Background: Brown adipose tissue (BAT) is well established as a regulator of thermogenesis and energy expenditure. Recently, BAT has emerged as an endocrine organ that communicates with other metabolic tissues through secreted factors. However, whether BAT directly regulates pancreatic β-cell function remains unclear. We investigated how loss of uncoupling protein 1 (UCP1) and dietary conditions affect whole-body glucose homeostasis, islet function and BAT–islet communication.
Methods: Wild-type (WT) and UCP1-knockout (UCP1KO) mice were maintained on a chow diet or high-fat diet (HFD) for 8 weeks. Body weight and blood glucose were monitored weekly, and GTT were performed at week 4. At endpoint, pancreatic islets were isolated for ex vivo glucose-stimulated insulin secretion (GSIS) to assess β-cell function. For co-culture experiments, islets isolated from chow- or HFD-fed WT and UCP1KO mice were incubated for 48 hours with conditioned medium (CM) collected from mature adipocytes derived from BAT or inguinal white adipose tissue of chow- or HFD-fed WT and UCP1KO mice. GSIS was assessed after CM treatment.
Results: UCP1KO mice were resistant to HFD-induced weight gain but exhibited higher blood glucose and impaired glucose tolerance under both chow and HFD conditions. At endpoint, islets isolated from HFD-fed UCP1KO mice exhibited enhanced insulin secretion compared with WT islets, whereas no genotype-dependent difference was detected under chow conditions. CM from WT BAT suppressed GSIS in WT islets under both chow and HFD conditions.
Conclusion: UCP1 deficiency dissociates resistance to HFD-induced weight gain from the maintenance of glucose homeostasis. BAT-derived factors exert a direct inhibitory effect on pancreatic islets across dietary conditions and may act as a physiological brake that protects β-cells from excessive stimulation. These findings identify BAT–islet communication as an important regulator of insulin secretion and metabolic homeostasis during obesity.