title: Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet.
abstract: OBJECTIVE
  Obesity is characterized by chronic inflammation and immune dysregulation, as well as insulin resistance, but the link between obesity and adaptive immunity remains to be fully studied.
  
  
  METHODS
  To elucidate the role of adaptive immunity on body composition, glucose homeostasis and inflammation, recombination-activating gene 1 knockout (Rag1-/-) mice, without mature T-lymphocytes or B-lymphocytes, were maintained on a low- or high-fat diet (LFD and HFD, respectively) for 11 weeks.
  
  
  RESULTS
  Rag1-/- mice fed HFD gained significantly more weight and had increased body fat compared with wild type. Downregulation of energy expenditure as well as brown fat uncoupling protein UCP-1 and UCP-3 gene expression were noticed in HFD-fed Rag1-/- mice compared with LFD. HFD mice had significantly decreased energy intake compared with LFD mice, consistent with decreased agouti-related protein and increased pro-opiomelanocortin gene expression levels in the hypothalamus. Moreover, compared with wild type, Rag1-/- mice had lower interleukin (IL)-4 levels, a cytokine recently found to induce browning in white adipocytes, and higher IL-12 levels in HFD-fed Rag1-/- mice. Despite that HFD Rag1-/- mice were more obese, they had similar glucose, insulin and adiponectin levels, while leptin was marginally increased.
  
  
  CONCLUSIONS
  Mice with deficiency in adaptive immunity are obese, partly owing to decreased energy expenditure, but are metabolically normal, suggesting that mature lymphocytes have necessary roles in the development of obesity-related metabolic dysregulation.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Huh
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gong
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Chamberland
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Brinkoetter
authors.affiliation: Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
authors.forename: O-P R
authors.initials: OP
authors.lastname: Hamnvik
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000378:metabolism*; D007031:Hypothalamus / Q000473:pathology*; D007249:Inflammation; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology*
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; C064658:RAG-1 protein