@article{36852faa42a6489f8864c1d98dae0cb8,
title = "KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver",
abstract = "CD4+ T cells regulate inflammation and metabolism in obesity. An imbalance of CD4+ T regulatory cells (Tregs) is critical in the development of insulin resistance and diabetes. Although cytokine control of this process is well understood, transcriptional regulation is not. KLF10, a member of the Kruppel-like transcription factor family, is an emerging regulator of immune cell function. We generated CD4+-T-cell-specific KLF10 knockout (TKO) mice and identified a predisposition to obesity, insulin resistance, and fatty liver due to defects of CD4+ Treg mobilization to liver and adipose tissue depots and decreased transforming growth factor β3 (TGF-β3) release in vitro and in vivo. Adoptive transfer of wild-type CD4+ Tregs fully rescued obesity, insulin resistance, and fatty liver. Mechanistically, TKO Tregs exhibit reduced mitochondrial respiration and glycolysis, phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR signaling, and consequently impaired chemotactic properties. Collectively, our study identifies CD4+ T cell KLF10 as an essential regulator of obesity and insulin resistance by altering Treg metabolism and mobilization.",
keywords = "CD4 T cell, KLF10, PI3K-Akt-mTOR pathway, Treg, glycolysis, metabolic disorders, mitochondria, obesity, oxidative phosphorylation",
author = "Wara, {Akm Khyrul} and Shijia Wang and Chun Wu and Fang Fang and Stefan Haemmig and Weber, {Brittany N.} and Aydogan, {Ceren O.} and Yevgenia Tesmenitsky and Hassan Aliakbarian and Hawse, {John R.} and Malayannan Subramaniam and Lei Zhao and Sage, {Peter T.} and Ali Tavakkoli and Amanda Garza and Lydia Lynch and Banks, {Alexander S.} and Feinberg, {Mark W.}",
note = "Funding Information: We acknowledge Amir Mina (Brigham and Women{\textquoteright}s Hospital) and Ali Hashemi Gheinani (Boston Children{\textquoteright}s Hospital) for technical support. This work was supported by NIH grants ( HL115141 , HL134849 , HL148207 , HL148355 , and HL153356 to M.W.F.), the Arthur K. Watson Charitable Trust (to M.W.F.), the Dr. Ralph and Marian Falk Medical Research Trust , Bank of America , N.A. Trustee (to M.W.F.), American Heart Association grants 18SFRN33900144 and 20SFRN35200163 (to M.W.F.), and the Mayo Clinic Center for Biomedical Discovery (to J.R.H.). Funding Information: We acknowledge Amir Mina (Brigham and Women's Hospital) and Ali Hashemi Gheinani (Boston Children's Hospital) for technical support. This work was supported by NIH grants (HL115141, HL134849, HL148207, HL148355, and HL153356 to M.W.F.), the Arthur K. Watson Charitable Trust (to M.W.F.), the Dr. Ralph and Marian Falk Medical Research Trust, Bank of America, N.A. Trustee (to M.W.F.), American Heart Association grants 18SFRN33900144 and 20SFRN35200163 (to M.W.F.), and the Mayo Clinic Center for Biomedical Discovery (to J.R.H.). M.W.F. conceived the hypothesis; A.K.W. S.W. and M.W.F. designed the research; A.K.W. S.W. C.W. F.F. S.H. B.N.W. C.O.A. Y.T. A.S.B. and P.T.S. carried out the experiments; H.A. J.R.H. M.S. and A.T. contributed critical reagents; A.K.W. S.W. C.W. F.F. S.H. B.N.W. L.Z. P.T.S. A.S.B. and M.W.F analyzed and interpreted the data; and A.K.W. S.W. and M.W.F. wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = dec,
day = "29",
doi = "10.1016/j.celrep.2020.108550",
language = "English (US)",
volume = "33",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}