ArticleThe Journal of nutrition2025
Dietary Fat Intake Attenuates Vitamin A Deficiency-Associated Elastic Fiber Remodeling and Lipid Reduction in the Alveolar Niche in Mice.
Article in The Journal of nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundVitamin A deficiency (VAD) and obesity are widespread nutrition-related health conditions that are independently associated with pulmonary remodeling processes linked to lung function decline and respiratory diseases.
objectivesThis study tested the hypothesis that VAD-related pulmonary alterations are aggravated by diet-induced obesity.
methodsEight-week-old C57BL/6J/129Sv mice with a deletion of lecithin-retinol-acyltransferase (Lrat-; impaired vitamin A storage) were fed vitamin A deficient control diet (CD, n = 13) or high-fat diet (HFD, n = 15) to induce VAD in lean (CD-VAD, n = 13) or obese (HFD-VAD, n = 13) mice. Wild-type mice receiving vitamin A-containing CD or HFD served as controls. After 20 wk, lungs were subjected to structural and molecular analyses by stereology, western blot, and high-pressure liquid chromatography-mass spectrometry. Statistics used were 2-way analysis of variance.
resultsPulmonary vitamin A reserves were efficiently depleted in CD-VAD and HFD-VAD (P < 0.001 compared with controls). In CD-VAD, 76% of pulmonary elastic fibers appeared densely packed (CD: 53%, P < 0.01), and expression of fibrillin was 110% higher compared with CD (P < 0.01), indicating a higher septal microfibril content. Elastin expression was slightly reduced in HFD-groups (HFD: 14%, HFD-VAD: 16% of respective controls, both P < 0.05), whereas neither diet nor VAD affected expression levels of collagen I or III. Lipid droplet volumes decreased by 32% in septal fibroblasts (P < 0.05) and by 53% in alveolar epithelial type 2 (AE2) cells in CD-VAD, compared with CD. HFD alone led to a 20% reduction in lung airspace volume, a 13% decrease in septal surface area, and a 15% reduction in AE2 cell numbers compared with CD. These VAD- and obesity-related changes were alleviated or absent in HFD-VAD.
conclusionsVAD-induced elastic fiber remodeling and lipid droplet reduction in the alveolar region of lean mice, whereas HFD resulted in smaller lungs containing less AE2 cells. Both VAD- and obesity-related effects were attenuated in HFD-VAD, indicating mutually mitigating effects.
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