The authors posit that an increase in circulating intestinally derived GIP, as a consequence of overnutrition, acts in the brain to impair hypothalamic leptin action, resulting in increased food intake and body weight gain.
Glucose-dependent insulinotropic polypeptide [also known as gastric inhibitory polypeptide (GIP)] and its receptor (GIPR) may link overnutrition to obesity, insulin resistance, and type 2 diabetes.
In addition, observations in transgenic GIP receptor deficient mice indicate that GIP directly links overnutrition to obesity, therein playing a crucial role in the development of obesity and related metabolic disorders.