Expression of mRNAs encoding uncoupling proteins in human skeletal muscle: effects of obesity and diabetes.

Bao, Shichun; Kennedy, Allan Laurence; Wojciechowski, Barbara; Wallace, Penny; Ganaway, E.; Garvey, W. Timothy

doi:10.2337/diabetes.47.12.1935

Cited by 93 publications

(76 citation statements)

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“…The results of this study are in agreement with the previously observed relationship between plasma leptin levels and UCP3 mRNA levels in skeletal muscle. Note that we did not find a relationship between UCP3 mRNA expression and body fat percentage in this study; however, Bao et al (2) have shown a positive correlation of skeletal muscle UCP3 mRNA with body fat percentage and BMI in nondiabetic individuals. A potential explanation for the absence of this relationship within the current data is that this sample is relatively lean.…”

Section: Discussioncontrasting

confidence: 51%

Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults

Calsbeek

Thompson²,

Dahl³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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This cross-sectional investigation sought to determine the relationship between selected metabolic, endocrine, and anthropometric factors and skeletal muscle UCP3 mRNA in healthy adult humans. Twenty-four healthy adults (13 male and 11 female) across a range of aerobic capacity, age, and body composition were studied. Muscle biopsies were obtained from the vastus lateralis, from which UCP3 mRNA was quantified by Northern blot, and fiber type was determined by use of the myosin ATPase staining procedure. In addition, resting energy expenditure and maximum rate of oxygen consumption were determined by indirect calorimetry, body composition was determined by dual-energy X-ray absorptiometry, and fasting plasma leptin and insulin were determined by ELISA. UCP3 mRNA was correlated positively with the percent type I fibers (r ϭ 0.842, P Ͻ 0.001), plasma leptin (r ϭ 0.454, P ϭ 0.026), and plasma insulin (r ϭ 0.615, P Ͻ 0.001) and inversely to age (r ϭ Ϫ0.411, P ϭ 0.046). Stepwise multiple regression analysis determined that percent type I muscle fibers was the best predictor of vastus lateralis UCP3 mRNA, and no other variable entered the equation (model r 2 ϭ 0.66). This study suggests that of the variables measured, UCP3 mRNA is primarily related to skeletal muscle fiber type in healthy adults. The factors that contribute to fiber-specific differences in UCP3 mRNA expression will need to be examined in future studies. uncoupling proteins; leptin; metabolic rate THE FACTOR(S) THAT CONTRIBUTE to the interindividual variability in resting metabolic rate have been the subject of intense research interest (38,44,54). The recent cloning of novel uncoupling protein isoforms (UCP2 and UCP3) has stimulated interest in potential molecular mediators of the variability in metabolic rate and susceptibility to obesity (8,13,15). The canonical UCP isoform (UCP1) is well accepted to act as an uncoupler of electron transport and oxidative phosphorylation in brown adipose tissue (BAT), resulting in the regulated production of heat (11,25). In contrast, there is considerable debate about whether the novel UCPs are truly uncouplers in vivo, and the specific physiological role of UCP2 and UCP3 in skeletal muscle remains to be elucidated (33). There is evidence indicating that UCP2 and UCP3 function similarly to UCP1 in dissipating the proton gradient of the inner mitochondrial membrane during oxidative respiration (8,13,15,17). It is intuitive then to investigate the relationship between the expression of these novel proteins and other variables known to be associated with metabolism.Studies aimed at understanding the regulation of UCP3 gene expression have demonstrated tissue-specific responses to perturbations designed or "hypothesized" to alter UCP3 gene regulation. The expression and regulation of UCP3 in skeletal muscle are of considerable interest because of the large mass of this organ and its well-documented contribution to both basal metabolism (40) and basal proton leak (39). UCP2 is speculated to function similarly to UCP3; ho...

