Reduced Compensatory β-Cell Proliferation in Nfatc3-Deficient Mice Fed on High-Fat Diet.

Exp Clin Endocrinol Diabetes

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Published: September 2021

Background: High-fat-diet induces pancreatic β-cell compensatory proliferation, and impairments in pancreatic β-cell proliferation and function can lead to defects in insulin secretion and diabetes. NFATc3 is important for HFD-induced adipose tissue inflammation. But it is unknown whether NFATc3 is required for β cell compensatory growth in mice fed with HFD.

Methods: NFATc3 mRNA and protein expression levels were quantified by RT-qPCR and Western blotting, respectively, in pancreatic islets of WT mice fed on HFD for 12-20 weeks. Adenoviral-mediated overexpression of NFATc3 were conducted in Min6 cells and cultured primary mouse islets. NFATc3-/- mice and WT control mice were fed with HFD and metabolic and functional parameters were measured.

Results: We observed that the NFATc3 expression level was reduced in the islets of high-fat-diet (HFD)-fed mice. Adenovirus-mediated overexpression of NFATc3 enhanced glucose-stimulated insulin secretion and β-cell gene expression in cultured primary mouse islets. Nfatc3-/- mice initially developed similar glucose tolerance at 2-4 weeks after HFD feeding than HFD-fed WT mice, but Nfatc3-/- mice developed improved glucose tolerance and insulin sensitivity after 8 weeks of HFD feeding compared to Nfatc3+/+fed with HFD. Furthermore, Nfatc3-/- mice on HFD exhibited decreased β-cell mass and reduced expression of genes important for β-cell proliferation and function compared to Nfatc3+/+mice on HFD.

Conclusions: The findings suggested that NFATc3 plays a role in maintaining the pancreatic β-cell compensatory growth and gene expression in response to obesity.

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1008-9110DOI Listing

Publication Analysis

Top Keywords

mice fed
16
nfatc3-/- mice
16
β-cell proliferation
12
pancreatic β-cell
12
mice
10
β-cell compensatory
8
proliferation function
8
insulin secretion
8
compensatory growth
8
fed hfd
8

Similar Publications

Background: The current study investigated the effects of high-fat diet on acute response to 3,4-methylenedioxypyrovalerone (MDPV) in mice. MDPV is a beta-cathinone derivative endowed with psychostimulant activity. Similarly to recreational substances, consumption of palatable food stimulates the mesolimbic dopaminergic system, resulting in neuroadaptive changes.

View Article and Find Full Text PDF

Introduction: Malnutrition correlates with neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD); however, the potential mechanism underlying this association remains unclear.

Methods: Baseline and longitudinal associations of nutritional status with NPSs were analyzed in 374 patients on the AD continuum and 61 healthy controls. Serum biomarkers, behavioral tests, cerebral neurotransmitters, and differentially gene expression were evaluated in standard and malnourished diet-fed transgenic APPswe/PSEN1dE9 (APP/PS1) mice.

View Article and Find Full Text PDF

Background: Bone marrow inflammaging is a low-grade chronic inflammation that induces bone marrow aging. Multiple age-related and inflammatory diseases involve bone marrow inflammaging. Whether common pathological pathways exist in bone marrow inflammaging remains unclear.

View Article and Find Full Text PDF

The incidence of obesity is increasing annually worldwide. A high-fat diet (HFD) causes intestinal barrier damage, but effective interventions are currently unavailable. Our previous work demonstrated the therapeutic effect of nobiletin on obese mice; thus, we hypothesized that nobiletin could reverse HFD-induced damage to the intestinal barrier.

View Article and Find Full Text PDF

Metabolic syndrome is, in humans, associated with alterations in the composition and localization of the intestinal microbiota, including encroachment of bacteria within the colon's inner mucus layer. Possible promoters of these events include dietary emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate-80 (P80), which, in mice, result in altered microbiota composition, encroachment, low-grade inflammation and metabolic syndrome. While assessments of gut microbiota composition have largely focused on fecal/luminal samples, we hypothesize an outsized role for changes in mucus microbiota in driving low-grade inflammation and its consequences.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!