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Dietary Vitamin A Affects the Function of Incretin-Producing Enteroendocrine Cells in Male Mice Fed a High-Fat Diet. | LitMetric

AI Article Synopsis

  • Retinol-binding protein 2 (RBP2) is crucial for vitamin A transport in gut cells, and mice without it show obesity and glucose issues.
  • This study investigated how different vitamin A diets impact the function and gene expression of incretin-secreting cells in RBP2-deficient mice compared to controls.
  • Results indicated that RBP2 mice gained more weight and had elevated GIP levels on a normal vitamin A diet, while their GIP response decreased on a low vitamin A diet, highlighting RBP2's role in incretin regulation and gene expression related to enter endocrine cells.

Article Abstract

Background: Retinol-binding protein 2 (RBP2) is an intracellular carrier for vitamin A in the absorptive enterocytes. Mice lacking RBP2 (Rbp2) display an unexpected phenotype of obesity, glucose intolerance, and elevated glucose-dependent insulinotropic polypeptide (GIP) levels. GIP and glucagon-like peptide 1 (GLP-1) are incretin hormones secreted by enteroendocrine cells (EECs). We recently demonstrated the presence of RBP2 and other retinoid-related proteins in EECs.

Objectives: Given RBP2's role in intracellular retinoid trafficking, we aimed to evaluate whether dietary vitamin A affects incretin-secreting cell function and gene expression.

Methods: Male Rbp2 mice and sex- and age-matched controls (n = 6-9) were fed a high-fat diet (HFD) for 18 wk containing normal (VAN, 4000 IU/kg of diet) or low (VAL, 25% of normal) vitamin A concentrations. Body weight was recorded biweekly. Plasma GIP and GLP-1 levels were obtained fasting and 30 min after an oral fat gavage at week 16. Glucose tolerance tests were also performed. Mice were killed at week 18, and blood and tissue samples were obtained.

Results: Rbp2 mice displayed greater weight gain on the VAN compared with the VAL diet from week 7 of the intervention (P ≤ 0.01). Stimulated GIP levels were elevated in Rbp2 mice compared with their controls fed the VAN diet (P = 0.02), whereas their GIP response was lower when fed the VAL diet (P = 0.03). Although no differences in GLP-1 levels were observed in the VAN diet group, a lower GLP-1 response was seen in Rbp2 mice fed the VAL diet (P = 0.02). Changes in incretin gene expression and that of other genes associated with EEC lineage and function were consistent with these observations. Circulating and hepatic retinoid levels revealed no systemic vitamin A deficiency across dietary groups.

Conclusions: Our data support a role for RBP2 and dietary vitamin A in incretin secretion and gene expression in mice fed a HFD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613727PMC
http://dx.doi.org/10.1016/j.tjnut.2023.08.030DOI Listing

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