Pleiotrophina novel modulator of the metabolic activity of the liver.

Résumé

Ageing and pregnancy are two physiological situations associated with metainflammation and insulin resistance. Pleiotrophin regulates lipid turnover, energetic homeostasis, insulin sensitivity and adipose tissue plasticity. We hypothesise that pleiotrophin could modulate the metabolic adaptations that take place in the liver during late pregnancy and ageing. To corroborate our hypothesis, we used female pleiotrophin Knock out mice and their respective controls (Wild type) at 3, 6, 12 and 15 months of age (ageing model) or on day 18 of pregnancy. Pleiotrophin deletion is associated with a reduced body and liver weight, lower hepatic lipid accumulation, and glucose intolerance. On the other hand, we have demonstrated a regulatory role for pleiotrophin in mitochondrial function and biogenesis in the liver and a role for glycerol kinase in regulating glucose homeostasis during pregnancy. Pleiotrophin is essential in maintaining hepatic lipid and glucose metabolism, and deletion of pleiotrophin averts ectopic fat accumulation in the liver and protects against the development of steatosis.