title: T-lymphocyte responses to intestinally absorbed antigens can contribute to adipose tissue inflammation and glucose intolerance during high fat feeding.
abstract: BACKGROUND
  Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.
  
  
  RESULTS
  Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, in a chylomicron-dependent manner. Absorption tended to be higher in mesenteric than subcutaneous adipose tissue, and was lowest in gonadal tissue. OVA immunoreactivity was detected in stromal vascular cells, including endothelial cells. In OVA-sensitized mice, OVA feeding caused marked accumulation of CD3+ and osteopontin+ cells in mesenteric adipose tissue. The accumulating T-lymphocytes were mainly CD4+. As expected, high-fat (60% kCal) diets promoted mesenteric adipose tissue inflammation compared to low-fat diets (10% Kcal), as reflected by increased expression of osteopontin and interferon-gamma. Immune responses to dietary OVA further increased diet-induced osteopontin and interferon-gamma expression in mesenteric adipose. Inflammatory gene expression in subcutaneous tissue did not respond significantly to OVA or dietary fat content. Lastly, whereas OVA responses did not significantly affect bodyweight or adiposity, they significantly impaired glucose tolerance.
  
  
  CONCLUSIONS
  Our results suggest that loss or lack of immunological tolerance to intestinally absorbed T-lymphocyte antigens can contribute to mesenteric adipose tissue inflammation and defective glucose metabolism during high-fat dieting.
authors.affiliation: Graduate Center for Nutritional Sciences and Internal Medicine Department, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianing
authors.initials: J
authors.lastname: Li
authors.forename: Lihua
authors.initials: L
authors.lastname: Tang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.forename: Willem
authors.initials: W
authors.lastname: de Villiers
authors.forename: Erik
authors.initials: E
authors.lastname: Eckhardt
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018149:Glucose Intolerance / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D004041:Dietary Fats; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007457:Iodine Radioisotopes; D053495:Osteopontin; D010047:Ovalbumin