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The mechanics of the liver, a receptor history

Liver activity is highly dependent on lifestyle and food intake

The mechanics of the liver, a receptor history
Toxalim's "Integrative Toxicology and Metabolism" team investigates dietary and environmental factors that influence lipid metabolism and its role in liver diseases, taking into account sex-related differences to better adapt prevention against metabolic and inflammatory diseases.

The activity of the liver has specificities in men and women, i.e.sexual dimorphism. In addition, the appearance of certain liver diseases is very dependent on gender. This is particularly the case for metabolic diseases, including non-alcoholic metabolic hepatopathies (liver diseases), which represent a global public health issue. In the early stages of these diseases, hepatocytes accumulate abnormally high levels of lipids in the liver, which can promote progression to serious stages: hepatitis, cirrhosis, cancer.

  •      Dialogue between adipose tissue and liver: an identified mechanism

The transcription factor "Peroxisome Proliferator Activated Receptor" or PPARα, is an essential player in hepatocyte metabolism where it controls the expression of hundreds of genes. Recent work by the team, in collaboration with researchers from other organizations and universities, indicates that it plays a central role in the interactions between adipose tissue and the liver, brought into play during metabolic stress. This receptor is located in the nucleus of hepatocytes. It regulates the expression of genes coding for enzymes that limit the degradation of lipids from adipose tissue (adipocyte lipolysis) and the synthesis of ketone bodies.

  •      A role in metabolic liver disease and sexual dimorphism

These researchers also analyzed hepatic regulators of adaptation to diets favoring the onset of liver disease in each sex. Among the factors involved in this sexual dimorphism, the researchers proved that the PPARα receptor is one of the main determinants of hepatic sex-linked differences in mice. This is also the case in patients, men and women, with chronic non-alcoholic liver diseases.

  •      PPARα being the target of many drugs in development and also of environmental contaminants (endocrine and metabolic disruptors), these results illustrate the importance of taking into consideration the metabolic dialogues between organs and the specificities linked to gender in the fields of health and of medicine.

Read the full article on the INRAE national website (in French)

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