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Section: Discussioncontrasting

confidence: 51%

Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults

Calsbeek

Thompson²,

Dahl³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…Suggested alternative functions include the regulation of lipid (especially FFA) metabolism, as various situations that raise circulating levels of FFA increase both UCP-2 and -3 expression in white fat and skeletal muscle (Boss et al, 2000). These conditions include fasting, high-fat feeding and intralipid infusion in rodents (Boss et al, 1997a;Fleury et al, 1997;Matsuda et al, 1997;Weigle et al, 1998) and obesity, type-2 diabetes and intralipid infusion in man (Millet et al, 1997;Bao et al, 1999;Khalfallah et al, 2000;Nisoli et al, 2000). Moreover, in vitro, FFA up-regulate UCP-2 in pre-adipocytes and hepatocytes, and UCP-3 in muscle cells (Samec et al, 1998b;Cortez-Pinto et al, 1999;Reilly and Thompson, 2000).…”

mentioning

confidence: 99%

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

et al. 2002

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The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (710%, P=0.03) and fat mass (720%, P50.01) accompanied by a marked decrease in plasma leptin (759%, P50.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P50.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P50.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P50.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.

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“…Type II diabetes mellitus is associated with hypertriglyceridaemia, hypercholesterolaemia and increased NEFA in plasma. As noted above, UCP2 expression in skeletal muscle of human diabetic patients is increased [97,100]. In fa/fa rat muscle, no difference [144] or a decrease in expression is reported [89].…”

Section: Relation Of Ucp2 With Metabolic Diseasesmentioning

confidence: 70%

“…In contrast, patients with Type II (non-insulin-dependent) diabetes mellitus show increased UCP2 mRNA in the vastus lateralis muscle, a primarily oxidative-type tissue [97,100]. While fasting in both lean and non-diabetic obese subjects results in an increased UCP2 gene expression [17,100] no change is observed in diabetic patients [100].…”

Section: Fuel Metabolismmentioning

confidence: 99%

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

2002

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Uncoupling protein-2 (UCP2) was discovered in 1997 but a definitive understanding of its functions has so far eluded investigators. Potential roles include regulating fat metabolism directly and indirectly via effects on insulin secretion. Also, UCP2 could also negatively modulate the production of reactive oxygen species (ROS). Although evidence in support of these functions is correlational, research on UCP2 mechanisms of action has recently been published. Studies of polymorphisms in the uncoupling protein-2 gene have not been included in detail here but are reviewed elsewhere [1,2]. For an in depth discussion of the uncoupling protein family of proteins, readers are referred to recent reviews [1, 3]. Chemical properties of uncoupling proteinsMitochondrial metabolism generates more than 90 % of the ATP required by organisms for routine cellular processes. The efficiency of ATP formation could be altered by demand, by drugs or by pathological processes. Uncoupling agents dissociate fuel oxidation in the electron transport chain of mitochondria from phosphorylation of substrate, namely ADP. Normally, glucose-derived NADH and FADH 2 stimulate Diabetologia (2002) AbstractUncoupling protein-2, discovered in 1997, belongs to a family of inner mitochondrial membrane proteins that, in general, function as carriers. The function(s) of uncoupling protein-2 have not yet been definitively described. However, mounting evidence suggests that uncoupling protein-2 could act in multiple tissues as a regulator of lipid metabolism. A role as a modulator of reactive oxygen species as a defence against infection is also postulated. In this review, a brief overview of the general and specific properties of uncoupling protein-2 is given and evidence for metabolic and immune regulatory functions is summarized.Uncoupling protein-2 could have particular importance in the regulation of lipid metabolism in adipose tissue and skeletal muscle. In addition, its ability to inhibit insulin secretion could also promote fat utilization over storage. Inhibition by uncoupling protein-2 of reactive oxygen species formation in macrophages and other tissues could have implications for regulation of immune function. The possibility of functions of uncoupling protein-2 in other tissues such as the brain are beginning to emerge. [Diabetologia (2002) 45: 174±187]

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Expression of mRNAs encoding uncoupling proteins in human skeletal muscle: effects of obesity and diabetes.

Cited by 93 publications

References 0 publications

Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults

Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

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

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