Fig. 1
From: Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation
TGF-β signaling in obesity and related diseases. Overnutrition, Western diet, and increased circulating Fatty acids and glucose induces TGF-β expression and hypothalamic inflammation. Elevated TGF-β signaling interacts with other inflammatory pathways, promoting hypothalamic inflammation, which disturbs hunger and satiety signaling and disrupts energy balance. Under normal conditions (left), the TGF-β/Smad3/SPTBN1 pathway maintains lipid and energy homeostasis in the liver, preventing obesity, fibrosis, and cancer by directly suppressing key regulators like CDK4 and Myc. However, excessive energy intake, particularly from a Western diet, triggers Caspase-3-mediated cleavage of SPTBN1, impairing its interaction with SMAD3. This disruption promotes hepatic injury, lipogenesis, and oncogenic transformation, increasing susceptibility to metabolic syndrome and cancer. In adipose tissue (top right), elevated TGF-β levels drive lipogenesis, expansion of white adipose tissue (WAT), whitening of brown adipose tissue (BAT), and suppression of mitochondrial biogenesis. These changes contribute to heightened inflammation, exacerbating metabolic disturbances