title: Fyn deficiency promotes a preferential increase in subcutaneous adipose tissue mass and decreased visceral adipose tissue inflammation.
abstract: Previous studies have demonstrated that Fyn knockout (FynKO) mice on a standard chow diet display increased glucose clearance and whole-body insulin sensitivity associated with decreased adiposity resulting from increased fatty acid use and energy expenditure. Surprisingly, however, despite a similar extent of adipose tissue (AT) mass accumulation on a high-fat diet, the FynKO mice remained fully glucose tolerant and insulin sensitive. Physiologic analyses demonstrated that the FynKO mice had a combination of skewed AT expansion into the subcutaneous compartment rather than to the visceral depot, reduced AT inflammation associated with reduced T-cell and macrophage infiltration, and increased proportion of anti-inflammatory M2 macrophages. These data demonstrate that Fyn is an important regulator of whole-body integrative metabolism that coordinates AT expansion, inflammation, and insulin sensitivity in states of nutrient excess. These data further suggest that inhibition of Fyn function may provide a novel target to prevent AT inflammation, insulin resistance, and the dyslipidemia components of the metabolic syndrome.
authors: Department of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors: Ting-Wen A
authors: TW
authors: Lee
authors: Hyokjoon
authors: H
authors: Kwon
authors: Haihong
authors: H
authors: Zong
authors: Eijiro
authors: E
authors: Yamada
authors: Manu
authors: M
authors: Vatish
authors: Jeffrey E
authors: JE
authors: Pessin
authors: Claire C
authors: CC
authors: Bastie
mesh_terms: D050154:Adiposity; D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D037102:Lectins; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases; C544448:Arg1 protein, mouse; D001119:Arginase