Reduced Compensatory β-Cell Proliferation in Nfatc3-Deficient Mice Fed on High-Fat Diet
Summary
Nuclear Factor of Activated T-cells 3 (NFATc3) is crucial for pancreatic beta-cell compensatory growth during high-fat-diet (HFD) induced obesity. Loss of NFATc3 impairs beta-cell proliferation and function, impacting insulin secretion.
Area of Science:
- Metabolic disease research
- Endocrinology
- Molecular biology
Background:
- High-fat diets (HFD) trigger pancreatic beta-cell proliferation to maintain glucose homeostasis.
- Impaired beta-cell function can lead to diabetes.
- Nuclear Factor of Activated T-cells 3 (NFATc3) is implicated in HFD-induced adipose tissue inflammation, but its role in beta-cell adaptation is unclear.
Purpose of the Study:
- To investigate the role of NFATc3 in pancreatic beta-cell compensatory growth in mice fed a HFD.
- To determine if NFATc3 is required for beta-cell adaptation to obesity.
Main Methods:
- Quantified NFATc3 mRNA and protein in islets of HFD-fed mice.
- Overexpressed NFATc3 in beta-cell lines and primary islets.
- Assessed metabolic and functional parameters in NFATc3 knockout and wild-type mice on HFD.
Main Results:
- NFATc3 expression was reduced in islets of HFD-fed mice.
- NFATc3 overexpression enhanced glucose-stimulated insulin secretion and beta-cell gene expression.
- NFATc3 knockout mice showed improved glucose tolerance and insulin sensitivity on HFD, with reduced beta-cell mass and proliferation markers.
Conclusions:
- NFATc3 is essential for maintaining pancreatic beta-cell compensatory growth and gene expression under HFD conditions.
- NFATc3 deficiency leads to impaired beta-cell adaptation to obesity.
