Kinetic study of the expression of genes related to hepatic steatosis, global intermediate metabolism and cellular stress during overfeeding in mule ducks

Abstract

ABSTRACTInduced by overfeeding, hepatic steatosis is a reversible process exploited for “foie gras” production. To better understand the mechanisms underlying this non-pathological phenomenon, we analysed the physiological responses of the mule duck to cope with 22 carbohydrate meals. A kinetic analysis of intermediate metabolism and cell protection mechanisms was performed during overfeeding. As expected, dietary carbohydrates are up taken mainly by the liver (chrebp, glut1/2/8) and converted into lipids (acox, scd1, acsl1, fas, dgat2). Our study showed an activation of cholesterol biosynthetic pathway with significant correlations between plasma cholesterol, expression of key genes (hmgcr, soat1) and liver weight. Results revealed an activation of insulin and amino acid cell signalling pathway suggesting that ducks boost insulin sensitivity to raise glucose uptake and useviaglycolysis and lipogenesis. Expression ofcpt1a, acad, hadhsuggested an induction of beta-oxidation probably to remove part of newly synthesized lipids and avoid lipotoxicity. Cellular stress analysis revealed an upregulation of autophagy-related gene expression (atg8, atg9, sqstm1) in contrast with an induction ofcyp2e1suggesting that autophagy could be suppressed.Lamp2aandplin2enhanced, conflicting with the idea of an inhibition of lipophagy.Hsbp1overexpression indicated that mechanisms are carried out during overfeeding to limit cellular stress and apoptosis to prevent the switch to pathological state.Atf4andasnsoverexpression reflects the nutritional imbalance during overfeeding. These results permitted to highlight the mechanisms enabling mule ducks to efficiently handle the huge starch overload and reveal potential biomarker candidates of hepatic steatosis as plasma cholesterol for liver weight.