Abstract
Obesity is associated with increased plasma glycerol levels. The coordinated regulation of glycerol channels in adipose tissue (AQP7) and the liver (AQP9) has been suggested as an important contributor to the pathophysiology of type-2-diabetes mellitus, as it would provide glycerol for hepatic synthesis of glucose and triglycerides. The regulation of AQP7 and AQP9 is influenced by sex. This study investigates the effect of a high-fat diet (HFD) on glycerol metabolism in mice and the influence of sex and GLP-1-receptor agonist treatment. Female and male C57BL/6JRj mice were fed either a control diet or a HFD for 12 or 24 weeks. Liraglutide was administered (1 mg/kg/day) to a subset of female mice. After 12 weeks of HFD, females had gained less weight than males. In adipose tissue, only females demonstrated an increased abundance of AQP7, whereas only males demonstrated a significant increase in glycerol kinase abundance and adipocyte size. 24 weeks of HFD resulted in a more comparable effect on weight gain and adipose tissue in females and males. HFD resulted in marked hepatic steatosis in males only and had no significant effect on the hepatic abundance of AQP9. Liraglutide treatment generally attenuated the effects of HFD on glycerol metabolism. In conclusion, no coordinated upregulation of glycerol channels in adipose tissue and liver was observed in response to HFD. The effect of HFD on glycerol metabolism is sex-specific in mice, and we propose that the increased AQP7 abundance in female adipose tissue could contribute to their less severe response to HFD.
Highlights
Obesity is a key risk factor for developing type-2-diabetes mellitus (T2D)
After 24 weeks of high-fat diet (HFD), the Body weight (BW) was increased by 17 g in both male and female mice compared to controls (p < 0.0001 for both), which corresponds to a 75% increase in females and a 48% increase in males (Figures 2A, B)
We examined the effect of 12 and 24 weeks of 60% HFD feeding in female and male mice on white adipose tissue (WAT) and liver glycerol metabolism
Summary
Obesity is a key risk factor for developing type-2-diabetes mellitus (T2D). The risk for developing T2D is sex-dependent and sex-related differences in triglyceride (TG) metabolism and body fat distribution clearly contribute to this [1]. The molecular mechanisms behind the sex-dependent risk for developing T2D remain largely undetermined. Glycerol is stored as the backbone of TG, predominantly in adipose tissue, and it is released along with fatty acids in response to e.g. fasting and exercise. Obesity is associated with increased plasma glycerol levels [2]. The coordinated upregulation of glycerol channels in white adipose tissue (WAT) and the liver has been suggested as an important contributor to the pathophysiology of T2D, as it would support the increased hepatic
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