Stress-induced FGF21 and GDF15 in obesity and obesity resistance

Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are established as stress-responsive cytokines that can modulate energy balance by increasing energy expenditure or suppressing food intake, respectively. Despite their pharmacologically induced beneficial effects on obesity and comorbidities, circulating levels of both cytokines are elevated during obesity and related metabolic complications. On the other hand, endocrine crosstalk via FGF21 and GDF15 was also reported to play a crucial role in genetically modified mouse models of mitochondrial perturbations leading to diet-induced obesity (DIO) resistance. This review aims to dissect the complexities of endogenous FGF21 and GDF15 action in obesity versus DIO resistance for the regulation of energy balance in metabolic health and disease.