The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action

Abstract We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. f...

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Autores principales: Piotr Zabielski, Hady Razak Hady, Marta Chacinska, Kamila Roszczyc, Jan Gorski, Agnieszka U. Blachnio-Zabielska
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/5fb8112e54cc4da4bfa842370b38a71b
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spelling oai:doaj.org-article:5fb8112e54cc4da4bfa842370b38a71b2021-12-02T15:07:45ZThe effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action10.1038/s41598-018-25397-62045-2322https://doaj.org/article/5fb8112e54cc4da4bfa842370b38a71b2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25397-6https://doaj.org/toc/2045-2322Abstract We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. fed HFD and 3. fed HFD and treated with metformin. The animals were infused with a [U-13C]palmitate to measure fractional lipid synthesis rate. This allowed for the calculation of fractional synthesis rate of signaling lipids (FSR) through the estimation of their isotopic enrichment. Liver ceramide (Cer), diacylglycerol (DAG) and acyl-carnitine concentration and enrichment were analyzed by LC/MS/MS. The content of proteins involved in lipid metabolism and insulin signaling were analyzed by Western Blot. HFD treatment increased the content and FSR of DAG and Cer in the liver which was accompanied by systemic insulin resistance and inhibition of hepatic insulin signaling pathway under insulin stimulation. Metformin treatment ameliorated systemic insulin resistance and augmented the hepatic insulin signaling cascade. It reduced both the concentration and FSR of Cer, DAG, and increased acyl-carnitine content and the expression of mitochondrial markers. We postulate, that in liver, the insulin sensitizing effect of metformin depends on augmentation of mitochondrial β-oxidation, which protects from hepatic accumulation of both the Cer and DAG and preserves insulin sensitivity under HFD consumption. Moreover, we showed that hepatic content of Cer and DAG corresponds with their respective FSR.Piotr ZabielskiHady Razak HadyMarta ChacinskaKamila RoszczycJan GorskiAgnieszka U. Blachnio-ZabielskaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Piotr Zabielski
Hady Razak Hady
Marta Chacinska
Kamila Roszczyc
Jan Gorski
Agnieszka U. Blachnio-Zabielska
The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
description Abstract We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. fed HFD and 3. fed HFD and treated with metformin. The animals were infused with a [U-13C]palmitate to measure fractional lipid synthesis rate. This allowed for the calculation of fractional synthesis rate of signaling lipids (FSR) through the estimation of their isotopic enrichment. Liver ceramide (Cer), diacylglycerol (DAG) and acyl-carnitine concentration and enrichment were analyzed by LC/MS/MS. The content of proteins involved in lipid metabolism and insulin signaling were analyzed by Western Blot. HFD treatment increased the content and FSR of DAG and Cer in the liver which was accompanied by systemic insulin resistance and inhibition of hepatic insulin signaling pathway under insulin stimulation. Metformin treatment ameliorated systemic insulin resistance and augmented the hepatic insulin signaling cascade. It reduced both the concentration and FSR of Cer, DAG, and increased acyl-carnitine content and the expression of mitochondrial markers. We postulate, that in liver, the insulin sensitizing effect of metformin depends on augmentation of mitochondrial β-oxidation, which protects from hepatic accumulation of both the Cer and DAG and preserves insulin sensitivity under HFD consumption. Moreover, we showed that hepatic content of Cer and DAG corresponds with their respective FSR.
format article
author Piotr Zabielski
Hady Razak Hady
Marta Chacinska
Kamila Roszczyc
Jan Gorski
Agnieszka U. Blachnio-Zabielska
author_facet Piotr Zabielski
Hady Razak Hady
Marta Chacinska
Kamila Roszczyc
Jan Gorski
Agnieszka U. Blachnio-Zabielska
author_sort Piotr Zabielski
title The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
title_short The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
title_full The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
title_fullStr The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
title_full_unstemmed The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
title_sort effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/5fb8112e54cc4da4bfa842370b38a71b
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