Vagotomy improves brown adipose tissue morphology and reduces steatosis in obese mice

The abolishment of vagal abdominal afferents and efferent inputs through vagotomy has been shown to prevent obesity. However, it is unknown whether such a strategy, performed after obesity installation, may treat or ameliorate obesity and its comorbidities. Here, we aimed to verify the effects of subdiaphragmatic vagotomy on obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) in obese mice that continued to be fed an obesogenic diet after the operation. Obesity was induced in male <i>C57Bl/6</i> mice by ingestion of a high-fat diet (HFD). Afterward, obese (OB) mice were randomly submitted to Sham (OB-Sham group) or subdiaphragmatic vagotomy (OB-Vag group) and continued to be fed a HFD for 8 weeks. Vagotomy led to reductions in body weight, without modifying food intake in OB-Vag mice. While these rodents showed no modifications in subcutaneous fat accumulation, they exhibited higher abdominal adiposity. In contrast, the weight of the interscapular brown adipose tissue (BAT) was lower in OB-Vag mice, with brown adipocytes in its parenchyma showing reduced size and fewer lipid vacuoles, resembling the high-thermogenic adipocyte type. This effect was partially explained by increased gene expressions of <i>Prdm16, Pgc-1α</i>, and <i>Dio2</i>, key factors maintaining BAT identity and function. Furthermore, subdiaphragmatic vagotomy enhanced glucose tolerance, insulin sensitivity, improved serum and hepatic lipids levels, and ameliorated MASLD in OB-Vag mice. Vagotomy performed after obesity induction improved BAT function and insulin sensitivity, which may partly contribute to alleviating MASLD in OB mice that continued to consume an obesogenic diet.