A murine model of gestational diabetes reveals MASLD risk and alterations in markers of hepatic mitochondrial metabolism.

Introduction: Gestational Diabetes Mellitus (GDM) impacts roughly 1 in 7 pregnancies and results in metabolic dysfunction-associated steatotic liver disease (MASLD) in 30% of these women. Nonetheless, there exists a dearth of investigation into the relationship between GDM and MASLD. Here, we sought to investigate the potential role of hepatic mitochondrial function in GDM and MASLD. Methods: One week prior to conception and throughout pregnancy, mice were fed either a low-fat control diet (CD) or a high-fat, high-sucrose (HFHS) diet to induce an established model of GDM. Maternal livers were collected at day 0, 6.5, 13.5 and 17.5 of pregnancy. Hepatic markers (via mRNA and western blot analyses) of mitochondrial biogenesis, autophagy, mitophagy, activity, and function were assessed, as well as markers of inflammation and antioxidant status were evaluated. Results: Progressing gestation in both CD and GDM dams significantly decreased protein and mRNA markers of hepatic mitochondrial biogenesis ( Discussion: Pregnancy, independent of diet, decreased markers of liver mitochondrial biogenesis, autophagy, and mitophagy in dams. The GDM mouse model exhibited elevated hepatic TG and NAS, as well as decreased liver mitochondrial activity. These findings demonstrate that pregnancy and GDM significantly impact maternal liver mitochondrial metabolism and unveil new insight on the potential relationship between MASLD and GDM.