Effects of Recombinant Human Growth Hormone on Multi-Organ Inflammation in Hyperlipidemic mice

Abstract

Recombinant human growth hormone (rhGH) has been developed for the treatment of growth hormone deficiency (GHD) and various short stature disorders. Its physiological and therapeutic effects are well documented. However, rhGH replacement is also associated with dysfunction of lipid and glucose metabolism. Therefore, it is important to understand the exact effect of rhGH treatment on metabolic diseases. Low-density lipoprotein receptor-deficient (LDLR-/-) mice were injected with rhGH, and the effects of GH on the levels of serum cholesterol, triglycerides, and insulin-like growth factor 1 (IGF-1) were analyzed. Also analyzed were the effects of rhGH on inflammatory changes in the liver, adipose tissues and aorta, and the effects of rhGH on hepatic gene expression-related to inflammation and lipid metabolism. Exogenous rhGH treatment increased plasma IGF-1 concentration and led to a decrease in liver and body weight and a reduction in inflammatory changes in visceral adipose tissue (VAT). However, there was no effect on the atherosclerotic process. rhGH treatment reduced macrophage accumulation in adipose tissue, including perivascular and visceral fats. Importantly, rhGH treatment inhibited hepatic fat uptake and eventually reduced hepatic steatosis and inflammation, with attenuated CD36 and interleukin 1 beta (IL-1β) expression. Treatment with rhGH attenuates hepatic steatosis and inflammation without affecting the atherosclerotic process in high-fat diet fed LDLR knockout mice. In the present study, it was considered important to treat with the rhGH dose generally used in clinical therapy and to investigate the exact effects of rhGH treatment on metabolic diseases. The results of this study will be very useful in predicting the effect of GH administration on patients with multiple metabolic syndromes rather than GHD patients.