Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans.

Abstract

Uncoupling protein-2 and -3 (UCP2 and UCP3) are mitochondrial proteins that show high sequence homology with the brown adipocyte-specific UCP1. UCP1 induces heat production by uncoupling respiration from ATP synthesis. UCP2 is widely expressed in human tissues, whereas UCP3 expression seems restricted to skeletal muscle, an important site of thermogenesis in humans. We have investigated the regulation of UCP2 and UCP3 gene expression in skeletal muscle and adipose tissue from lean and obese humans. UCP2 and -3 mRNA levels were not correlated with body mass index (BMI) in skeletal muscle, but a positive correlation ( r ϭ 0.55, P Ͻ 0.01, n ϭ 22) was found between UCP2 mRNA level in adipose tissue and BMI. The effect of fasting was investigated in eight lean and six obese subjects maintained on a hypocaloric diet (1,045 kJ/d) for 5 d. Calorie restriction induced a similar 2-2.5-fold increase in UCP2 and -3 mRNA levels in lean and obese subjects. To study the effect of insulin on UCP gene expression, six lean and five obese subjects underwent a 3-h euglycemic hyperinsulinemic clamp. Insulin infusion did not modify UCP2 and -3 mRNA levels. In conclusion, the similar induction of gene expression observed during fasting in lean and obese subjects shows that there is no major alteration of UCP2 and -3 gene regulation in adipose tissue and skeletal muscle of obese subjects. The increase in UCP2 and -3 mRNA levels suggests a role for these proteins in the metabolic adaptation to fasting.

Obesity and polymorphisms in genes regulating human adipose tissue

“…[107][108][109][110] Whereas UCP2 is widely expressed, UCP3 is restricted to skeletal muscle and adipose tissue. 111 Visceral fat UCP2 expression is decreased in obese subjects. 112 Otherwise, expression of these genes displays no major dependence on BMI, but both are increased in individuals undergoing fasting, suggesting a role in metabolic adaptation to fasting.…”

“…112 Otherwise, expression of these genes displays no major dependence on BMI, but both are increased in individuals undergoing fasting, suggesting a role in metabolic adaptation to fasting. 111 An SNP at position À866 in the UCP2 promoter that affects mRNA expression in vitro is associated with mRNA levels in visceral fat, obesity, as well as 24-h energy expenditure. 113,114 Additional UCP2 exon SNPs have been associated with basal metabolic rate or 24-h energy expenditure.…”

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

“…In itro and in i o experiments demonstrated that fatty acids or certain retinoids promote UCP2 and\or UCP3 expression in white and brown adipocytes, myocytes and pancreatic islets [171,172,177,206,[229][230][231][232][233][234][235][236][237][238]. Expression of UCP2 and\or UCP3 in skeletal muscles, heart or adipose tissue can be induced by various situations characterized by elevated levels of circulating non-esterified fatty acids, such as starvation in humans or rodents [84,169,239,240], high-fat feeding in rodents [30,177] and genetic or experimental diabetes in rodents [31,241,242]. It is not known whether the very high level of ketone bodies observed in diabetic rats is related to UCP induction [241].…”

UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan

“…10 In obese and lean humans, UCP2 and UCP3 mRNA expression all increase during fasting. 11 A linkage study reported that resting metabolic rate (RMR) and other obesity-related phenotypes are associated with markers at the UCP2/UCP3 locus. 12,13 The following will be investigated in this study: (1) two UCP2 gene polymorphisms, including the G-866A polymorphism in the promoter region, 14 A55V (Ala55Val) polymorphism in exon 4; 15,16 and (2) two UCP3 gene polymorphisms, including the C-55T polymorphism of the promoter [17][18][19] and V102I (Val102Ile) in exon 3.…”