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High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet

Shi, Wenbiao ; Hegeman, Maria A ; Doncheva, Atanaska ; Bekkenkamp-Grovenstein, Melissa ; de Boer, Vincent C J ; Keijer, Jaap

Nutrients, 2019-10, Vol.11 (10), p.2439 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet
Autor: Shi, Wenbiao ; Hegeman, Maria A ; Doncheva, Atanaska ; Bekkenkamp-Grovenstein, Melissa ; de Boer, Vincent C J ; Keijer, Jaap
Assuntos: Adipocytes ; Adipose tissue ; Adipose Tissue, White - drug effects ; Adipose Tissue, White - metabolism ; Animals ; Blood Glucose ; Diabetes ; Diet ; Diet, High-Fat - adverse effects ; Dietary supplements ; Dose-Response Relationship, Drug ; Energy Metabolism - drug effects ; Enzymes ; Gene expression ; Glucose ; Glucose Intolerance ; Glucose tolerance ; Glucose Tolerance Test ; GLUT4 gene ; Homeostasis ; Inflammation - chemically induced ; Insulin ; Insulin resistance ; Intolerance ; Levels ; Male ; Metabolism ; Mice ; nad ; Niacinamide - administration & dosage ; Niacinamide - adverse effects ; Niacinamide - analogs & derivatives ; Niacinamide - pharmacology ; Nicotinamide ; nnt ; Obesity - chemically induced ; Physiological effects ; Physiology ; PPAR gamma ; Proteins ; Supplementation ; vitamin b3
É parte de: Nutrients, 2019-10, Vol.11 (10), p.2439
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Current address: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Current address: Educational Consultancy & Professional Development, Faculty of Social and Behavioral Sciences, Utrecht University, 3508 TC Utrecht, The Netherlands.
Descrição: Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD ) precursor vitamin. The scarce reports on the adverse effects on metabolic health of supplementation with high-dose NR warrant substantiation. Here, we aimed to examine the physiological responses to high-dose NR supplementation in the context of a mildly obesogenic diet and to substantiate this with molecular data. An 18-week dietary intervention was conducted in male C57BL/6JRccHsd mice, in which a diet with 9000 mg NR per kg diet (high NR) was compared to a diet with NR at the recommended vitamin B3 level (control NR). Both diets were mildly obesogenic (40 en% fat). Metabolic flexibility and glucose tolerance were analyzed and immunoblotting, qRT-PCR and histology of epididymal white adipose tissue (eWAT) were performed. Mice fed with high NR showed a reduced metabolic flexibility, a lower glucose clearance rate and aggravated systemic insulin resistance. This was consistent with molecular and morphological changes in eWAT, including sirtuin 1 (SIRT1)-mediated PPARγ (proliferator-activated receptor γ) repression, downregulated AKT/glucose transporter type 4 (GLUT4) signaling, an increased number of crown-like structures and macrophages, and an upregulation of pro-inflammatory gene markers. In conclusion, high-dose NR induces the onset of WAT dysfunction, which may in part explain the deterioration of metabolic health.
Editor: Switzerland: MDPI AG
Idioma: Inglês;Norueguês

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High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet

Shi, Wenbiao ; Hegeman, Maria A ; Doncheva, Atanaska ; Bekkenkamp-Grovenstein, Melissa ; de Boer, Vincent C J ; Keijer, Jaap

Switzerland: MDPI AG

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