Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO). At 21 days, offspring were genotyped, weaned onto a control diet, and sacrificed at 6 months old. Offspring phenotypic characteristics, plasma biochemical profile, liver histology, and hepatic gene expression were analyzed. Mc4r_ko offspring showed higher body, liver and adipose tissue weights respect to the wild type animals. Histological examination showed mild hepatic steatosis in offspring group C_KO. The expression of hepatic genes involved in regulating inflammation, fibrosis, and immune cell infiltration were upregulated by the absence of the Mc4r gene. These results demonstrate that maternal obesogenic feeding during the perinatal period programs offspring obesity development with involvement of the Mc4r system.

• Keywords
• Non-Alcoholic Fatty Liver Disease, developmental programming, intra-abdominal fat, maternal nutrition, obesity,
• MeSH
• Alanine Transaminase blood   MeSH
• Aspartate Aminotransferases blood   MeSH
• Maternal Nutritional Physiological Phenomena * MeSH
• Liver metabolism   MeSH
• Blood Glucose metabolism   MeSH
• Disease Models, Animal MeSH
• Mice, Knockout MeSH
• Mice, Obese MeSH
• Mice MeSH
• Obesity genetics   MeSH
• Perinatal Care MeSH
• Receptor, Melanocortin, Type 4 deficiency   genetics   MeSH
• Gene Expression Regulation MeSH
• Pregnancy MeSH
• Triglycerides blood   MeSH
• Prenatal Exposure Delayed Effects genetics   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alanine Transaminase MeSH
• Aspartate Aminotransferases MeSH
• Blood Glucose MeSH
• MC4R protein, mouse MeSH Browser
• Receptor, Melanocortin, Type 4 MeSH
• Triglycerides MeSH