Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus

Abstract Berberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac...

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Main Authors: Laura K. Cole, Genevieve C. Sparagna, Marilyne Vandel, Bo Xiang, Vernon W. Dolinsky, Grant M. Hatch
Format: Article
Language:English
Published: Nature Publishing Group 2021-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-95353-4
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spelling doaj-b4c4b65b3b994db5bc6e62dfd3f8fc692021-08-08T11:24:31ZengNature Publishing GroupScientific Reports2045-23222021-08-011111810.1038/s41598-021-95353-4Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitusLaura K. Cole0Genevieve C. Sparagna1Marilyne Vandel2Bo Xiang3Vernon W. Dolinsky4Grant M. Hatch5Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Department of Pharmacology and Therapeutics, Children’s Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of ManitobaDivision of Cardiology, Department of Medicine, University of Colorado Anschutz Medical CenterDiabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Department of Pharmacology and Therapeutics, Children’s Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of ManitobaDiabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Department of Pharmacology and Therapeutics, Children’s Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of ManitobaDiabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Department of Pharmacology and Therapeutics, Children’s Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of ManitobaDiabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Department of Pharmacology and Therapeutics, Children’s Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of ManitobaAbstract Berberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.https://doi.org/10.1038/s41598-021-95353-4
collection DOAJ
language English
format Article
sources DOAJ
author Laura K. Cole
Genevieve C. Sparagna
Marilyne Vandel
Bo Xiang
Vernon W. Dolinsky
Grant M. Hatch
spellingShingle Laura K. Cole
Genevieve C. Sparagna
Marilyne Vandel
Bo Xiang
Vernon W. Dolinsky
Grant M. Hatch
Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
Scientific Reports
author_facet Laura K. Cole
Genevieve C. Sparagna
Marilyne Vandel
Bo Xiang
Vernon W. Dolinsky
Grant M. Hatch
author_sort Laura K. Cole
title Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
title_short Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
title_full Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
title_fullStr Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
title_full_unstemmed Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
title_sort berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-08-01
description Abstract Berberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.
url https://doi.org/10.1038/s41598-021-95353-4
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