title: Direct and macrophage-mediated actions of fatty acids causing insulin resistance in muscle cells.
abstract: Obesity is associated with insulin resistance and increased risk for developing type 2 diabetes. Enlarged adipocytes develop resistance to the anti-lipolytic action of insulin. Elevated levels of fatty acids in the plasma and interstitial fluids lead to whole-body insulin resistance by disrupting normal insulin-regulated glucose uptake and glycogen storage in skeletal muscle. A new understanding has been cultivated in the past 5 to 10 years that adipocytes and macrophages (resident or bone marrow-derived) in adipose tissue of obese animals and humans are activated in a pro-inflammatory capacity and secrete insulin resistance-inducing factors. However, only recently have fatty acids themselves been identified as agents that engage toll-like receptors of the innate immunity systems of macrophages, adipocytes and muscle cells to trigger pro-inflammatory responses. This review summarizes our observations that fatty acids evoke the release of pro-inflammatory factors from macrophages that consequently induce insulin resistance in muscle cells.
authors: Cell Biology Program, The Hospital for Sick Children, Toronto, Canada.
authors: Phillip J
authors: PJ
authors: Bilan
authors: Victor
authors: V
authors: Samokhvalov
authors: Alexandra
authors: A
authors: Koshkina
authors: Jonathan D
authors: JD
authors: Schertzer
authors: M Constantine
authors: MC
authors: Samaan
authors: Amira
authors: A
authors: Klip
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance; D008264:Macrophages / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology
chemical_list: D005227:Fatty Acids