Kinetic study of the expression of genes related to hepatic steatosis, global intermediate metabolism and cellular stress during overfeeding in mule ducks
Induced 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 use via glycolysis and lipogenesis. Expression of cpt1a, acad, hadh suggested 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 of cyp2e1 suggesting that autophagy could be suppressed. Lamp2a and plin2 enhanced, conflicting with the idea of an inhibition of lipophagy. Hsbp1 overexpression indicated that mechanisms are carried out during overfeeding to limit cellular stress and apoptosis to prevent the switch to pathological state. Atf4 and asns overexpression 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.