Role of the Th2-like Immune Response in Obesity: IL-4 as a Metabolic Regulator and IL-13 as an Effector of Muscle Energy Metabolism

Abstract

The Th2 immune response, associated with allergic diseases and helminth infections, has emerged as a significant modulator of metabolic processes in adipose and liver tissues. Th2 cytokines, such as IL-4, IL-5, and IL-13, regulate energy metabolism, insulin resistance, and obesity-related issues. IL-4 and IL-13 play significant roles, while IL-5 mainly recruits eosinophils in visceral fat. IL-4 influences lipid metabolism via STAT6, promoting adipogenesis, lipolysis, and reducing leptin levels, thereby improving insulin resistance or inducing white adipose browning in the absence of leptin. IL-13 affects glucose metabolism by lowering gluconeogenesis and enhancing glucose control and increases energy expenditure in muscles during exercise via STAT3. Emerging therapies include recombinant cytokines, exosomes, and monoclonal antibodies targeting IL-4/IL-13 or IL-5, which are mostly approved for the treatment of allergic diseases. Their use in metabolic disorders is largely unexplored. Overall, Th2 cytokines are promising targets for obesity and metabolic diseases but require dedicated trials to assess benefits and risks.