Impact of Impaired Hepatic Metabolism on Obesity Related Hypertension Development

Obesity is the primary co-morbidity for cardiovascular disease risk factors, and while it is known that obesity-induced increases in sympathetic-nervous system activation results in systemic hypertension, the mechanisms that generate increased sympathetic signaling are not completely known. Recent work has shown that decreased liver ATP, seen in obese conditions, was associated with reduced hepatocyte membrane potential, and acute hepatocyte membrane depolarization resulted in reduced vagus nerve afferent firing rate. As such, we sought to investigate how altered peripheral vagal afferent signals from the liver impact obesity-induced hypertension development following a chronic high-fat diet. Our lab has previously observed that impaired hepatocyte mitochondrial energy metabolism in (LPGC1a+/-; liver-specific, PGC1a heterozygous) mice results in increased short-term high-fat diet-induced weight gain. PGC1a is an important regulator of mitochondrial biogenesis and has been observed to be reduced in obese individuals. LPGC1a male mice have increases cFos+ cells in the NTS, suggesting maladaptive sensory signaling. In addition, LPGC1a male mice have increased blood pressure compared to WT littermates. Interestingly, female LPGC1a mice have reduced blood pressure compared to WT littermates. Together these results suggest that a reduced liver energy state, driven by reductions in PGC1a, modulates blood pressure in a sex-specific manner on a chronic high-fat diet. This work was partially supported by NIH grants K01DK112967 (EMM) and Kansas INBRE P20 GM103418 (EMM), T32-DK128770 (MEP). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.