bioRxiv Biochemistry
bioRxiv Biochemistry
5 years ago

Global analysis of plasma lipids identifies liver-derived acyl-carnitines as a fuel source for brown fat thermogenesis

Geoghegan, Cox, Lee, U., R., S., Huck, A., G., Maschek, Longo, Rutter, Donato, Apte, C. J., I., Miao, Villanueva, N., M., Jiang, Simcox, L., J., J. A., Pasquali
Cold induced thermogenesis is an energy demanding process that protects endotherms against a reduction in ambient temperature. Using non-targeted LC-MS based lipidomics, we identified plasma acylcarnitines as the most significantly changed lipid class in response to the cold. Here we show that acylcarnitines provide fuel for brown fat thermogenesis. In response to the cold, FFAs released from adipocytes activate the nuclear receptor HNF4 to stimulate the expression of genes involved in acylcarnitine metabolism in the liver. Conditional deletion of HNF4 in hepatocytes blocks the cold-induced changes in hepatic gene expression, lowering circulating long chain acylcarnitine (LCAC) levels, and impairing their ability to adapt to the cold. Finally, a bolus of L-carnitine or palmitoylcarnitine rescues the cold sensitivity seen with aging. Our data highlights an elegant mechanism whereby white adipose tissue provides FFAs for hepatic carnitilation to generate plasma LCAC as a fuel source for BAT thermogenesis.

Publisher URL: http://biorxiv.org/cgi/content/short/132241v1

DOI: 10.1101/132241

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