title: Gamma-tocotrienol attenuates high-fat diet-induced obesity and insulin resistance by inhibiting adipose inflammation and M1 macrophage recruitment.
abstract: OBJECTIVE
  We have previously demonstrated that gamma tocotrienol (γT3) potently inhibits adipocyte hyperplasia in human adipose-derived stem cells (hASCs). In this study, our objective was to investigate the γT3 effects on early-onset obesity, inflammation and insulin resistance in vivo.
  
  
  METHODS
  Young C57BL/6J mice were fed a high-fat (HF) diet supplemented with 0.05% γT3 for 4 weeks. The concentrations of γT3 in plasma and adipose tissue were measured using high-performance liquid chromatography. Effects of γT3 on body weight gain, adipose volume, plasma levels of fasting glucose, insulin (enzyme-linked immunosorbent assay (ELISA)), proinflammatory cytokines (mouse cytokine array), insulin signaling (western blotting) and gene expression (quantitative real-time PCR, qPCR) in the liver and adipose tissue were examined. Influences of γT3 on [3H]-2-deoxyglucose uptake and lipopolysaccharide (LPS)-mediated NFκB signaling (western blotting) were assessed in hASCs. Effects of γT3 on macrophage M1/M2 activation were investigated using qPCR in mouse bone marrow-derived macrophages.
  
  
  RESULTS
  After a 4-week treatment, γT3 accumulated in adipose tissue and reduced HF diet-induced weight gain in epididymal fat, mesenteric fat and the liver. Compared with HF diet-fed mice, HF+γT3-fed mice were associated with (1) decreased plasma levels of fasting glucose, insulin and proinflammatory cytokines, (2) improved glucose tolerance and (3) enhanced insulin signaling in adipose tissue. There were substantial decreases in macrophage specific markers, and monocyte chemoattractant protein-1, indicating that γT3 reduced the recruitment of adipose tissue macrophages (ATMs). In addition, γT3 treatment in human adipocytes resulted in (1) activation of insulin-stimulated glucose uptake and (2) a significant suppression of MAP kinase and NFκB activation. In parallel, γT3 treatment led to a reduction of LPS-mediated M1 macrophage polarization.
  
  
  CONCLUSIONS
  Our results demonstrated that γT3 ameliorates HF diet-mediated obesity and insulin resistance by inhibiting systemic and adipose inflammation, as well as ATM recruitment.
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 1] Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA [2] Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: I
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lee
authors.affiliation: Department of Surgery, College of Medicine, University of Nebraska, Omaha, NE, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Hollins
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Marshall
authors.affiliation: 1] Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA [2] Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chung
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002839:Chromans / Q000378:metabolism / Q000494:pharmacology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D007333:Insulin Resistance; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D060888:Real-Time Polymerase Chain Reaction; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D002839:Chromans; D014810:Vitamin E; C013649:plastochromanol 8