title: Regulation of diet-induced adipose tissue and systemic inflammation by salicylates and pioglitazone.
abstract: It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6C(hi)), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes.
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ; Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: Myung-Sunny
authors.initials: MS
authors.lastname: Kim
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ; Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kamei
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Libin
authors.initials: L
authors.lastname: Liu
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kristin
authors.initials: K
authors.lastname: Moore
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ju Rang
authors.initials: JR
authors.lastname: Woo
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shoelson
authors.affiliation: The Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jongsoon
authors.initials: J
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D002452:Cell Count; D059305:Diet, High-Fat; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D007333:Insulin Resistance; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D005810:Multigene Family; D009765:Obesity / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D000077205:Pioglitazone; D012459:Salicylates / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D012459:Salicylates; D045162:Thiazolidinediones; D000077205:Pioglitazone