Latest Advances in Obesity Treatment by Regulating Adipocyte Thermogenesis

Obesity is driven by chronic energy imbalance and is associated with multiple metabolic diseases. As adipocyte thermogenesis contributes to energy expenditure, it is being actively investigated as a possible target for obesity treatment. This review summarizes recent progress in the molecular regulation of adipocyte thermogenesis, focusing mainly on preclinical mechanistic evidence from cellular and animal studies, while discussing clinical and human data only where available. We review emerging regulators within the cAMP pathway, the PRDM16-PPARγ axis, and mitochondrial quality control and metabolism, together with other pathways that modulate brown and beige adipocyte function. We also discuss their metabolic effects in experimental obesity settings. Nevertheless, the therapeutic relevance of these findings remains uncertain because much of the evidence is still preclinical, and because translation is complicated by species differences, adipose depot heterogeneity, and the limited number of validated human studies. This review therefore offers an updated synthesis of recent mechanistic advances while emphasizing the key challenges that must be addressed before these insights can be reliably translated into obesity therapies.