Effects of paternal obesity and diet intervention on offspring phenotype in mice

Abstract

Emerging evidence indicates that obesity and metabolic dysfunction–associated steatotic liver disease (MASLD) may be transmitted from father to offspring through non-genetic mechanisms. Various preconception interventions have been proposed, but only few have studied a simple dietary intervention. The aim of this thesis was to study if high-fat diet (HFD) -induced obesity and hepatic steatosis in C57BL6/N mice are transmitted from fathers to male offspring, and if so, to assess whether this can be prevented by treating the father’s obesity with a diet intervention. The F0 males were first fed an HFD for 8 weeks (F0-H), after which half were changed back to chow for 6 weeks (F0-HC / diet intervention), while controls were fed chow (F0-C), and all were mated with chow-fed females. The F1 males were fed chow until 10 weeks of age and then half were fed an HFD for 10 weeks. Body composition, glucose tolerance, liver and plasma lipids, and hepatic gene expression were assessed. We found that both chow-fed F0-HC and F0-H offspring gained more weight than controls, and F0-HC offspring showed impaired glucose tolerance. Although liver and plasma lipid levels were similar across groups, the hepatic gene expression profile in F0-HC offspring was notably altered compared to F0-C and F0-H, underlying the need for further study to assess the biological significance of these changes. Importantly, HFD-fed F0-HC offspring gained less body weight and fat mass and had lower liver and plasma cholesterol than F0-H offspring, showing that paternal diet intervention could protect the offspring from the deleterious effects of paternal obesity.