GH Fragment AOD9604 Shows Promise for Obesity, Avoiding GH Side Effects

Obesity is a global health crisis characterized by excessive body fat accumulation, leading to numerous metabolic complications. While human growth hormone (GH) is known to influence lipid metabolism and reduce fat mass, its broader effects on glucose homeostasis and potential side effects limit its therapeutic use for obesity. This study aimed to investigate the chronic effects of GH and its specific lipolytic fragment, AOD9604, on lipid metabolism in obese and genetically modified mice, seeking a safer alternative for fat reduction.

Chronic treatment with AOD9604 significantly reduced body weight and fat mass in obese mice without affecting glucose levels or insulin sensitivity. AOD9604 treatment led to a 15% reduction in total body weight and a 28% decrease in fat mass in obese mice compared to saline controls (p<0.001), while GH caused a 12% weight reduction but also increased insulin resistance. Specifically, AOD9604 increased lipolysis (fat breakdown) by 2.5-fold in adipose tissue and enhanced fat oxidation, as evidenced by elevated plasma free fatty acids and glycerol. Importantly, the beneficial effects of AOD9604 on fat mass reduction and lipolysis were maintained in beta(3)-AR knock-out mice, indicating that its mechanism of action is independent of the beta(3)-adrenergic receptor pathway. In contrast, GH treatment, while reducing fat, also significantly increased plasma insulin levels by 30% in obese mice (p<0.05), suggesting potential diabetogenic effects.