Cell reports (Cambridge), 2020-12, Vol.33 (13), p.108550-108550, Article 108550
2020
Details
- Autor(en) / Beteiligte
- Titel
- KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver
- Ist Teil von
- Cell reports (Cambridge), 2020-12, Vol.33 (13), p.108550-108550, Article 108550
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- 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. [Display omitted] •KLF10 expression is downregulated in mouse CD4+ T cells and human subjects with obesity•KLF10 deletion in mouse CD4+ T cells leads to multiple defects in CD4+ Treg function•Decreased TGF-β3 release from these Tregs alters glucose uptake and production•WT Treg delivery rescues obesity, insulin resistance, and fatty liver in these mice Immune cell accumulation in adipose tissues and liver contributes to the development of insulin resistance and obesity. Wara et al. demonstrate that the transcription factor KLF10 is a critical regulator of CD4+ T regulatory cell accumulation in liver and adipose depots, leading to obesity, insulin resistance, and fatty liver.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2020.108550Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7816773
- Format
- –
- Schlagworte
- Adipose Tissue - metabolism, Animals, CD4+ T cell, Cells, Cultured, Early Growth Response Transcription Factors - genetics, Early Growth Response Transcription Factors - metabolism, Fatty Liver - genetics, Fatty Liver - metabolism, Female, Gene Expression Regulation, Genetic Predisposition to Disease, glycolysis, Humans, Inflammation - metabolism, Insulin Resistance, KLF10, Kruppel-Like Transcription Factors - genetics, Kruppel-Like Transcription Factors - metabolism, Liver - metabolism, Male, metabolic disorders, Mice, Mice, Inbred C57BL, Mice, Knockout, mitochondria, Mitochondria - metabolism, obesity, Obesity - genetics, Obesity - metabolism, oxidative phosphorylation, Phosphatidylinositol 3-Kinase - metabolism, PI3K-Akt-mTOR pathway, Signal Transduction, T-Lymphocytes, Regulatory - metabolism, Transforming Growth Factor beta3 - metabolism, Treg