Targeting the Enteroendocrine System for Treatment of Obesity

Abstract

Mimetics of the anorexigenic gut hormone glucagon-like peptide 1 (GLP-1) were originally developed as insulinotropic anti-diabetic drugs but also evoke significant weight loss, leading to their recent approval as obesity therapeutics. Co-activation of receptors for GLP-1 and other gut hormones which reduce food intake – peptide YY (PYY3–36), cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP) – is now being explored clinically to enhance efficacy. An alternative approach involves pharmacologically stimulating endogenous secretion of these hormones from enteroendocrine cells (EECs) to recapitulate the metabolic consequences of bariatric surgery, where highly elevated postprandial levels of GLP-1 and PYY3–36 are thought to contribute to improved glycaemia and weight loss.