title: Mitochondria, body fat and type 2 diabetes: what is the connection?
abstract: This review will consider the concept that the development of a mitochondrial dysfunction in adipocytes is an early step in the pathogenesis for type 2 diabetes. Upon expansion of the adipose mass it becomes gradually inflamed and hypoxic. TNF-alpha, locally produced, induces insulin resistance of adipocytes leading to enhanced lipolysis. The excess of fatty acids, in combination with local hypoxia, results in the induction of mitochondrial damage in the adipocytes. As a result of this decline in mitochondrial activity less fatty acids can be removed within adipocytes by uncoupled mitochondrial beta-oxidation and by re-esterification, as mitochondrial activity provides substrates for glyceroneogenesis. As a result these fatty acids redistribute to other compartments of the body where they are stored as ectopic triglyceride deposits. This situation is associated with the development of insulin resistance of the liver and muscle. Furthermore, it contributes to damage the pancreatic beta-cells. Ultimately, this situation results in the development of a hyperglycemic state.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands. j.a.maassen@lumc.nl
authors.forename: J A
authors.initials: JA
authors.lastname: Maasen
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue; D000818:Animals; D015687:Cell Hypoxia; D004272:DNA, Mitochondrial / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D008066:Lipolysis; D008099:Liver / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D005227:Fatty Acids