Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism

Background: Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism. Objective: We aimed to examine the direct and/or indirect role of GH on TRL metabolism. Methods: We investigated the effect on fasting and postprandial hepatic-TRL and intestinal-TRL metabolism of short-term (one month) withdrawal of GH in 10 GH-deficient adults. Results: After GH withdrawal, we found a reduction in fasting plasma TRL concentration (significant decrease in TRL-TG, TRL-cholesterol, TRL-apoB-100, TRL-apoC-III and TRL-apoC-II) but not in postprandial TRL response. This reduction was due to fewer fasting TRL particles without a change in TG per particle and was not accompanied by a change in postprandial TRL-apoB-48 response. Individual reductions in TRL correlated strongly with increases in insulin sensitivity and decreases in TRL-apoC-III. Conclusion: In this relatively short term ‘loss of function’ human experimental model, we have shown an unanticipated reduction of hepatic-TRL particles despite increase in total body fat mass and reduction in lean mass. These findings contrast with the atherogenic dyslipidemia previously described in chronic GH deficient states, providing a new perspective for the role of GH in lipoprotein metabolism.Fil: Maraninchi, Marie. Inserm; FranciaFil: Calabrese, Anastasia. Inserm; FranciaFil: Nogueira, Juan Patricio. Universidad Nacional de Formosa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Castinetti, Frédéric. Inserm; FranciaFil: Mancini, Julien. Inserm; FranciaFil: Mourre, Florian. Inserm; FranciaFil: Piétri, Léa. Inserm; FranciaFil: Bénamo, Eric. Inserm; FranciaFil: Albarel, Frédérique. Inserm; FranciaFil: Morange, Isabelle. Inserm; FranciaFil: Dupont Roussel, Jeanine. Inserm; FranciaFil: Nicolay, Alain. La Conception Hospital; FranciaFil: Brue, Thierry. Inserm; FranciaFil: Béliard, Sophie. Inserm; FranciaFil: Valéro, René. Inserm; Franci