Small litter size attenuates adverse hepatic effects induced by a high-sucrose diet.

We evaluated whether metabolic imprinting (MI) induced by small litter size (SL) could mitigate liver damage, redox imbalance, and NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation caused by a high-sucrose diet (HSD) in young rats. Male Wistar rats (P0) were divided into control litters (CL; 8 pups/dam) and SLs (4 pups/dam). After weaning, they were fed for 8 weeks with a standard diet (STD) or HSD (30% sucrose), and distributed into four groups: STD-CL, HSD-CL, STD-SL, and HSD-SL. After euthanasia, blood and liver samples were collected for analysis. The HSD impaired hepatic insulin signaling and promoted hepatic alterations associated with NLRP3 inflammasome activation. Although the HSD increased antioxidant enzyme activity, it also altered the nonalcoholic fatty liver disease activity score (NAS) and elevated oxidative damage. SL-induced MI attenuated oxidative stress, as evidenced by reduced p47phox(Ser359) expression and decreased hepatic protein and lipid oxidation, potentially modulating the interaction between the experimental variables and p-AKT(Ser473). In addition, SL attenuated NLRP3 inflammasome activation and decreased caspase-1 and IL-18 levels. This study provides novel evidence that SL-induced MI attenuates adverse hepatic changes, oxidative stress, and NLRP3 inflammasome activation promoted by HSD. Our findings not only challenge the current literature but also suggest that SL-induced metabolic plasticity enables adaptations to post-weaning dietary variations, thereby mitigating hepatic damage induced by a post-weaning HSD in young rats.