Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean

Abstract

Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial transporter superfamily that is expressed predominantly in skeletal muscle. However, its close relative UCP-1 is expressed exclusively in brown adipose tissue, a tissue whose main function is fat combustion and thermogenesis. Studies on the expression of UCP-3 in animals and humans in different physiological situations support a role for UCP-3 in energy balance and lipid metabolism. However, direct evidence for these roles is lacking. Here we describe the creation of transgenic mice that overexpress human UCP-3 in skeletal muscle. These mice are hyperphagic but weigh less than their wild-type littermates. Magnetic resonance imaging shows a striking reduction in adipose tissue mass. The mice also exhibit lower fasting plasma glucose and insulin levels and an increased glucose clearance rate. This provides evidence that skeletal muscle UCP-3 has the potential to influence metabolic rate and glucose homeostasis in the whole animal.

Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans

“…That this increase in energy expenditure is directly related to the tumour effect is evidenced by the fact that removal of tumour ensures prompt restoration of normal metabolism (Luketich et al, 1990). UCP-3, when overexpressed in the skeletal muscle of transgenic mice results in a lean phenotype, with increased energy expenditure compared to controls (Clapham et al, 2000). Over expression of UCP-3 in the skeletal muscle of human cancer patients might contribute to increase energy expenditure and thus to weight loss.…”

“…Both have uncoupling activity in vitro and may mediate the increased energy expenditure implicated in energy balance. Transgenic mice over-expressing UCP-3 in muscle are lean despite exhibiting hyperphagia; oxygen consumption in the transgenic animals was increased by 91% indicating an increase in metabolic rate (Clapham et al, 2000). The exact roles of the various UCP isoforms in vivo are still debated and are reviewed elsewhere (Ricquier and Bouillaud, 2000).…”

Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

“…The uncoupling protein 3 (UCP3) is a muscle-specific isoform, which seems to be involved in fat oxidation and regulation of body fat content. 4 It has been demonstrated that fatty acids either in their unesterified form or as part of dietary fats are able to influence a variety of parameters related with energy homeostasis, such as body fat mass, lipid metabolism, thermogenesis, and food intake. For example, consumption of fish oil, whose major lipid components are the polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acid with a chain length of 20 and 22 carbon atoms, respectively, decreased total body fat in Wistar rats.…”

Uncoupling protein-2: evidence for its function as a metabolic regulator

“…Although none of the UCP ±/± mice (1, 2 or 3) is obese [10, 48, 111, 140, 141] it remains to be determined how UCP2 interacts with other potential energy monitoring molecules to participate in weight homeostasis. Of interest are data showing that mice with skeletal muscle-specific induction of UCP3 have decreased body weight despite normal [142] or increased food intake [143]. The metabolic rate is increased, as is insulin sensitivity and glucose uptake, whereas adipose tissue mass is reduced by about 50 % [143].…”

“…Of interest are data showing that mice with skeletal muscle-specific induction of UCP3 have decreased body weight despite normal [142] or increased food intake [143]. The metabolic rate is increased, as is insulin sensitivity and glucose uptake, whereas adipose tissue mass is reduced by about 50 % [143].…”