The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects

Abstract

The uncoupling proteins 2 and 3 (UCP2 and UCP3) are probable candidates for underlieing the variability in human energy metabolism. The uncoupling protein genes encode for mitochondrial protein carriers, which uncouple mitochondrial respiration from ATP production and thus stimulates heat production [1]. The UCP2 is ubiquitously expressed in different tissues, whereas UCP3 is mainly expressed in skeletal muscle [2,3]. Furthermore, UCP3 is expressed in a long (UCP3L) and a short (UCP3S) isoform, the latter lacking part of exon 6 and exon 7, probably resulting in a truncated protein. Genetic studies have indicated that polymorphisms in the UCP2 or UCP3 gene or both are associated with altered metabolic rate [4,5]. Recently, we showed that the expression Diabetologia (2000) Abstract Aims/hypothesis. The aim of this study was to examine the effect of weight loss on UCP2/UCP3 mRNA expression and UCP3 protein content in subjects with Type II (non-insulin-dependent) diabetes mellitus.Methods. We studied seven Type II diabetic subjects who followed a 10-week very low calorie diet. Expression of skeletal muscle UCP2 and UCP3 mRNA was measured using RT-competitive PCR and UCP3 protein content by western blotting, before and after the diet. Total and plasma fatty acid oxidation was measured using infusion of 13 C labelled palmitate. Results. Body weight decreased from 105.5 8.2 kg to 91.6 7.2 kg (p < 0.001), after 10 weeks of diet intervention. Expression of UCP2 and UCP3 mRNA were significantly reduced after 10 weeks of diet (p < 0.05) but UCP3 protein contents were not significantly altered. Notably, the change in UCP3L mRNA expression and UCP3 protein content after the very low calorie diet were negatively associated with changes in body weight (r = ± 0.97, p = 0.006 and r = ± 0.83, p = 0.043, respectively) and BMI (r = ± 0.99, p = 0.0007 and r = ± 0.9, p = 0.016, respectively). Furthermore, changes in UCP3L mRNA expression and UCP3 protein content induced by the diet were positively correlated with changes in cytosolic fatty acid-binding protein content (r = 0.93, p = 0.023 and r = 0.84, p = 0.039, respectively). No correlation between diet-induced changes in UCP3 protein and resting energy expenditure or plasma non-esterified fatty acid concentrations were found. Conclusion/interpretation. The negative correlation between the change in UCP3 protein content after weight loss and the change in BMI, suggests that the decrease in UCP3 during weight loss could prevent further weight loss. The finding that the change in UCP3 protein content correlates with the change in skeletal muscle fatty acid-binding protein content, suggests a role for UCPs in the handling of lipids as a fuel. [Diabetologia (2000)

Capsiate administration results in an uncoupling protein-3 downregulation, an enhanced muscle oxidative capacity and a decreased abdominal fat content in vivo

“…The reliability of this quantitative method has been previously demonstrated in rats. 20 In humans, it has been reported that a significant muscle reduction of UCP3 mRNA expression was associated with a weight loss 21,22 further illustrating the potential role of UCP3 in the control of weight gain. Interestingly, the capsiateadministrated rats showed a lower weight gain coupled to a decreased abdominal fat content although they were hyperphagic as compared to control animals.…”

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene (PGC1A) during weight loss is related to insulin sensitivity but not to energy expenditure

“…We previously demonstrated that, when body weight is stable, UCP3 expression in the skeletal muscle of obese participants is not significantly related to the basal metabolic rate [22]. However, the decreased UCP3 expression repeatedly reported in post-obese patients [23][24][25] suggests that, during the weight loss process, downregulation of UCP3 could lead to energy conservation, thus limiting the extent of weight loss. Therefore, UCP3 is a potential determinant of energy expenditure during weight loss.…”

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

“…However, contrary findings are also reported. When weight loss is induced by dietary restriction rather than fasting, UCP2 mRNA in vastus lateralis muscle increases slightly [96,101]. Of interest, UCP2 expression in the vastus lateralis muscle of tetraplegic patients is increased by nearly fourfold compared with able-bodied subjects.…”