A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis.

ABSTRACT: Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity. Our results unveil a sex-dependent phenotypic remodeling beyond liver damage. Males, more than females, show fasting hypoglycemia and increased insulin sensitivity. They exhibit diastolic dysfunction, remodeling of the circulating lipoproteins and cardiac lipidome. Conversely, females do not manifest cardiac dysfunction but exhibit cardiometabolic impairments supported by impaired mitochondrial integrity and β-oxidation, remodeli

SUBMITTER: Burelle C 

PROVIDER: S-EPMC10959946 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature