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Abstract
Background:A membrane-penetrating cation, dodecyltriphenylphosphonium (C12 TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12 TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans.Methods:We investigated the metabolic effects of C12 TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry.Results:In mice, C12 TPP (50 μmol per (day[DOT]kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12 TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12 TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12 TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12 TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12 TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12 TPP-treated mice was due to reduced food intake. C12 TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12 TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice.Conclusions:C12 TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation.