Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis
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 se...
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MDPI AG
2022-12-01
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author | Anaïs Alves Frédéric Lamarche Rémy Lefebvre Eva Drevet Mulard Arthur Bassot Stéphanie Chanon Emmanuelle Loizon Claudie Pinteur Aline Maria Nunes de Lira Gomes Bloise Murielle Godet Gilles J. P. Rautureau Baptiste Panthu Béatrice Morio |
author_facet | Anaïs Alves Frédéric Lamarche Rémy Lefebvre Eva Drevet Mulard Arthur Bassot Stéphanie Chanon Emmanuelle Loizon Claudie Pinteur Aline Maria Nunes de Lira Gomes Bloise Murielle Godet Gilles J. P. Rautureau Baptiste Panthu Béatrice Morio |
author_sort | Anaïs Alves |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-1caf037b23b34c5eb14f69c6d72b61372023-12-02T00:45:53ZengMDPI AGNutrients2072-66432022-12-011519610.3390/nu15010096Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver GluconeogenesisAnaïs Alves0Frédéric Lamarche1Rémy Lefebvre2Eva Drevet Mulard3Arthur Bassot4Stéphanie Chanon5Emmanuelle Loizon6Claudie Pinteur7Aline Maria Nunes de Lira Gomes Bloise8Murielle Godet9Gilles J. P. Rautureau10Baptiste Panthu11Béatrice Morio12CarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceLaboratory of Fundamental and Applied Bioenergetics, INSERM U1055, Université Grenoble Alpes, 38400 Saint Martin d’Hères, FranceCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceICBMS CNRS U5246, Université Claude Bernard Lyon 1, Université de Lyon, 69622 Villeurbanne, FranceErika Cosset Team, Cancer Research Centre of Lyon, UMR INSERM U1052/CNRS 5286, 69008 Lyon, FranceCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceDepartment of Physical Education and Sport Sciences, Laboratory of Nutrition, Physical Activity and Phenotypic Plasticity, Universidade Federal de Pernambuco, UFPE, 55604-000 Vitória de Santo Antão, PE, BrazilCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceICBMS CNRS U5246, Université Claude Bernard Lyon 1, Université de Lyon, 69622 Villeurbanne, FranceCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceCarMeN laboratory, UMR INSERM U1060/INRAE U1397, Université Claude Bernard Lyon 1, Université de Lyon, 69310 Pierre-Bénite, FranceInteractions 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.https://www.mdpi.com/2072-6643/15/1/96dietary supplementamino acid metabolismobesity-related metabolic disordersinsulin resistancemitochondria |
spellingShingle | Anaïs Alves Frédéric Lamarche Rémy Lefebvre Eva Drevet Mulard Arthur Bassot Stéphanie Chanon Emmanuelle Loizon Claudie Pinteur Aline Maria Nunes de Lira Gomes Bloise Murielle Godet Gilles J. P. Rautureau Baptiste Panthu Béatrice Morio Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis Nutrients dietary supplement amino acid metabolism obesity-related metabolic disorders insulin resistance mitochondria |
title | Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis |
title_full | Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis |
title_fullStr | Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis |
title_full_unstemmed | Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis |
title_short | Glycine Supplementation in Obesity Worsens Glucose Intolerance through Enhanced Liver Gluconeogenesis |
title_sort | glycine supplementation in obesity worsens glucose intolerance through enhanced liver gluconeogenesis |
topic | dietary supplement amino acid metabolism obesity-related metabolic disorders insulin resistance mitochondria |
url | https://www.mdpi.com/2072-6643/15/1/96 |
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