Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet

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.

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Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity

10.1101/834416 ◽

2019 ◽

Author(s):

Lidewij Schipper ◽

Steffen van Heijningen ◽

Giorgio Karapetsas ◽

Eline M. van der Beek ◽

Gertjan van Dijk

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Intake ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Tissue Mass ◽

Individual Housing ◽

Adipose Tissue Mass ◽

Obesogenic Diet

AbstractIndividual housing from weaning onwards resulted in reduced growth rate during adolescence in male C57Bl/6J mice that were housed individually, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice. Body weight gain of individually housed animals exceeded that of socially housed mice during adulthood, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition. This study shows that post-weaning individual housing of male mice results in impaired adolescent growth and higher susceptibility to obesity in adulthood. Mice are widely used to study obesity and cardiometabolic comorbidities. For (metabolic) research models using mice, (social) housing practices should be carefully considered and regarded as a potential confounder due to their modulating effect on metabolic health outcomes.

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Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201800463 ◽

2018 ◽

Vol 62 (21) ◽

pp. 1800463 ◽

Cited By ~ 10

Author(s):

Alba Serrano ◽

Madhu Asnani-Kishnani ◽

Ana María Rodríguez ◽

Andreu Palou ◽

Joan Ribot ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Postnatal Life ◽

Nicotinamide Riboside ◽

Adult Mice ◽

Early Postnatal Life

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A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet

Obesity ◽

10.1002/oby.21706 ◽

2016 ◽

Vol 25 (1) ◽

pp. 111-121 ◽

Cited By ~ 38

Author(s):

Noemí Arias ◽

Catalina Picó ◽

M. Teresa Macarulla ◽

Paula Oliver ◽

Jonatan Miranda ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Obesogenic Diet

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AdipoAtlas: A Reference Lipidome for Human White Adipose Tissue

10.1101/2021.01.20.427444 ◽

2021 ◽

Author(s):

Mike Lange ◽

Georgia Angelidou ◽

Zhixu Ni ◽

Angela Criscuolo ◽

Jürgen Schiller ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Metabolic Disorders ◽

Prognostic Markers ◽

Absolute Quantification ◽

Accurate Identification ◽

Disease Etiology ◽

Metabolic Dysregulation ◽

Lipid Molecular Species ◽

Wide Range

SummaryObesity, characterized by expansion and metabolic dysregulation of white adipose tissue (WAT), has reached pandemic proportions and acts as a primer for a wide range of metabolic disorders. Remodelling of WAT lipidome in obesity and associated comorbidities can explain disease etiology and provide valuable diagnostic and prognostic markers. To support understanding of WAT lipidome remodelling at the molecular level, we performed in-depth lipidomics profiling of human subcutaneous and visceral WAT of lean and obese individuals. Tissue-tailored preanalytical and analytical workflows allowed accurate identification and semi-absolute quantification of 1636 and 737 lipid molecular species, respectively, and summarized here in a form of human WAT reference lipidome. Deep lipidomic profiling allowed to identify main lipid (sub)classes undergoing depot/phenotype specific remodelling. Furthermore, previously unanticipated diversity of WAT ceramides was uncovered. AdipoAtlas reference lipidome will serve as a data-rich resource for the development of WAT-specific high-throughput methods and as a scaffold for systems medicine data integration.

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Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00520.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. R816-R820 ◽

Cited By ~ 16

Author(s):

Jaycob D. Warfel ◽

Bolormaa Vandanmagsar ◽

Olga S. Dubuisson ◽

Sydney M. Hodgeson ◽

Carrie M. Elks ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Human Subjects ◽

Carnitine Palmitoyltransferase ◽

Whole Body ◽

Acid Oxidation ◽

Moderate Amount ◽

Wide Range ◽

Obesity In Mice ◽

Carnitine Palmitoyltransferase 1

Carnitine palmitoyltransferase 1 (CPT1) is essential for the transport of long-chain fatty acids into the mitochondria for oxidation. Recently, it was reported that decreased CPT1b mRNA in adipose tissue was a contributing factor for obesity in rats. We therefore closely examined the expression level of Cpt1 in adipose tissue from mice, rats, and humans. Cpt1a is the predominate isoform in adipose tissue from all three species. Rat white adipose tissue has a moderate amount of Cpt1b mRNA, but it is very minor compared with Cpt1b expression in muscle. Total CPT1 activity in adipose tissue is also minor relative to other tissues. Both Cpt1a and Cpt1b mRNA were increased in gonadal fat but not inguinal fat by diet-induced obesity in mice. We also measured CPT1a and CPT1b expression in subcutaneous adipose tissue from human subjects with a wide range of body mass indexes (BMIs). Interestingly, CPT1a expression positively correlated with BMI ( R = 0.46), but there was no correlation with CPT1b ( R = 0.04). Our findings indicate that white adipose tissue fatty acid oxidation capacity is minor compared with that of metabolically active tissues. Furthermore, given the already low abundance of Cpt1b in white adipose tissue, it is unlikely that decreases in its expression can quantitatively decrease whole body energy expenditure enough to contribute to an obese phenotype.

