UCP2, UCP3 and leptin gene expression: modulation by food restriction and leptin

Abstract

To determine the effects of food restriction and leptin administration on several transcripts involved in energy homeostasis, we examined leptin, uncoupling proteins (UCP) 1, 2 and 3, lipoprotein lipase (LPL), 3 -adrenergic receptors ( 3 AR) and hormone-sensitive lipase (HSL) mRNA levels in brown adipose tissue (BAT) and epididymal (EWAT) and perirenal (PWAT) white adipose tissue in three groups of rats. The groups were administered leptin for 1 week, or had food restricted to the amount of food consumed by the leptin-treated animals, or had free access to food. Leptin administration increased serum leptin concentrations 50-fold and decreased food consumption by 43%, whereas serum insulin and corticosterone concentrations were unchanged. Leptin increased LPL mRNA by 80%, UCP1 mRNA twofold, and UCP3 mRNA levels by 62% in BAT, and increased UCP2 mRNA levels twofold in EWAT. In contrast, UCP2 mRNA levels were unchanged in PWAT and BAT. In WAT from food-restricted rats, leptin gene expression was diminished by 40% compared with those fed ad libitum. With leptin administration, there was a further 50% decrease in leptin expression. LPL mRNA levels were decreased by food restriction but not by leptin in WAT, whereas 3 AR and HSL mRNA levels were unchanged with either food restriction or leptin treatment. The present study indicates that leptin increases the gene expression of UCP2 in EWAT and that of UCP1, UCP3 and LPL in BAT, whereas reduced food consumption but not leptin, decreases LPL expression in WAT. In addition, with leptin administration there is a decrease in leptin gene expression in WAT, independent of food intake and serum insulin and corticosterone concentrations.

Changes in UCP mRNA expression levels in brown adipose tissue and skeletal muscle after feeding a high-energy diet and relationships with leptin, glucose and PPARγ

“…Thus, in this dietary trial, high-energy diet intake significantly increased iBAT UCP1 and UCP3 mRNA levels as previously reported [11,30], which suggests that mechanisms controlling UCP1 and UCP3 expression may be similar. Also, several studies carried out to clarify UCP regulation under different experimental circumstances revealed that ␤ 3 -adrenergic agonists [10,31], leptin infusion [32,33], thyroid hormone administration [4,11] and cold exposure [11,32] induced a significant increase in UCP1 and UCP3 mRNA levels. The results of these studies suggested that the gene expression of both UCPs were similarly modified by those factors that occur after feeding a high-energy diet.…”

Nutritional and hormonal regulation of uncoupling protein 2

“…In the inguinal fat pad of ob/ob mice, treatment with leptin induces the expression of Ucp2 and other genes involved in lipid metabolism, including SREBPs and PPARs (84). In rat studies, subcutaneous administration of leptin was found to induce up-regulation of Ucp2 in epididymal fat pads (85). Adenovirus-mediated overexpression of leptin can also induce up-regulation of Ucp2 in pancreatic beta-cells and subcutaneous white adipose tissues (86).…”

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

“…In addition, both fasting plasma leptin [72] and insulin concentrations [72,73] are negatively correlated with WAT UCP2 mRNA expression, although this finding is not supported by other data [65]. In wellcontrolled studies in rats, where leptin effects can be separated from those of weight loss, both intracerebroventricular [42] and peripherally-administered leptin [74] increase UCP2 expression in WAT. This effect is likely to be mediated by the sympathetic nervous system because leptin added directly to human adipocyte explants does not alter UCP2 expression [75].…”

“…In addition to the complications arising from the dominance of UCP1 in adaptive thermogenesis, there is considerable variability in reported tissue UCP2 mRNA. Since leptin appears to upregulate UCP2 [42,74], it might be hypothesized that leptin-deficient or leptin-resistant animals would have attenuated UCP2 expression. However, not only is leptin not essential for UCP2 expression, it seems that even similar causes of obesity have disparate effects on UCP2 expression [9,16,89,144].…”