title: Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice.
abstract: The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against diet-induced obesity and associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice against obesity and obesity-associated insulin resistance and dyslipidemia without food consumption being affected. Tb attenuated the production of TNFα and IL-1β by peritoneal macrophages and their expression in adipose tissue. Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and infiltration by leukocytes and restored the production of adiponectin. These effects were associated with a partial reversion of hepatic steatosis, reduction in liver and skeletal muscle content of phosphorylated JNK, and an improvement in muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the beneficial effects of Tb are likely to be secondary to the reduction in body weight, we also found direct protective actions of butyrate reducing TNFα production after LPS injection and in vitro by LPS- or palmitic acid-stimulated macrophages and attenuating lipolysis in vitro and in vivo. The results, reported herein, suggest that Tb may be useful for the treatment and prevention of obesity-related metabolic disorders.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Avenida Prof. Lineu Prestes, 1524, 05508-900, Butantã, Sao Paulo, SP, Brazil. mramirez@icb.usp.br
authors.forename: Marco Aurélio Ramirez
authors.initials: MA
authors.lastname: Vinolo
authors.forename: Hosana G
authors.initials: HG
authors.lastname: Rodrigues
authors.forename: William T
authors.initials: WT
authors.lastname: Festuccia
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Crisma
authors.forename: Vitor S
authors.initials: VS
authors.lastname: Alves
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Martins
authors.forename: Catia L
authors.initials: CL
authors.lastname: Amaral
authors.forename: Jarlei
authors.initials: J
authors.lastname: Fiamoncini
authors.forename: Sandro M
authors.initials: SM
authors.lastname: Hirabara
authors.forename: Fabio T
authors.initials: FT
authors.lastname: Sato
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Fock
authors.forename: Gabriella
authors.initials: G
authors.lastname: Malheiros
authors.forename: Marinilce F
authors.initials: MF
authors.lastname: dos Santos
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000096:biosynthesis; D008055:Lipids / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D014280:Triglycerides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D008055:Lipids; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C005830:tributyrin