title: CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice.
abstract: OBJECTIVE
  Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown.
  
  
  METHODS
  During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions.
  
  
  RESULTS
  Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation.
  
  
  CONCLUSIONS
  Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: M
authors.initials: M
authors.lastname: Poggi
authors.affiliation: 1] Inserm, U1068, CRCM, Marseilles, France [2] Institut Paoli-Calmettes, Marseilles, France [3] Aix-Marseille Université, UM 105, Marseilles, France [4] CNRS, UMR7258, CRCM, Marseilles, France.
authors.forename: S O
authors.initials: SO
authors.lastname: Morin
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: D
authors.initials: D
authors.lastname: Bastelica
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: R
authors.initials: R
authors.lastname: Govers
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: M
authors.initials: M
authors.lastname: Canault
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: D
authors.initials: D
authors.lastname: Bernot
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: O
authors.initials: O
authors.lastname: Georgelin
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: M
authors.initials: M
authors.lastname: Verdier
authors.affiliation: 1] Inserm, U1048, Toulouse, France [2] Université Paul Sabatier, IMC, Toulouse Cedex 4, France.
authors.forename: R
authors.initials: R
authors.lastname: Burcelin
authors.affiliation: 1] Inserm, U1068, CRCM, Marseilles, France [2] Institut Paoli-Calmettes, Marseilles, France [3] Aix-Marseille Université, UM 105, Marseilles, France [4] CNRS, UMR7258, CRCM, Marseilles, France.
authors.forename: D
authors.initials: D
authors.lastname: Olive
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: M-C
authors.initials: MC
authors.lastname: Alessi
authors.affiliation: 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France.
authors.forename: F
authors.initials: F
authors.lastname: Peiretti
authors.affiliation: 1] Inserm, U1068, CRCM, Marseilles, France [2] Institut Paoli-Calmettes, Marseilles, France [3] Aix-Marseille Université, UM 105, Marseilles, France [4] CNRS, UMR7258, CRCM, Marseilles, France.
authors.forename: J A
authors.initials: JA
authors.lastname: Nunès
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D018106:CD28 Antigens / Q000235:genetics*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology*; D017353:Gene Deletion; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000473:pathology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D018106:CD28 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7