Nonalcoholic fatty liver disease become the first metabolism problem in the whole world in recent decades. Low growth hormone (GH) production and/or hepatic GH resistance has also reported to patients with nonalcoholic fatty liver disease (NAFLD). GH and IGF1 replacement can resolve the fatty liver condition in obese rodents and in GH-deficient patients. Those suggest that GH plays a key role in regulating hepatic lipid processing.
However, questions regarding how GH mediates the regulation of hepatic lipid metabolism still remain. Therefore, our laboratory has generated a mouse model with the adipose tissue(AT) -specific GHR knockout (ADGHRKO) by cross Adiponectin cre mice with GHR floxed mice. Combined with high-fat feeding at the same time, the effects of AT-specific GHR gene disruption on the body lipid metabolism was explored comprehensively.
In the current study, we found AT-specific disruption of GHR significantly increased female body weight after 3 mo. but no difference in male. Subcutaneous WAT of male ADGHRKO mice were significantly larger than that of the control littermate whereas several internal organs were significantly smaller such as heart and liver, which may result in the unchanged body weight of male mice. In addition, subcutaneous, gonadal and perinephric WAT of female ADGHRKO mice were increased significantly compared to the control mice.
After a High Fat Diet (60% kcal from fat) treatment for 16 weeks, the ADGHRKO mice were predisposed to diet-induced obesity, but their glucose tolerance and insulin sensitivity were slightly better than the control(LL) littermate mice. ADGHRKO mice also showed the lighter level of severity of the fatty liver which was demonstrated that GHR in adipose tissue may play an important role in regulating adipocyte function and metabolism, the relevant mechanism is yet to be further analysis.