X Liu1, J Y Huh1, H Gong1, J P Chamberland1,2, M T Brinkoetter1, O-P R Hamnvik2, C S Mantzoros1,2. 1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND/ OBJECTIVES: 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.
BACKGROUND/ OBJECTIVES: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 proteinUCP-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: P Krinninger; R Ensenauer; K Ehlers; K Rauh; J Stoll; S Krauss-Etschmann; H Hauner; H Laumen Journal: J Clin Endocrinol Metab Date: 2014-02-25 Impact factor: 5.958
Authors: Yifu Qiu; Khoa D Nguyen; Justin I Odegaard; Xiaojin Cui; Xiaoyu Tian; Richard M Locksley; Richard D Palmiter; Ajay Chawla Journal: Cell Date: 2014-06-05 Impact factor: 41.582
Authors: Rajesh R Rao; Jonathan Z Long; James P White; Katrin J Svensson; Jesse Lou; Isha Lokurkar; Mark P Jedrychowski; Jorge L Ruas; Christiane D Wrann; James C Lo; Donny M Camera; Jenn Lachey; Steven Gygi; Jasbir Seehra; John A Hawley; Bruce M Spiegelman Journal: Cell Date: 2014-06-05 Impact factor: 41.582
Authors: Lianne van Beek; Mirjam A Lips; Annemieke Visser; Hanno Pijl; Andreea Ioan-Facsinay; René Toes; Frits J Berends; Ko Willems van Dijk; Frits Koning; Vanessa van Harmelen Journal: Metabolism Date: 2013-12-10 Impact factor: 8.694
Authors: Kwang Dong Kim; Jie Zhao; Sogyong Auh; Xuanming Yang; Peishuang Du; Hong Tang; Yang-Xin Fu Journal: Nat Med Date: 2007-09-23 Impact factor: 53.440
Authors: Sung-Jun Park; Oksana Gavrilova; Alexandra L Brown; Jamie E Soto; Shannon Bremner; Jeonghan Kim; Xihui Xu; Shutong Yang; Jee-Hyun Um; Lauren G Koch; Steven L Britton; Richard L Lieber; Andrew Philp; Keith Baar; Steven G Kohama; E Dale Abel; Myung K Kim; Jay H Chung Journal: Cell Metab Date: 2017-05-02 Impact factor: 27.287
Authors: Xiaowen Liu; Nikolaos Perakakis; Huizhi Gong; John P Chamberland; Mary T Brinkoetter; Ole-Petter R Hamnvik; Christos S Mantzoros Journal: Metabolism Date: 2016-09-22 Impact factor: 8.694
Authors: Maria E Moreno-Fernandez; Daniel A Giles; Jarren R Oates; Calvin C Chan; Michelle S M A Damen; Jessica R Doll; Traci E Stankiewicz; Xiaoting Chen; Kashish Chetal; Rebekah Karns; Matthew T Weirauch; Lindsey Romick-Rosendale; Stavra A Xanthakos; Rachel Sheridan; Sara Szabo; Amy S Shah; Michael A Helmrath; Thomas H Inge; Hitesh Deshmukh; Nathan Salomonis; Senad Divanovic Journal: Cell Metab Date: 2021-05-17 Impact factor: 31.373
Authors: Michelle L Maugham; Patrick B Thomas; Gabrielle J Crisp; Lisa K Philp; Esha T Shah; Adrian C Herington; Chen Chen; Laura S Gregory; Colleen C Nelson; Inge Seim; Penny L Jeffery; Lisa K Chopin Journal: Sci Rep Date: 2017-03-28 Impact factor: 4.379
Authors: Emily A Teslow; Cristina Mitrea; Bin Bao; Ramzi M Mohammad; Lisa A Polin; Greg Dyson; Kristen S Purrington; Aliccia Bollig-Fischer Journal: Mol Oncol Date: 2019-03-01 Impact factor: 6.603