Developmental Programming of Obesity and Liver Metabolism by Maternal Perinatal Nutrition Involves the Melanocortin...

Area of Science:

• Metabolic disorders
• Genetics
• Hepatology

Background:

• Maternal obesity is linked to offspring metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD).
• Melanocortin-4 receptor (Mc4r) gene deficiency is associated with adult obesity.
• Perinatal diet exposure can program long-term metabolic health in offspring.

Purpose of the Study:

• To investigate the impact of Mc4r gene deficiency on offspring liver health under conditions of maternal obesogenic feeding.
• To understand the interplay between perinatal diet and Mc4r genotype in programming metabolic dysfunction.

Main Methods:

• Mice heterozygous for Mc4r were fed control or obesogenic diets during gestation and lactation.
• Offspring were grouped by genotype (wild type vs. Mc4r knockout) and maternal diet.
• Phenotypic, biochemical, histological, and gene expression analyses were performed on offspring at 6 months.

Main Results:

• Mc4r knockout offspring exhibited increased body, liver, and adipose tissue weights compared to wild types.
• Mild hepatic steatosis was observed in control Mc4r knockout offspring.
• Absence of Mc4r upregulated hepatic genes related to inflammation, fibrosis, and immune cell infiltration.

Conclusions:

• Maternal obesogenic diet during the perinatal period programs offspring obesity.
• The Mc4r system plays a crucial role in mediating the effects of maternal obesity on offspring liver health.
• Mc4r deficiency exacerbates diet-induced metabolic and hepatic changes in offspring.