Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver

The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control di...

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Main Authors: Bodil Bjørndal, Tra-My Thi Le, Elin Strand, Lise Madsen, Rolf K. Berge
Format: Article
Language:English
Published: MDPI AG 2024-07-01
Series:SynBio
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Online Access:https://www.mdpi.com/2674-0583/2/3/14
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author Bodil Bjørndal
Tra-My Thi Le
Elin Strand
Lise Madsen
Rolf K. Berge
author_facet Bodil Bjørndal
Tra-My Thi Le
Elin Strand
Lise Madsen
Rolf K. Berge
author_sort Bodil Bjørndal
collection DOAJ
description The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (<i>p</i> < 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice.
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spelling doaj-art-daf230f786c5440eab4ea4a51ce135772025-08-20T01:55:52ZengMDPI AGSynBio2674-05832024-07-012324025310.3390/synbio2030014Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty LiverBodil Bjørndal0Tra-My Thi Le1Elin Strand2Lise Madsen3Rolf K. Berge4Department of Sport, Food and Natural Sciences, Western Norway University of Applied Sciences, 5020 Bergen, NorwayDepartment of Clinical Science, University of Bergen, 5020 Bergen, NorwayDepartment of Immunology and Transfusion Medicine, Haukeland University Hospital, 5021 Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, 5020 Bergen, NorwayDepartment of Clinical Science, University of Bergen, 5020 Bergen, NorwayThe antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (<i>p</i> < 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice.https://www.mdpi.com/2674-0583/2/3/14meldonium3-(2,2,2-trimethylhydrazinium)-propionatemetformin1,1-dimethylbiguanide hydrochloridehepatic steatosisnon-alcoholic fatty liver disease
spellingShingle Bodil Bjørndal
Tra-My Thi Le
Elin Strand
Lise Madsen
Rolf K. Berge
Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver
SynBio
meldonium
3-(2,2,2-trimethylhydrazinium)-propionate
metformin
1,1-dimethylbiguanide hydrochloride
hepatic steatosis
non-alcoholic fatty liver disease
title Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver
title_full Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver
title_fullStr Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver
title_full_unstemmed Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver
title_short Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver
title_sort metformin lowers plasma triacylglycerol levels in mice with impaired carnitine biosynthesis and fatty liver
topic meldonium
3-(2,2,2-trimethylhydrazinium)-propionate
metformin
1,1-dimethylbiguanide hydrochloride
hepatic steatosis
non-alcoholic fatty liver disease
url https://www.mdpi.com/2674-0583/2/3/14
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