Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway

Background Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear. Methods Male C57BL/6J mice...

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Autores principales:	Jung-Hee Hong, Moon-Kyu Lee
Formato:	article
Lenguaje:	EN
Publicado:	Korean Diabetes Association 2021
Materias:	carnitine o-acetyltransferase diet, high-fat insulin resistance Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/e7974e25cf044320b8fed8c2c29f9501
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spelling	oai:doaj.org-article:e7974e25cf044320b8fed8c2c29f95012021-12-01T05:07:51ZCarnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway2233-60792233-608710.4093/dmj.2020.0223https://doaj.org/article/e7974e25cf044320b8fed8c2c29f95012021-11-01T00:00:00Zhttp://www.e-dmj.org/upload/pdf/dmj-2020-0223.pdfhttps://doaj.org/toc/2233-6079https://doaj.org/toc/2233-6087Background Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear. Methods Male C57BL/6J mice were divided into four groups: normal-fat diet, high-fat diet, a high-fat diet supplemented with intraperitoneal injection of (500 mg or 2,000 mg/kg/day) Godex for 8 weeks. Computed tomography, indirect calorimetry, and histological analyses including electron microscopy of the liver were performed, and biochemical profiles and oral glucose tolerance test and insulin tolerance test were undertaken. Expressions of genes in the lipid and glucose metabolism, activities of oxidative phosphorylation enzymes, carnitine acetyltransferase, pyruvate dehydrogenase, and acetyl-coenzyme A (CoA)/CoA ratio were evaluated. Results Godex improved insulin sensitivity and significantly decreased fasting plasma glucose, homeostatic model assessment for insulin resistance, steatosis, and gluconeogenesis, with a marked increase in fatty acid oxidation as well as better use of glucose in high-fat diet-fed mice. It preserved mitochondrial function and ultrastructure, restored oxidative phosphorylation enzyme activities, decreased acetyl-CoA/CoA ratio, and increased carnitine acetyltransferase content and pyruvate dehydrogenase activity. Carnitine acetyltransferase knockdown partially reversed the effects of Godex in liver and in vitro. Conclusion Godex improved insulin resistance and steatosis by regulating carnitine acetyltransferase in liver in high-fat diet-fed mice.Jung-Hee HongMoon-Kyu LeeKorean Diabetes Associationarticlecarnitine o-acetyltransferasediet, high-fatinsulin resistanceDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENDiabetes & Metabolism Journal, Vol 45, Iss 6, Pp 933-947 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	carnitine o-acetyltransferase diet, high-fat insulin resistance Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	carnitine o-acetyltransferase diet, high-fat insulin resistance Diseases of the endocrine glands. Clinical endocrinology RC648-665 Jung-Hee Hong Moon-Kyu Lee Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
description	Background Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear. Methods Male C57BL/6J mice were divided into four groups: normal-fat diet, high-fat diet, a high-fat diet supplemented with intraperitoneal injection of (500 mg or 2,000 mg/kg/day) Godex for 8 weeks. Computed tomography, indirect calorimetry, and histological analyses including electron microscopy of the liver were performed, and biochemical profiles and oral glucose tolerance test and insulin tolerance test were undertaken. Expressions of genes in the lipid and glucose metabolism, activities of oxidative phosphorylation enzymes, carnitine acetyltransferase, pyruvate dehydrogenase, and acetyl-coenzyme A (CoA)/CoA ratio were evaluated. Results Godex improved insulin sensitivity and significantly decreased fasting plasma glucose, homeostatic model assessment for insulin resistance, steatosis, and gluconeogenesis, with a marked increase in fatty acid oxidation as well as better use of glucose in high-fat diet-fed mice. It preserved mitochondrial function and ultrastructure, restored oxidative phosphorylation enzyme activities, decreased acetyl-CoA/CoA ratio, and increased carnitine acetyltransferase content and pyruvate dehydrogenase activity. Carnitine acetyltransferase knockdown partially reversed the effects of Godex in liver and in vitro. Conclusion Godex improved insulin resistance and steatosis by regulating carnitine acetyltransferase in liver in high-fat diet-fed mice.
format	article
author	Jung-Hee Hong Moon-Kyu Lee
author_facet	Jung-Hee Hong Moon-Kyu Lee
author_sort	Jung-Hee Hong
title	Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
title_short	Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
title_full	Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
title_fullStr	Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
title_full_unstemmed	Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
title_sort	carnitine orotate complex ameliorates insulin resistance and hepatic steatosis through carnitine acetyltransferase pathway
publisher	Korean Diabetes Association
publishDate	2021
url	https://doaj.org/article/e7974e25cf044320b8fed8c2c29f9501
work_keys_str_mv	AT jungheehong carnitineorotatecomplexamelioratesinsulinresistanceandhepaticsteatosisthroughcarnitineacetyltransferasepathway AT moonkyulee carnitineorotatecomplexamelioratesinsulinresistanceandhepaticsteatosisthroughcarnitineacetyltransferasepathway
_version_	1718405574883803136

Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway

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