Gene Expression of Adiponectin Receptors in Human Visceral and Subcutaneous Adipose Tissue Is Related to Insulin Resistance and Metabolic Parameters and Is Altered in Response to Physical Training

Abstract

OBJECTIVE -Adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively) mediate the effects of adiponectin on glucose and lipid metabolism in vivo. We examined whether AdipoR1 and/or AdipoR2 mRNA expression in human adipose tissue is fat-depot specific. We also studied whether their expression in visceral and subcutaneous fat depots is associated with metabolic parameters and whether their expression is regulated by intensive physical exercise.RESEARCH DESIGN AND METHODS -We determined metabolic parameters and assessed AdipoR1 and AdipoR2 mRNA expression using quantitative real-time PCR in adipose tissue in an observational study of 153 subjects and an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes) before and after intensive physical training for 4 weeks.RESULTS -AdipoR1 and AdipoR2 mRNA expression is not significantly different between omental and subcutaneous fat, but their expression is several-fold lower in adipose tissue than in muscle. AdipoR2 mRNA expression in visceral fat is highly correlated with its expression in subcutaneous fat. AdipoR2 mRNA expression in both visceral and subcutaneous fat is positively associated with circulating adiponectin and HDL levels but negatively associated with obesity as well as parameters of insulin resistance, glycemia, and other lipid levels before and after adjustment for fat mass. Physical training for 4 weeks resulted in increased AdipoR1 and AdipoR2 mRNA expression in subcutaneous fat.CONCLUSIONS -AdipoR2 mRNA expression in fat is negatively associated with insulin resistance and metabolic parameters independently of obesity and may mediate the improvement of insulin resistance in response to exercise. Diabetes Care 30:3110-3115, 2007A diponectin is an adipose tissuesecreted cytokine that acts as a key modulator of insulin sensitivity (1,2) and glucose and lipid metabolism (3) and has pronounced antiatherosclerotic effects (4,5). The beneficial effects of this highly abundant 244 -amino acid protein hormone (circulating at ϳ10 g/ml concentration in human serum and accounting for ϳ0.01% of total plasma protein) are predominantly mediated by two cell membrane receptors, adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) (6).AdipoR1 is a high-affinity receptor for globular adiponectin, and studies in mice have shown that it is ubiquitously expressed (6 -10) but most abundantly in skeletal muscle. AdipoR2 is predominantly expressed in liver and has intermediate affinity for both full-length and globular adiponectin (6,8). Simultaneous disruption of both AdipoR1 and AdipoR2 abolished adiponectin binding and actions, resulting in increased tissue triglyceride content, inflammation, and oxidative stress, leading to insulin resistance and glucose intolerance in mice (9). Elevated expression of AdipoR1 and AdipoR2 has been associated with decreased plasma insulin levels in mice in either physiological (i.e., fasting) or pathological conditions (11). We have previously reported that prolonged e...

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

“…29 Euglycaemic-hyperinsulinaemic clamp studies showed that ADIPOR2, but not ADIPOR1 mRNA levels in visceral and subcutaneous AT were correlated with whole-body glucose uptake. 41 In skeletal muscle, the data are less consistent. In non-diabetic Mexicans, lower ADIPOR1/2 mRNA levels in skeletal muscle have been observed in subjects with a family history of type 2 diabetes than in those with no family history of the disease, 42 but ADIPOR1/2 mRNA levels were similar in skeletal muscle of patients with type 2 diabetes and lean controls.…”

Influência do estado nutricional e do VO2max nos níveis de adiponectina em homens acima de 35 anos

“…Four weeks of intensive physical training resulted in increases in skeletal muscle AdipoR1/R2 mRNA expression. The same intervention led to increases in AdipoR1 and AdipoR2 mRNA expression in subcutaneous fat and it was significantly and positively correlated with the increases of AdipoR2 in skeletal muscle 13 .…”

“…Although controversial, few studies [10][11][12] have suggested a direct relationship between the levels of adiponectin and physical activity and, as pointed out by Blüher et al 13 , physical training appears to increase the number of adiponectin receptors in subcutaneous fat. However, only a few studies have associated adiponectin plasma levels with objective measures of cardiorespiratory fitness.…”

Increased circulating adiponectin levels and decreased leptin/soluble leptin receptor ratio throughout puberty in female ballet dancers: association with body composition and the delay in puberty

“…Adiponectin is negatively correlated with body weight and central adiposity, and its receptors are present in human bone-forming cells, suggesting that adiponectin may link bone and fat metabolism (14). Richards et al (41) found that in nondiabetic women, the increase in adiponectin is associated with a decrease in BMD.…”

“…This peptide acts as a satiety signal that stimulates energy expenditure regulating body weight (11), with these actions being modulated by a soluble receptor (12). Physical exercise increases adiponectin levels (13) and the expression of its receptors in muscle (14), and this adipokine may have beneficial effects on the cardiovascular system (15,16).…”