Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-019-04623-y ORIGINAL ARTICLE High fat diet administration leads to the mitochondrial dysfunction and selectively alters the expression of class 1 GLUT protein in mice Dhruv Jha 1  · Papiya Mitra Mazumder 1 Received: 26 September 2018 / Accepted: 18 January 2019 © Springer Nature B.V. 2019 Abstract Metabolic syndrome is an agglomeration of disorders including obesity, diabetes and cardiovascular diseases and character- ized as chronic mild infammation which elevates the circulatory infammatory 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 efects 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 dysfunc- tion 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 signifcantly 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 signifcantly (p < 0.001) upregulated the GLUT 1 and 3 expressions while signifcant 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 Introduction Obesity is characterized as chronic mild inflammation which elevates the circulatory infammatory markers like the tumour necrosis factor (TNF-α),C-reactive protein (CRP- 1), interleukins (IL 4, IL6) and the plasminogen activating factor (PAI-1) [1, 2]. These changes are viewed as the pri- mary factor in the development and progression of metabolic disorders. The proposed hypothesis behind this includes * Dhruv Jha dhruvjha89@gmail.com Papiya Mitra Mazumder pmitramazumder@bitmesra.ac.in 1 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215, India