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Stanniocalcin-1 and -2 effects on glucose and lipid metabolism in white adipose tissue from fed and fasted rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0023 ◽

2019 ◽

Vol 97 (10) ◽

pp. 916-923 ◽

Cited By ~ 6

Author(s):

Elaine Sarapio ◽

Samir K. De Souza ◽

Jorge F.A. Model ◽

Marcia Trapp ◽

Roselis S.M. Da Silva

Keyword(s):

Adipose Tissue ◽

Glucose Metabolism ◽

Glucose Uptake ◽

White Adipose Tissue ◽

Mammalian Cells ◽

Acid Synthesis ◽

Direct Role ◽

Glucose And Lipid Metabolism ◽

Triacylglycerol Synthesis ◽

Wide Range

Stanniocalcin-1 and -2 belong to a family of molecules that exhibit both paracrine and autocrine effects in mammalian cells. Human stanniocalcin-1 (hSTC-1) is expressed in a wide range of tissues, including white adipose tissue. In fed rats, hSTC-1 increases carbon flux from glucose to lipids in retroperitoneal white adipose tissue. Human stanniocalcin-2 (hSTC-2) is expressed in almost all tissues and regulates various biological processes. The aim of this work was to study the action of hSTC-1 and hSTC-2 in the lipid and glucose metabolism of epididymal white adipose tissue (eWAT) in rats in different nutritional states. This study shows for the first time an opposite effect of hSTC-1 and hSTC-2 on glyceride-glycerol generation from glucose in eWAT of fed rats. hSTC-1 stimulated the storage of triacylglycerol in eWAT in the postprandial period, increasing glucose uptake and glyceride-glycerol generation from 14C-glucose. hSTC-2 decreased triacylglycerol synthesis, reducing glyceride-glycerol generation from 14C-glucose, direct phosphorylation of glycerol, and fatty acid synthesis from 14C-glucose in eWAT of fed rats. However, both hormones increased glucose uptake in fed and fasting states. These findings provide evidence for a direct role of hSTC-1 and hSTC-2 in the regulation of lipid and glucose metabolism in eWAT of rats.

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Chickens from lines selected for high and low body weight show differences in fatty acid oxidation efficiency and metabolic flexibility in skeletal muscle and white adipose tissue

International Journal of Obesity ◽

10.1038/ijo.2014.8 ◽

2014 ◽

Vol 38 (10) ◽

pp. 1374-1382 ◽

Cited By ~ 21

Author(s):

S Zhang ◽

R P McMillan ◽

M W Hulver ◽

P B Siegel ◽

L H Sumners ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Adipose Tissue ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

White Adipose Tissue ◽

Acid Oxidation ◽

Metabolic Flexibility ◽

Oxidation Efficiency

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Grape Seed Proanthocyanidins Improve White Adipose Tissue Expansion during Diet-Induced Obesity Development in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms19092632 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2632 ◽

Cited By ~ 5

Author(s):

Aïda Pascual-Serrano ◽

Cinta Bladé ◽

Manuel Suárez ◽

Anna Arola-Arnal

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Grape Seed ◽

Sirtuin 1 ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Adipocyte Size ◽

Metabolic Complications ◽

Peroxisome Proliferator Activated Receptor ◽

Obesogenic Diet

The development of metabolic complications associated with obesity has been correlated with a failure of white adipose tissue (WAT) to expand. Our group has previously reported that a 12-week administration of grape seed proanthocyanidin extract (GSPE) together with an obesogenic diet mitigated the development of cardiometabolic complications in rats. Using the same cohort of animals, we aim to elucidate whether the prevention of cardiometabolic complications by proanthocyanidins is produced by a healthier expansion of visceral WAT and/or an induction of the browning of WAT. For this, adipocyte size and number in retroperitoneal WAT (rWAT) were determined by histological analyses, and the gene expression levels of markers of adipogenesis, browning, and WAT functionality were quantified by RT-qPCR. The long-term administration of GSPE together with an obesogenic diet expanded rWAT via an increase in the adipocyte number and a preventive decrease in the adipocyte size in a dose-dependent manner. At the molecular level, GSPE seems to induce WAT adipogenesis through the upregulation of peroxisome proliferator-activated receptor (Pparγ) in a Sirtuin 1 (Sirt1)-dependent manner. In conclusion, the healthier visceral WAT expansion induced by proanthocyanidins supplementation may explain the improvement in the cardiometabolic risks associated with obesogenic diets.

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DNA Methylation Changes are Associated with the Programming of White Adipose Tissue Browning Features by Resveratrol and Nicotinamide Riboside Neonatal Supplementations in Mice

Nutrients ◽

10.3390/nu12020461 ◽

2020 ◽

Vol 12 (2) ◽

pp. 461

Author(s):

Alba Serrano ◽

Madhu Asnani-Kishnani ◽

Charlene Couturier ◽

Julien Astier ◽

Andreu Palou ◽

...

Keyword(s):

Dna Methylation ◽

Adipose Tissue ◽

White Adipose Tissue ◽

De Novo ◽

Brown Adipocyte ◽

Chow Diet ◽

Male Mice ◽

Nicotinamide Riboside ◽

Epigenetic Effects

Neonatal supplementation with resveratrol (RSV) or nicotinamide riboside (NR) programs in male mice brown adipocyte-like features in white adipose tissue (WAT browning) together with improved metabolism in adulthood. We tested the involvement in this programming of long-term epigenetic changes in two browning-related genes that are overexpressed in WAT of supplemented mice, Slc27a1 and Prdm16. Suckling mice received orally the vehicle, RSV or NR from postnatal days 2-to-20. After weaning (d21) onto a chow diet, male mice were habituated to a normal-fat diet (NFD) starting d75, and split on d90 into continuation on the NFD or switching to a high-fat diet (HFD) until euthanization on d164. CpG methylation by bisulfite-sequencing was analyzed on inguinal WAT. Both treatments modified methylation marks in Slc27a1 and Prdm16 and the HFD-dependent dynamics of these marks in the adult WAT, with distinct and common effects. The treatments also affected gene expression of de novo DNA methylases in WAT of young animals (euthanized at d35 in independent experiments). Studies in 3T3-L1 adipocytes indicated the direct effects of RSV and NR on the DNA methylation machinery and favoring browning features. The results support epigenetic effects being involved in WAT programming by neonatal RSV or NR supplementation in male mice.

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