title: High-fat diet induces toll-like receptor 4-dependent macrophage/microglial cell activation and retinal impairment.
abstract: OBJECTIVE
  The toll-like receptor 4 (TLR4) signaling pathway is involved in chronic inflammation and insulin resistance, which are associated with obesity and diabetes mellitus. In the present study, a model of high-fat diet (HFD) feeding of mice was used to investigate the role of TLR4 in overnutrition- and obesity-associated inflammation and infiltration of macrophages and microglia in the retina.
  
  
  METHODS
  Wild-type C57BL/6 and TLR4 knockout (TLR4KO; B6.B10ScN-Tlr4(lps-del)/JthJ) mice were fed a HFD or control chow diet (CD) for 6 months. The TLR4 expression, the relative increase in macrophages/microglia (CD11b(+) and CD45(+) cells), the presence of markers of oxidative stress (gp91phox and malondialdehyde; MDA), and DNA damage (phosphorylated histone H2AX; γH2AX) were assessed by real-time PCR and immunofluorescence studies.
  
  
  RESULTS
  The HFD for 6 months showed increased obesity, glucose intolerance, and insulin resistance in mice. Toll-like receptor 4 expression was found in vascular pericytes at the inner retina. Increased CD11b(+) and CD45(+) cells, phosphorylated NF-κB, interleukin-6, gp91phox, MDA, and γH2AX were observed in the retina of mice fed a HFD compared to CD counterparts. TLR4KO mice did not show the adverse effects of HFD.
  
  
  CONCLUSIONS
  Our results indicate that HFD-induced macrophage/microglial cell activation and retinal impairment were reduced in the absence of TLR4. The findings suggest that TLR4 is implicated in the pathogenesis of retinal diseases caused by metabolic disorders.
authors.affiliation: Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2The Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Jong-Jer
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Nuclear Medicine, Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: I-Hui
authors.initials: IH
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chia-Shiang
authors.initials: CS
authors.lastname: Chang
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wu
authors.affiliation: The Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan 4Department of Surgery, Division of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Ka.
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005455:Fluorescent Antibody Technique; D018149:Glucose Intolerance; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4