Abstract
The role of uncoupling protein-3 (UCP3) in energy and lipid metabolism was investigated. Male wild-type (WT) and UCP3-null (KO) mice that were housed at thermoneutrality (30 °C) were used as the animal model. In KO mice, the ability of skeletal muscle mitochondria to oxidize fatty acids (but not pyruvate or succinate) was reduced. At whole animal level, adult KO mice presented blunted resting metabolic rates, energy expenditure, food intake, and the use of lipids as metabolic substrates. When WT and KO mice were fed with a standard/low-fat diet for 80 days, since weaning, they showed similar weight gain and body composition. Interestingly, KO mice showed lower fat accumulation in visceral adipose tissue and higher ectopic fat accumulation in liver and skeletal muscle. When fed with a high-fat diet for 80 days, since weaning, KO mice showed enhanced energy efficiency and an increased lipid gain (thus leading to a change in body composition between the two genotypes). We conclude that UCP3 plays a role in energy and lipid homeostasis and in preserving lean tissues by lipotoxicity, in mice that were housed at thermoneutrality.
Highlights
Uncoupling protein-3 (UCP3) is a mitochondrial protein, first discovered in 1997 [1], and prevalently expressed in skeletal muscle (SkM), the heart and brown and white adipose tissues [2].The extent of homology between the UCP1 and uncoupling protein-3 (UCP3) genes led to the proposal that UCP3 might be involved in thermogenic mechanisms, and it does not appear to contribute to cold-induced thermogenesis [3], it has recently proved to be essential in thermogenic responses that are induced by the endotoxin lipopolysaccharide and by the sympathomimetic methamphetamine [4]
The extent of homology between the UCP1 and UCP3 genes led to the proposal that UCP3 might be involved in thermogenic mechanisms, and it does not appear to contribute to cold-induced thermogenesis [3], it has recently proved to be essential in thermogenic responses that are induced by the endotoxin lipopolysaccharide and by the sympathomimetic methamphetamine [4]
The resting metabolic rate (RMR), the resting energy expenditure (REE), and the respiratory quotient (RQ) were detected in 4–5 month old animals, which were acclimated at thermoneutrality for at least two weeks
Summary
Uncoupling protein-3 (UCP3) is a mitochondrial protein, first discovered in 1997 [1], and prevalently expressed in skeletal muscle (SkM), the heart and brown and white adipose tissues [2].The extent of homology between the UCP1 and UCP3 genes led to the proposal that UCP3 might be involved in thermogenic mechanisms, and it does not appear to contribute to cold-induced thermogenesis [3], it has recently proved to be essential in thermogenic responses that are induced by the endotoxin lipopolysaccharide and by the sympathomimetic methamphetamine [4]. Cells 2019, 8, 916 of UCP3 expression are observed under physiological and pathological conditions, in which the fatty acid oxidation rate is elevated [8,9,10]. The expression of UCP3 during heart development is correlated to that of mitochondrial fatty acid oxidation rate markers [11]. The absence of UCP3 negatively influences the ability of SkM mitochondria to oxidize FA [12,13]. In this context, Bouillaud et al [14] suggested that UCP3 could switch cells from carbohydrate to fatty acid metabolic pathways by promoting mitochondrial pyruvate extrusion, which prevents the use of pyruvate as a substrate. Mechanistic information on this possible activity is currently lacking
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