Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis

Anaïs Alves (1) , Frédéric Lamarche (2) , Rémy Lefebvre (1) , Eva Drevet Mulard (3) , Arthur Bassot (4) , Stéphanie Chanon (1) , Emmanuelle Loizon (1) , Claudie Pinteur (1) , Aline Maria Nunes de Lira Gomes Bloise (5) , Murielle Godet (1) , Gilles J P Rautureau (3, 6) , Baptiste Panthu (1) , Béatrice Morio (1)

1 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
2 LBFA - Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée
3 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
4 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
5 UFRPE - Universidade Federal Rural de Pernambuco
6 CRMN - Centre de Résonance Magnetique Nucleaire

Interactions between mitochondria and the endoplasmic reticulum, known as MAMs, are altered in the liver in obesity, which contributes to disruption of the insulin signaling pathway. In addition, the plasma level of glycine is decreased in obesity, and the decrease is strongly correlated with the severity of insulin resistance. Certain nutrients have been shown to regulate MAMs; therefore, we tested whether glycine supplementation could reduce insulin resistance in the liver by promoting MAM integrity. Glycine (5 mM) supported MAM integrity and insulin response in primary rat hepatocytes cultured under control and lipotoxic (palmitate 500 µM) conditions for 18 h. In contrast, in C57 BL/6 JOlaHsd mice (male, 6 weeks old) fed a high-fat, high-sucrose diet (HFHS) for 16 weeks, glycine supplementation (300 mg/kg) in drinking water during the last 6 weeks (HFHS-Gly) did not reverse the deleterious impact of HFHS-feeding on liver MAM integrity. In addition, glycine supplementation worsened fasting glycemia and glycemic response to intraperitoneal pyruvate injection compared to HFHS. The adverse impact of glycine supplementation on hepatic gluconeogenesis was further supported by the higher oxaloacetate/acetyl-CoA ratio in the liver in HFHS-Gly compared to HFHS. Although glycine improves MAM integrity and insulin signaling in the hepatocyte in vitro, no beneficial effect was found on the overall metabolic profile of HFHS-Gly-fed mice.

Keywords: amino acid metabolism; obesity-related metabolic disorders; insulin resistance; mitochondria; dietary supplement

Domains: Life Sciences [q-bio]

Anaïs Alves, Frédéric Lamarche, Rémy Lefebvre, Eva Drevet Mulard, Arthur Bassot, et al.. Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis. Nutrients, 2023, 15 (1), pp.96. ⟨10.3390/nu15010096⟩. ⟨hal-03959235⟩