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

• Fatty acid oxidation (FAO) is required for the induction of Ucp1 and Pgc1α in BAT
• Increasing ambient temperature potentiates defects in FAO-deficient BAT
• Loss of adipose FAO induces mtDNA stress in BAT
• Loss of adipose FAO does not alter body weight or adiposity at thermoneutrality

SummaryAmbient 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 Pgc1α 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.

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