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

Abstract : 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.
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https://www.hal.inserm.fr/inserm-03462002
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Submitted on : Wednesday, December 1, 2021 - 3:50:09 PM
Last modification on : Sunday, June 26, 2022 - 5:58:42 AM
Long-term archiving on: : Wednesday, March 2, 2022 - 7:51:20 PM

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Marie Maraninchi, Anastasia Calabrese, Juan-Patricio Nogueira, Frédéric Castinetti, Julien Mancini, et al.. Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism. Journal of clinical lipidology, Elsevier, 2021, S1933-2874 (21), pp.00123-9. ⟨10.1016/j.jacl.2021.08.003⟩. ⟨inserm-03462002⟩

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