Loss of Adipose Fatty Acid Oxidation Does Not Potentiate Obesity at Thermoneutrality

被引:42
作者
Lee, Jieun [1 ,4 ]
Choi, Joseph [1 ,4 ]
Aja, Susan [2 ,4 ]
Scafidi, Susanna [3 ]
Wolfgang, Michael J. [1 ,4 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Ctr Metab & Obes Res, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
DIET-INDUCED OBESITY; BLOOD SPOTS; PPAR-ALPHA; BROWN; MICE; THERMOGENESIS; STRESS; RESISTANCE; FGF21; INFLAMMATION;
D O I
10.1016/j.celrep.2016.01.029
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ambient temperature affects energy intake and expenditure to maintain homeostasis in a continuously fluctuating environment. Here, mice with an adipose-specific defect in fatty acid oxidation (Cpt2A(-/-)) were subjected to varying temperatures to determine the role of adipose bioenergetics in environmental adaptation and body weight regulation. Microarray analysis of mice acclimatized to thermoneutrality revealed that Cpt2A(-/-) interscapular brown adipose tissue (BAT) failed to induce the expression of thermogenic genes such as Ucp1 and Pgc1a in response to adrenergic stimulation, and increasing ambient temperature exacerbated these defects. Furthermore, thermoneutral housing induced mtDNA stress in Cpt2A(-/-) BAT and ultimately resulted in a loss of interscapular BAT. Although the loss of adipose fatty acid oxidation resulted in clear molecular, cellular, and physiologic deficits in BAT, body weight gain and glucose tolerance were similar in control and Cpt2A(-/-) mice in response to a high-fat diet, even when mice were housed at thermoneutrality.
引用
收藏
页码:1308 / 1316
页数:9
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