Paternal high‐fat diet transgenerationally impacts hepatic immunometabolism

What is it about?

The liver is a major organ that plays an essential role in regulating whole body metabolism. Under several pathophysiological conditions, including type 2 diabetes, obesity and non-alcoholic fatty liver disease, the metabolism of glucose, fat and protein is impaired in liver. Moreover, obesity and type 2 diabetes alter the expression of genes controlling glucose and lipids in liver through an epigenetic mechanism. Epigenetic changes involve systematic changes in gene expression that are not attributable to mutational changes in the underlying DNA. Here we determined the impact of metabolic disease on liver gene expression over several generations. We tested the hypothesis that in liver, gene expression profiles and metabolism are epigenetically programmed throughout several generation and that these responses are affected by the paternal diet. Our results support the notion that paternal lifestyle, including diet consumption prior to conception, transgenerationally programs whole-body and tissue-specific features of the offspring. We found that paternal diet affects the immunometabolic state of liver in second-generation offspring. The liver inflammatory response is altered in female rats from obese grandfathers fed diet rich in fats. Homeostatic inflammatory processes in liver are essential to maintain tissue and whole-body metabolism, and when disturbed, drives pathological processes associated with obesity and organ damage. Considering the close relationship between inflammation and metabolism, our findings indicate that the health of the offspring is profoundly affected by the macronutrient content of the grandpaternal diet.

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