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High fat diet administration leads to the mitochondrial dysfunction and selectively alters the expression of class 1 GLUT protein in mice

  • Dhruv JhaEmail author
  • Papiya Mitra Mazumder
Original Article

Abstract

Metabolic syndrome is an agglomeration of disorders including obesity, diabetes and cardiovascular diseases and characterized as chronic mild inflammation which elevates the circulatory inflammatory markers. This could be due to mitochondrial dysfunction, oxidative stress and hypoxia as a consequence of high fat diet (HFD) intake. The present study focuses on the effects of HFD on lactate and mitochondrial metabolism as well as tissue dependent changes in glucose transporter (GLUT) expression in liver, skeletal muscles and adipose tissue of mouse. Lactate dehydrogenase (LDH) and mitochondrial dysfunction established the link between the occurrences of metabolic stress due to HFD. In this work, it was observed that chronic HFD administration aggravated the metabolic alterations by causing reduced ATP production, imbalanced oxidative stress and altered class 1 GLUTs expression. Chronic HFD significantly reduced (p < 0.001) the superoxide dismutase (SOD), catalase (CAT) activities alongside elevated liver injury markers AST and ALT. This in turn causes decreased ATP/ADP ratio, mitochondrial dysfunction and exacerbated LDH levels. This imbalance further led to altered GLUT expression in hepatic cells, adipose tissue and skeletal muscles. HFD significantly (p < 0.001) upregulated the GLUT 1 and 3 expressions while significant downregulated (p < 0.001) GLUT 2 and 4 expression in liver, skeletal muscles and white adipose tissue. These results revealed the link between class 1 GLUTs, mitochondrial dysfunction and HFD-induced metabolic disorder. It can be concluded that HFD impacts mitochondrial metabolism and reprograms tissue-dependent glucose transporter.

Keywords

High fat diet GLUT 1–4 Mitochondrial dysfunction LDH Liver Skeletal muscles White adipose tissue 

Abbreviations

HFD

High fat diet

STZ

Streptozotocin

GLUT

Glucose transporter

LDH

Lactate dehydrogenase

IL

Interleukins

CAT

Catalase

SOD

Superoxide dismutase

MDA

Malondialdehyde

AST

Aspartate transaminase

ALT

Alanine transaminase

HIF

Hypoxia inducible factor

ROS

Reactive oxygen species

OXPHOS

Oxidative phosphorylation

FFA

Free fatty acids

TNF

Tumour necrosis factor

SDH

Succinate dehydrogenase

WAT

White adipose tissue

NBT

Nitro blue tetrazolium

NAD

Nicotinamide adenine dinucleotide

i.p

Intraperitoneal

ATP

Adenosine triphosphate

ADP

Adenosine diphosphate

Notes

Acknowledgements

The authors would like to acknowledge Ms Parul Gupta and Mr Santosh Prajapati for technical help. Authors also acknowledge the Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology for providing the facilities. Authors are grateful to UGC for providing financial assistance.

Compliance with ethical standards

Conflict of interest

Authors declares no conflict of interest.

Ethical approval

All the experiments were approved by the Institutional Animal Ethics Committee (IAEC) of Birla Institute of Technology, Mesra (Reg. No. 1968/PO/Re/17/CPCSEA) as per Approval No. (BIT/PH/IAEC/15/2015) and the experiments were performed as per CPCSEA guidelines.

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences and TechnologyBirla Institute of TechnologyRanchiIndia

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