Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-018-4551-7 ORIGINAL ARTICLE Cytosolic lipid excess-induced mitochondrial dysfunction is the cause or efect of high fat diet-induced skeletal muscle insulin resistance: a molecular insight Baishali Alok Jana 1  · Pavan Kumar Chintamaneni 2  · Praveen Thaggikuppe Krishnamurthy 2  · Ashish Wadhwani 1  · Suresh Kumar Mohankumar 3 Received: 21 May 2018 / Accepted: 30 November 2018 © Springer Nature B.V. 2018 Abstract Mitochondria play a central role in the energy homeostasis in eukaryotic cells by generating ATP via oxidative metabo- lism of nutrients. Excess lipid accumulation and impairments in mitochondrial function have been considered as putative mechanisms for the pathogenesis of skeletal muscle insulin resistance. Accumulation of lipids in tissues occurs due to either excessive fatty acid uptake, decreased fatty acid utilization or both. Consequently, elevated levels cytosolic lipid metabo- lites, triglycerides, diacylglycerol and ceramides have been demonstrated to adversely afect glucose homeostasis. Several recent studies indicate that reduced insulin-stimulated ATP synthesis and reduced expression of mitochondrial enzymes and PPAR-γ coactivator, in high fat feeding (lipid overload) are associated with insulin resistance. Despite the fact, few notable studies suggest mitochondrial dysfunction is prevalent in type 2 diabetes mellitus; it is still not clear whether the defects in mitochondrial function are the cause of insulin resistance or the consequential efects of insulin resistance itself. Thus, there is a growing interest in understanding the intricacies of mitochondrial function and its association with cytosolic lipid excess. This review therefore critically examines the molecular cascades linking cytosolic lipid excess and mitochondrial dysfunction in the pathogenesis of high fat diet-induced insulin resistance in skeletal muscle. Baishali Alok Jana and Pavan Kumar Chintamaneni have contributed equally to this work. * Suresh Kumar Mohankumar suresh.jsscpo@jssuni.edu.in Baishali Alok Jana bjphd@jssuni.edu.in Pavan Kumar Chintamaneni chpkpkd@jssuni.edu.in Praveen Thaggikuppe Krishnamurthy praveentk@jssuni.edu.in Ashish Wadhwani dradwadhwani@jssuni.edu.in 1 Department of Pharmaceutical Biotechnology, JSS College of Pharmacy (A Constituent College of JSS Academy of Higher Education & Research, Mysuru, Karnataka, India), Ootacamund, Tamil Nadu 643001, India 2 Department of Pharmacology, JSS College of Pharmacy (A Constituent College of JSS Academy of Higher Education & Research, Mysuru, Karnataka, India), Ootacamund, Tamil Nadu 643001, India 3 Department of Pharmacognosy & Phytopharmacy, TIFAC CORE in Herbal Drugs, JSS College of Pharmacy (A Constituent College of JSS Academy of Higher Education & Research, Mysuru, Karnataka, India), P.B. 20, Rocklands, Ootacamund, Tamil Nadu 643001, India