Abstract and Introduction
Context: Adiponectin is an adipokine mainly secreted by adipocytes that regulates the metabolism of lipids and glucose. Liver receptor homolog-1 (LRH-1), also named NR5A2, is a nuclear receptor that regulates lipid metabolism and homeostasis.
Objective: The purpose of this study was to compare adiponectin and LRH-1 messenger RNA (mRNA) expression in adipose tissue and LRH-1 expression in skeletal muscle between men and women at baseline and to study the effects of aerobic exercise (AEX) training or weight loss (WL) on their expression.
Methods: This hospital and university setting study included 62 overweight and obese men (n = 23) and women (n = 39) older than 45 years, of whom 41 completed 6 months of WL (n = 21) or AEX (n = 20). Outcomes included abdominal and gluteal adipose tissue and skeletal muscle gene expression.
Results: Adiponectin and LRH-1 mRNA expression in adipose tissue and LRH-1 mRNA expression in skeletal muscle is higher in women than in men (P < .05). Adiponectin mRNA expression in gluteal and abdominal adipose tissue did not change significantly after AEX or WL. LRH-1 mRNA expression increased both in adipose tissue and skeletal muscle after AEX (P < .05) and the change in muscle LRH-1 was different between the groups (P < .05). Adiponectin was positively correlated to LRH-1 in adipose tissue (P < .001). The change in maximal oxygen consumption related to the change in LRH-1 mRNA (r = 0.43; P = .01).
Conclusion: LRH-1, as a nuclear reporter, may activate adiponectin mRNA expression in adipose tissue and increases after AEX.
Adiponectin is an anti-inflammatory, antiatherogenic, and insulin-sensitizing adipokine. Lower plasma concentrations and expression levels are reported in obese individuals and adults with type 2 diabetes. Adiponectin activates insulin receptor substrate-1 (IRS-1)–mediated phophatidylinositol-3 kinase (PI-3K) and glucose uptake in skeletal muscle cells, enhances muscle beta-oxidation via the activation of adenosine 5'-monophosphate (AMP)-kinase, and suppresses hepatic glucose production. It also has antiatherogenic effects, suppressing monocyte adhesion to endothelial cells by reducing nuclear factor-κB signaling and the messenger RNA (mRNA) expression of adhesion molecules in endothelial cells. Adiponectin mRNA expression is higher in lean individuals compared to obese individuals. There are also sex differences in circulating levels of adiponectin in humans. Adiponectin levels are significantly higher in women than men and negatively associated with obesity, fasting glucose, and insulin levels and insulin resistance.[6–9] Adiponectin mRNA expression in epicardial adipose tissue is higher in women than men undergoing some type of heart surgery. A reduced level of high-molecular-weight adiponectin levels is more strongly associated with metabolic syndrome in women than men. In animal models, treatment with testosterone reduces plasma adiponectin, and in adipocyte cell culture, testosterone reduces adiponectin secretion, suggesting androgens may play a role in sex differences of adiponectin.
Liver receptor homolog-1 (LRH-1) is a monomeric orphan nuclear receptor expressed in the liver, pancreas (islets, β-cells), intestine, ovary, adrenal glands, preadipocytes, adipose tissue, and skeletal muscle.[13,14] It is mostly recognized for its role in early development, cholesterol homeostasis, and cancer. LRH-1 has emerged as an upstream regulator of the glucokinase-carbohydrate response element binding protein axis. LRH-1 controls the first step of hepatic glucose uptake through direct transcriptional regulation of the glucokinase gene. Thus, LRH-1 may play a role in insulin sensitivity.
The LRH response element is located downstream of the peroxisome-proliferator response element in the human adiponectin promoter and in mature adipocytes enhances the transcription of adiponectin. It is interesting to speculate that increasing LRH-1 would lead to the increased transcription of adiponectin, which would improve insulin sensitivity. However, the role of LRH-1 and insulin sensitivity has not been examined. Further, there are no studies that have examined the effect of exercise and diet on LRH-1 response. In contrast, there are several studies that use aerobic exercise training (AEX), weight loss (WL), or both that have shown adiponectin mRNA expression increases[2,15–17] or does not change.[18,19] The reasons for the discrepancies among studies is unclear; however, participant characteristics such as age may play a role.
The purpose of this study was to compare adipose tissue adiponectin mRNA expression and adipose and skeletal muscle LRH-1 mRNA expression between older overweight and obese men and women before the interventions and study the effects of 6-month WL and AEX interventions on their expression. We hypothesized that adiponectin and LRH-1 mRNA expression would be related to each other and to insulin sensitivity and that 6-month WL and AEX interventions would increase adiponectin and LRH-1 expression in adipose tissue and skeletal muscle.
J Endo Soc. 2022;6(8) © 2022 Endocrine Society