Ovarian Tissue Transplants Reprogram Hepatic Lipid Metabolism in Aged Mice, Reducing β-Oxidation Proteins and Triglycerides

Aging is characterized by a progressive decline in physiological functions, with energy metabolism playing a critical role. β-oxidation, the primary pathway for converting fatty acids into energy, is closely linked to aging and female reproductive senescence. Current approaches often fail to address the systemic metabolic dysfunction associated with aging, particularly menopause dyslipidemia, insulin resistance, and NAFLD. This study investigates how ovarian tissue influences hepatic proteins central to the β-oxidation pathway, aiming to uncover novel therapeutic targets.

Researchers analyzed liver proteomes from CBA/J control mice at 4, 13, 23, and 27 months of age. These were compared to 23-month-old mice that received transplants of young ovarian tissue at 13 months of age. β-oxidation proteins were quantified using high-resolution mass spectrometry. Serum triglycerides were measured enzymatically, and metabolic cage analyses were performed to assess substrate utilization and energy balance. The control arm consisted of age-matched mice without ovarian tissue transplantation, allowing for direct comparison of age-related changes versus intervention effects.

Ovarian tissue transplantation substantially modulates the expression of β-oxidation-related proteins and reduces systemic lipid accumulation in aged mice. These proteomic shifts were consistent with enhanced metabolic efficiency and decreased oxidative stress, mechanisms well-established as drivers of extended health span and longevity. The observed changes are highly relevant to menopause dyslipidemia, insulin resistance, metabolic syndrome, and NAFLD. Specifically, the transplants led to a reduction in β-oxidation proteins and triglycerides. This indicates an improvement in hepatic lipid clearance and a reduced risk of steatosis. The study identified that ovarian-derived signals induce metabolic reprogramming, characterized by these beneficial changes. These findings provide a molecular framework for how ovarian-derived factors may govern metabolic health. The observed proteomic changes align with the effects of known modulators such as PPARα agonists, CPT1 modulators, mitochondria-targeted antioxidants like MitoQ, and pathways involving NAD+ and sirtuins.