Adipose and Skeletal Muscle Expression of Adiponectin and Liver Receptor Homolog-1 With Weight Loss and Aerobic Exercise

Alice S. Ryan; Guoyan Li


J Endo Soc. 2022;6(8) 

In This Article

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.[1] Lower plasma concentrations and expression levels are reported in obese individuals and adults with type 2 diabetes.[2] 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.[3] 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.[4] Adiponectin mRNA expression is higher in lean individuals compared to obese individuals.[5] There are also sex differences in circulating levels of adiponectin in humans. Adiponectin levels are significantly higher in women than men[6] 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.[10] A reduced level of high-molecular-weight adiponectin levels is more strongly associated with metabolic syndrome in women than men.[11] In animal models, treatment with testosterone reduces plasma adiponectin, and in adipocyte cell culture, testosterone reduces adiponectin secretion,[12] 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.[3] 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.