Cellular and Molecular Life Sciences

, Volume 74, Issue 7, pp 1231–1245 | Cite as

The obesity-related pathology and Th17 cells

  • Yusuke Endo
  • Koutaro Yokote
  • Toshinori NakayamaEmail author


Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases. We herein outline the developing principles in the control of T cell differentiation and function via their cellular metabolism. Also discussed are recent findings that changes in the intracellular metabolism, including fatty acid metabolism, affect the Th17 cell function in obese individuals. Finally, we will also highlight the unique molecular mechanism involved in the activation of retinoid-related orphan receptor-gamma-t (RORγt) by intracellular metabolism and discuss a new therapeutic approach for treating autoimmune disorders through the inhibition of RORγt.


Obesity Chronic inflammation Th17 cells ACC1 Fatty acid metabolism RORγt activation 



Retinoid-related orphan receptor-gamma-t


Helper T cell


Adipose tissue macrophages


Visceral adipose tissue


Subcutaneous adipose tissue


Group 2 innate lymphoid cells


Multiple sclerosis, psoriasis


Inflammatory bowel disease


Rheumatoid arthritis


Matrix metalloproteases


Stromal vascular cells


Diphtheria toxin receptor


Mesenchymal stem cell


Central nervous system


Genome-wide association study


Oxidative phosphorylation


Transcription factor signal transducer and activator


Basic leucine zipper transcription factor ATF-like


Interferon-regulatory factor


Sterol regulatory element-binding protein


Estrogen related receptor-alpha


Liver X receptor


Fatty acid oxidation


Steroid receptor coactivator 1 (SRC-1)

Dig (dhd)


Dig (sal)



Chromatin immunoprecipitation


Cholesterol biosynthetic intermediates



This work was supported by the Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment), and by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) (Grants-in-Aid: for Scientific Research (S) #26221305, (B) #21390147 and #26293165, Young Scientists [A] #16H06224, and (B) #24790461, Challenging Exploratory Research #26670362 and #23659240, Grant-in-Aid for Scientific Research on Innovative Areas #16H01352, and Scientific Research on Innovative Areas ‘Stem Cell Aging’ #26115009), the Ministry of Health, Labor and Welfare, The Astellas Foundation for Research on Metabolic Disorders, The Uehara Memorial Foundation, Osaka Foundation for Promotion of Fundamental Medical Research, Kanae Foundation for the Promotion of Medical Science, Princes Takamatsu Cancer Research Fund and Takeda Science Foundation.


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Yusuke Endo
    • 1
  • Koutaro Yokote
    • 2
  • Toshinori Nakayama
    • 1
    • 3
    Email author
  1. 1.Department of Immunology, Graduate School of MedicineChiba UniversityChibaJapan
  2. 2.Department of Clinical Cell Biology and Medicine, Graduate School of MedicineChiba UniversityChibaJapan
  3. 3.AMED-CREST, AMEDChibaJapan

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