title: Fatty acid synthase: association with insulin resistance, type 2 diabetes, and cancer.
abstract: BACKGROUND
  An emerging paradigm supports the notion that deregulation of fatty acid synthase (FASN)-catalyzed de novo FA biogenesis could play a central role in the pathogenesis of metabolic diseases sharing the hallmark of insulin-resistance.
  
  
  BACKGROUND
  We reviewed pharmacological and genetic alterations of FASN activity that have been shown to significantly influence energy expenditure rates, fat mass, insulin sensitivity, and cancer risk. This new paradigm proposes that insulin-resistant conditions such as obesity, type 2 diabetes, and cancer arise from a common FASN-driven "lipogenic state". An important question then is whether the development or the progression of insulin-related metabolic disorders can be prevented or reversed by the modulation of FASN status. If we accept the paradigm of FASN dysfunction as a previously unrecognized link between insulin resistance, type 2 diabetes, and cancer, the use of insulin sensitizers in parallel with forthcoming FASN inhibitors should be a valuable therapeutic approach that, in association with lifestyle interventions, would concurrently improve energy-flux status, ameliorate insulin sensitivity, and alleviate the risk of lipogenic carcinomas.
  
  
  CONCLUSIONS
  Although the picture is currently incomplete and researchers in the field have plenty of work ahead, the latest clinical and experimental evidence that we discuss illuminates a functional and drug-modifiable link that connects FASN-driven endogenous FA biosynthesis, insulin action, and glucose homeostasis in the natural history of insulin-resistant pathologies.
authors.affiliation: Catalan Institute of Oncology, Girona Biomedical Research Institute, Hospital Universitari de Girona Josep Trueta, Girona, Catalonia, Spain. jmfernandezreal.girona.ics@gencat.cat
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Martin
authors.forename: Francisco Jose
authors.initials: FJ
authors.lastname: Ortega
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Fernandez-Real
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D064429:Fatty Acid Synthases / Q000737:chemistry / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D009369:Neoplasms / Q000201:enzymology*
chemical_list: D064429:Fatty Acid Synthases; D005947:Glucose