Potential Role of Leptin in Cardiac Steatosis Induced by Highly Saturated Fat Intake during Adolescence

Scope To identify the age‐dependent effect of diets containing elevated amounts of either saturated or unsaturated fatty acids on cardiac steatosis in mice. Methods and Results Five‐ and eight‐week‐old C57BL/6J mice cohorts are given free access to either a saturated or an unsaturated fatty‐acid‐enriched diet during 8 weeks. Body weight (BW) and food intake are monitored during this period. Cardiac lipid content, carnitine palmitoyltransferase‐I (CPT‐I) activity, and the amount of uncoupling proteins 2 and 3 (UCP2 and UCP3) are analyzed and correlated with blood leptin concentration. Leptin and PPARγ gene expression is quantified in white adipose tissue (WAT). Both diets have a similar effect on food intake, BW, and adiposity, independently of the age. Nevertheless, cardiac steatosis is specifically identified in adolescent mice consuming the saturated diet. These animals also display lower activity of cardiac CPT‐I, a down‐regulation of cardiac UCP2, together with lower concentration of plasma leptin. Accordingly, leptin gene expression is reduced in the visceral WAT. Conclusion Consumption of diets containing elevated amounts of saturated fat during adolescence and early adult life promotes cardiac steatosis in mice. An insufficient endocrine activity of WAT, in terms of leptin production, may account for such an effect. Adolescent and adult mice that consumed either a saturated‐oil‐enriched food (SOLF) or an unsaturated‐oil‐enriched food (UOLF) develop robust hyperleptinemia, with the exception of adolescent mice consuming SOLF. These animals display cardiac steatosis, which might be related to a low activity of cardiac carnitine palmitoyltransferase and a deficient mitochondrial uncoupling associated with low leptin levels.