title: Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids.
abstract: Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid-induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation-induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes.
authors.affiliation: Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Hafizi Abu Bakar
authors.affiliation: Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia.
authors.forename: Cheng
authors.initials: C
authors.lastname: Kian Kai
authors.affiliation: Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia.
authors.forename: Wan Najihah
authors.initials: WN
authors.lastname: Wan Hassan
authors.affiliation: Institute of Bioproduct Development, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia.
authors.forename: Mohamad Roji
authors.initials: MR
authors.lastname: Sarmidi
authors.affiliation: Institute of Bioproduct Development, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia.
authors.forename: Harisun
authors.initials: H
authors.lastname: Yaakob
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Clinical Investigation Centre, 13th Floor Main Tower, University Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Hasniza
authors.initials: H
authors.lastname: Zaman Huri
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D050171:Dyslipidemias / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007249:Inflammation; D007333:Insulin Resistance; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D017382:Reactive Oxygen Species
keywords: inflammation; insulin resistance; lipotoxicity; long chain fatty acids; mitochondrial dysfunction; reactive oxygen species