Adipose Y5R mRNA is higher in obese than non-obese humans and is correlated with obesity parameters

Abstract

Neuropeptide Y is mainly expressed in the central nervous system to regulate food intake via its receptors, Y receptors, and in various peripheral tissues including adipose tissue. The objectives of this study were to compare Y5R mRNA and adipocyte parameters consisting of area, width, height, and perimeter either between obese and non-obese subjects or between subcutaneous and visceral fat as well as to compare between NPY, Y1R, Y2R, and Y5R mRNA expressions in subcutaneous and visceral adipose tissues. In subcutaneous and visceral adipose tissues, Y5R was greater in obese than in non-obese humans (both P < 0.05). Y1R mRNA expression was highest followed by Y5R, Y2R, and NPY mRNA expressions, respectively, in subcutaneous and visceral adipose tissues. Visceral Y5R mRNA had positive correlations with body weight, body mass index, waist circumference, hip circumference (R ≍ 0.4), and visceral Y1R mRNA (R = 0.773), but had a negative correlation with the quantitative insulin sensitivity check index (R=-0.421) (all P < 0.05). Subcutaneous and visceral adipocyte parameters were positively correlated with body weight, waist circumference, hip circumference, and waist-to-hip ratio, with greater values of correlation coefficient shown in visceral (R ≍ 0.5-0.8) than in subcutaneous adipocytes (R ≍ 0.4-0.6, all P < 0.05). The parameters of visceral adipocytes had positive correlations with serum NPY levels (R ≍ 0.4, all P < 0.05). Y5R mRNA in visceral adipose tissue is related to increased obesity and reduced insulin sensitivity. The dominant Y receptors in subcutaneous and visceral adipose tissue might be the Y1R and Y5R. Visceral adipocytes show higher correlations with obesity parameters than subcutaneous adipocytes, suggestive of an increased risk of metabolic syndrome in visceral obesity. Y1R and Y5R in visceral adipose tissue might be targets of drug development in prevention or treatment of adiposity. Impact statement Obesity, defined as excess fat accumulation, has been increasingly diagnosed worldwide causing adverse health consequences. The novel findings of this study were that Y5R mRNA expression in both subcutaneous and visceral fat was higher in obese than non-obese subjects. Furthermore, Y5R only in visceral fat, not subcutaneous fat, was positively correlated with visceral Y1R and obesity parameters but it was negatively correlated with the QUICKI. Moreover, we found that Y1R expression was highest followed by Y5R and Y2R, respectively, in both subcutaneous and visceral fat. Our results suggested that Y5R in visceral fat was associated with increased obesity and decreased insulin sensitivity. Y1R and Y5R might be the dominant receptors that mediate the effect of NPY-induced fat accumulation in both subcutaneous and visceral adipose tissues. Y1R and Y5R in visceral adipose tissue might be targets of drug development in prevention or treatment of obesity.

Keywords: Obesity; Y receptor; Y1 receptor; Y5 receptor; adipocyte; neuropeptide Y.

Figure 1.

Mean (±SD) values of NPY, Y1R, Y2R, and Y5R mRNA expressions in subcutaneous and visceral adipose tissue specimens. Panel (a) shows Y5R mRNA expression compared between obese and non-obese subjects in subcutaneous and visceral fat pads. Panel (b) shows Y5R mRNA expression compared between subcutaneous and visceral fat pads in obese and non-obese subjects. Panels (c) and (d) show comparisons among NPY, Y1R, Y2R, and Y5R mRNA expression levels in subcutaneous and visceral adipose tissues, respectively, of obese subjects. Panels (e) and (f) show comparisons among NPY, Y1R, Y2R, and Y5R mRNA expression in subcutaneous and visceral adipose tissues, respectively, of non-obese subjects. *P < 0.05, **P < 0.01, ***P < 0.001, compared between groups.

Figure 2.

H&E staining and graphs showing mean (±SD) data of adipocyte characteristics, including area, width, height, and perimeter. Panels (a) and (b) show morphology of subcutaneous and visceral adipocytes, respectively. Panels (c) and (d) show area, width, height, and perimeter of subcutaneous and visceral adipocytes, respectively, compared between obese and non-obese groups. Panels (e) and (f) show area, width, height, and perimeter of adipocytes in obese and non-obese subjects, respectively, compared between subcutaneous and visceral adipocytes. *P < 0.05, **P < 0.01, ***P < 0.001, compared between groups. (A color version of this figure is available in the online journal.)