FAcTs on fire: Exploring thermogenesis.

Abstract

Thermoregulation is a fundamental biological process that allows birds and mammals to maintain a stable internal temperature despite environmental fluctuations, a mechanism shaped by millions of years of evolution. Non-shivering thermogenesis (NST), primarily driven by brown adipose tissue (BAT), plays a central role in thermoregulation by not only helping maintain energy homeostasis but also influencing broader metabolic and physiological processes. Recent research has revealed that BAT thermogenesis is regulated by peripheral hormones and at a central level, with key hypothalamic energy-sensing pathways-such as AMP-activated protein kinase (AMPK) and endoplasmic reticulum (ER) stress-playing critical roles. Beyond its metabolic functions, BAT and NST have emerged as important contributors to tumor biology, offering novel therapeutic strategies for metabolic and oncological diseases. This review explores the intricate mechanisms underpinning NST, including UCP1-dependent thermogenesis and alternative pathways such as creatine cycling, calcium-dependent thermogenesis, and lipid cycling. Emerging evidence further highlights BAT's potential in to modulate tumor metabolism, with pharmacological and genetic approaches showing promise in reshaping the tumor microenvironment. This growing body of knowledge offers exciting prospects for targeting BAT thermogenesis in treating obesity and other metabolic diseases.