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  • Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis.

Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis.

Cell metabolism (2017-09-07)
Judith Simcox, Gisela Geoghegan, John Alan Maschek, Claire L Bensard, Marzia Pasquali, Ren Miao, Sanghoon Lee, Lei Jiang, Ian Huck, Erin E Kershaw, Anthony J Donato, Udayan Apte, Nicola Longo, Jared Rutter, Renate Schreiber, Rudolf Zechner, James Cox, Claudio J Villanueva
ABSTRACT

Cold-induced thermogenesis is an energy-demanding process that protects endotherms against a reduction in ambient temperature. Using non-targeted liquid chromatography-mass spectrometry-based lipidomics, we identified elevated levels of plasma acylcarnitines in response to the cold. We found that the liver undergoes a metabolic switch to provide fuel for brown fat thermogenesis by producing acylcarnitines. Cold stimulates white adipocytes to release free fatty acids that activate the nuclear receptor HNF4α, which is required for acylcarnitine production in the liver and adaptive thermogenesis. Once in circulation, acylcarnitines are transported to brown adipose tissue, while uptake into white adipose tissue and liver is blocked. Finally, a bolus of L-carnitine or palmitoylcarnitine rescues the cold sensitivity seen with aging. Our data highlight an elegant mechanism whereby white adipose tissue provides long-chain fatty acids for hepatic carnitilation to generate plasma acylcarnitines as a fuel source for peripheral tissues in mice.

MATERIALS
Product Number
Brand
Product Description

Avanti
17:1 Lyso PC, Avanti Research - A Croda Brand LM1601, methanol solution
Sigma-Aldrich
IgG, Rabbit, Rabbit IgG Polyclonal Antibody validated for use in ELISA.
Avanti
13:0 Lyso LPC, Avanti Research - A Croda Brand