and can be found in white adipose tissue. Wolfrum and colleagues find a population of cells in white adipose tissue that can adopt brown or white characteristics in response to cold.
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Brown adipose tissue (BAT) burns, rather than stores, energy and has thus been explored as a way to combat obesity. Aaron Cypess and his colleagues isolate neck fat from adult humans and show that BAT exists in this region, define its anatomical localization in the neck relative to white adipose tissue and demonstrate that it is functional.
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p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity
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The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was commonly believed to be the equivalent of the interscapular thermogenic organ of small mammals. This ...
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Failure of white adipose tissue to appropriately store excess metabolic substrate seems to underpin obesity-associated type 2 diabetes. Encouraging “browning” of white adipose has been suggested as a therapeutic strategy to help dispose of excess stored lipid and ameliorate the resulting insulin resistance. Genetic variation at the DNA locus encoding the novel proteolipid neuronatin has been associated with obesity, and we recently observed that neuronatin expression is reduced in subcutaneous a...
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