Dietary Supplementation with Galactooligosaccharides Attenuates High-Fat, High-Cholesterol Diet-Induced Glucose Intolerance and Disruption of Colonic Mucin Layer in C57BL/6 Mice and Reduces Atherosclerosis in Ldlr-/- Mice.
J Nutr
; 150(2): 285-293, 2020 02 01.
Article
em En
| MEDLINE
| ID: mdl-31586202
ABSTRACT
BACKGROUND:
A Western-type diet (WD), rich in fat and cholesterol but deficient in fiber, induces development of diabetes and atherosclerosis. Colonic bacteria use the gut's mucous lining as an alternate energy source during periods of fiber deficiency, resulting in intestinal barrier erosion.OBJECTIVE:
We hypothesized that supplementing a WD with galactooligosaccharide (GOS) fiber would attenuate WD-induced mucin layer disruption and attenuate development of metabolic diseases.METHODS:
C57BL/6 mice (both sexes, 8-10 wk of age) were fed a standard rodent diet (TD7012, reference) or a high-fat, high-cholesterol-containing WD (TD88137, 21% fat, 0.15% cholesterol, 19.5% caesin) or a WD supplemented with 5% GOS fiber (TD170432, WD + GOS) for 16 wk. WD-fed mice that were gavaged daily with curcumin (100 mg/kg) served as positive controls. Glucose tolerance, colonic mucin layer, gene expression, and circulating macrophage/neutrophil levels were determined. Hyperlipidemic Ldlr-/- mice (both sexes, 8-10 wk of age) fed a WD with or without GOS supplementation (for 16 wk) were used to assess plasma LPS and atherosclerosis. Effects of dietary supplementation on different parameters were compared for each genotype.RESULTS:
Compared with a WD, glucose tolerance was significantly improved in male C57BL/6 mice fed a WD + GOS (mean ± SEM AUC = 53.6 ± 43.9 compared with 45.4 ± 33.3 g â min/dL; P = 0.015). Continuity of colonic mucin layer (MUC-2 expression) was improved in mice receiving GOS supplementation, indicating improved intestinal barrier. GOS supplementation also reduced circulating macrophages (30% decrease) and neutrophils (60% decrease), suggesting diminished systemic inflammation. In Ldlr-/- mice, GOS supplementation significantly reduced plasma LPS concentrations (mean ± SEM 0.81 ± 0.43 EU/mL compared with 0.32 ± 0.26 EU/mL, P < 0.0001, in females and 0.56 ± 0.24 EU/mL compared with 0.34 ± 0.12 EU/mL, P = 0.036, in males), improved glucose tolerance in male mice, and attenuated atherosclerotic lesion area (mean ± SEM 54.2% ± 6.19% compared with 43.0% ± 35.12%, P = 0.0006, in females and 54.6% ± 3.99% compared with 43.1% ± 8.11%, P = 0.003, in males).CONCLUSIONS:
GOS fiber supplementation improves intestinal barrier in C57BL/6 and Ldlr-/- mice and significantly attenuates WD-induced metabolic diseases and, therefore, may represent a novel strategy for management of these diseases.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oligossacarídeos
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Receptores de LDL
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Colesterol na Dieta
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Suplementos Nutricionais
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Aterosclerose
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Dieta Hiperlipídica
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Galactose
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Teste de Tolerância a Glucose
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Mucosa Intestinal
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Mucinas
Limite:
Animals
Idioma:
En
Revista:
J Nutr
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos