1. STAT3 Regulates Mitochondrial Gene Expression in Pancreatic β-Cells and Its Deficiency Induces Glucose Intolerance in Obesity.
- Author
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Schaschkow, Anaïs, Pang, Lokman, Vandenbempt, Valerie, Elvira, Bernat, Litwak, Sara A., Vekeriotaite, Beata, Maillard, Elisa, Vermeersch, Marjorie, Paula, Flavia M.M., Pinget, Michel, Perez-Morga, David, Gough, Daniel J., Gurzov, Esteban N., and Paula, Flavia Mm
- Subjects
STAT proteins ,GLUCOSE intolerance ,GENE expression ,HIGH-fat diet ,MITOCHONDRIA ,OBESITY ,RESEARCH ,ANIMAL experimentation ,RESEARCH methodology ,ANIMAL nutrition ,BLOOD sugar ,MEDICAL cooperation ,EVALUATION research ,ISLANDS of Langerhans ,INSULIN ,COMPARATIVE studies ,GENES ,CARRIER proteins ,MICE - Abstract
Most obese and insulin-resistant individuals do not develop diabetes. This is the result of the capacity of β-cells to adapt and produce enough insulin to cover the needs of the organism. The underlying mechanism of β-cell adaptation in obesity, however, remains unclear. Previous studies have suggested a role for STAT3 in mediating β-cell development and human glucose homeostasis, but little is known about STAT3 in β-cells in obesity. We observed enhanced cytoplasmic expression of STAT3 in severely obese subjects with diabetes. To address the functional role of STAT3 in adult β-cells, we generated mice with tamoxifen-inducible partial or full deletion of STAT3 in β-cells and fed them a high-fat diet before analysis. Interestingly, β-cell heterozygous and homozygous STAT3-deficient mice showed glucose intolerance when fed a high-fat diet. Gene expression analysis with RNA sequencing showed that reduced expression of mitochondrial genes in STAT3 knocked down human EndoC-β1H cells, confirmed in FACS-purified β-cells from obese STAT3-deficient mice. Moreover, silencing of STAT3 impaired mitochondria activity in EndoC-β1H cells and human islets, suggesting a mechanism for STAT3-modulated β-cell function. Our study postulates STAT3 as a novel regulator of β-cell function in obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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