title: B cell-activating factor controls the production of adipokines and induces insulin resistance.
abstract: Visceral adipose tissue (VAT) inflammation has been linked to the pathogenesis of insulin resistance and metabolic syndrome. VAT has recently been established as a new component of the immune system and is involved in the production of various adipokines and cytokines. These molecules contribute to inducing and accelerating systemic insulin resistance. In this report, we investigated the role of B cell-activating factor (BAFF) in the induction of insulin resistance. We investigated BAFF levels in the sera and VAT of obese mice. In obese mice, the BAFF levels were preferentially increased in VAT and sera compared to these levels in normal control mice. Next, we treated mice with BAFF to analyze its influence on insulin sensitivity. BAFF impaired insulin sensitivity in normal mice. Finally, we investigated the mechanisms underlying insulin resistance induced by BAFF in adipocytes. BAFF also induced alterations in the expression levels of genes related to insulin resistance in adipocytes. In addition, BAFF directly affected the glucose uptake and phosphorylation of insulin receptor substrate-1 in adipocytes. We propose that autocrine or paracrine BAFF and BAFF-receptor (BAFF-R) interaction in VAT leads to impaired insulin sensitivity via inhibition of insulin signaling pathways and alterations in adipokine production.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Hamada
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.forename: Teruki
authors.initials: T
authors.lastname: Miyake
authors.forename: Keitarou
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Fujimasa
authors.initials: F
authors.lastname: Tada
authors.forename: Shinya
authors.initials: S
authors.lastname: Furukawa
authors.forename: Bunzo
authors.initials: B
authors.lastname: Matsuura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000096:biosynthesis*; D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D053264:B-Cell Activating Factor; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D005947:Glucose