Developmental Programming of Obesity and Liver Metabolism by Maternal Perinatal Nutrition Involves the Melanocortin System
Language English Country Switzerland Media electronic
Document type Journal Article
Grant support
FS/10/003/28163
British Heart Foundation - United Kingdom
PubMed
28930194
PubMed Central
PMC5622801
DOI
10.3390/nu9091041
PII: nu9091041
Knihovny.cz E-resources
- 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
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.
Center for Translational Medicine International Clinical Research Center Brno 65691 Czech Republic
Department of Pathology University College London London WC1E 6JJ UK
Institute for Liver and Digestive Health University College London London NW3 2PF UK
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