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

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2439 ◽  
Author(s):  
Wenbiao Shi ◽  
Maria A. Hegeman ◽  
Atanaska Doncheva ◽  
Melissa Bekkenkamp-Grovenstein ◽  
Vincent C. J. de Boer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dietary Intervention ◽  
Metabolic Health ◽  
Sirtuin 1 ◽  
Metabolic Flexibility ◽  
High Dose ◽  
Gene Markers ◽  
Nicotinamide Riboside ◽  
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.

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

2018 ◽  
Vol 19 (9) ◽  
pp. 2632 ◽  
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.

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

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.

scholarly journals Resveratrol-Induced White Adipose Tissue Browning in Obese Mice by Remodeling Fecal Microbiota

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3356 ◽  
Author(s):  
Weiyao Liao ◽  
Xiaohan Yin ◽  
Qingrong Li ◽  
Hongmin Zhang ◽  
Zihui Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gut Microbiota ◽  
White Adipose Tissue ◽  
Additional Treatment ◽  
The Body ◽  
Sirtuin 1 ◽  
Obese Mice ◽  
Positive Role ◽  
White Fat

Promoting the browning of white fat may be a potential means of combating obesity. Therefore, in this study, we investigated the effect of resveratrol (RES) on the body weight and browning of white fat in high-fat diet (HFD)-induced obese mice and the potential associated mechanism in vivo. Eight-week-old male mice were randomized to receive different treatments: (1), chow without any additional treatment (chow); (2), chow plus 0.4% resveratrol (chow-RES); (3), HFD without any additional treatment (HFD); and (4), HFD plus 0.4% resveratrol (HFD-RES). After 4 weeks of feeding, additional 8-week-old male recipient mice were randomly allocated to the following 4 treatments: (5), HFD and received feces from chow-fed mice; (6), HFD and received feces from chow-RES-fed mice; (7), HFD and received feces from HFD-fed mice; and (8), HFD and received feces from HFD-RES-fed mice. RES treatment significantly inhibited increases in fat accumulation, promoted the browning of white adipose tissue (WAT) and alleviated gut microbiota dysbiosis in HFD-fed mice. Subsequent analyses showed that the gut microbiota remodeling induced by resveratrol had a positive role in WAT browning, and sirtuin-1 (Sirt1) signaling appears to be a key component of this process. Overall, the results show that RES may serve as a potential intervention to reduce obesity by alleviating dysbiosis of the gut microbiota.

scholarly journals Chronic l-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health

2016 ◽  
Vol 93 ◽  
pp. 21-26 ◽  
Author(s):  
Paraskevi Sakellariou ◽  
Angelica Valente ◽  
Andres E. Carrillo ◽  
George S. Metsios ◽  
Liliya Nadolnik ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Health ◽  
Therapeutic Regime

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

2018 ◽  
Vol 62 (21) ◽  
pp. 1800463 ◽  
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

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

Obesity ◽  
2016 ◽  
Vol 25 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Noemí Arias ◽  
Catalina Picó ◽  
M. Teresa Macarulla ◽  
Paula Oliver ◽  
Jonatan Miranda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Obesogenic Diet

scholarly journals Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianfei Lai ◽  
Qianyu Qian ◽  
Qinchao Ding ◽  
Li Zhou ◽  
Ai Fu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Sirtuin 1 ◽  
Male Mice ◽  
High Fat ◽  
Sirt1 Expression ◽  
Salvianolic Acid ◽  
Amp Activated Protein Kinase

Background: Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure.Purpose: The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning.Methods: Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated.Resluts: Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1.Conclusion: Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.

scholarly journals Dynamic of lipid droplets and gene expression in response to β-aminoisobutyric acid treatment on 3T3-L1 cells

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Monica Colitti ◽  
Federico Boschi ◽  
Tommaso Montanari
Keyword(s):  
Adipose Tissue ◽  
Physical Exercise ◽  
Metabolic Health ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Specific Marker ◽  
Rapid Adaptation ◽  
Gene Markers ◽  
Aminoisobutyric Acid ◽  
Beneficial Impact

Research on adipobiology has recognized the browning process of white adipocytes as a potential therapeutic strategy for the treatment of obesity and related morbidities. Physical exercise stimulates the secretion of myokines, such as b-aminoisobutyric acid (BAIBA), which in turn promotes adaptive thermogenesis. White adipocyte conversion to brown cells involves dynamic changes in lipid droplet (LD) dimension and in the transcription of brown-specific marker genes. This study analyzes the effect of different doses of BAIBA and at different days of development on 3T3-L1 cells by evaluating morphological changes in LDs and the expression of browning gene markers. Results suggested that the highest concentration of BAIBA after 4 days of differentiation produced the most significant effects. The number of LDs per cell increased in comparison to control cells, whereas the surface area significantly decreased. Brown adipocyte markers were up-regulated, but the effect of treatment was lost at 10 days of differentiation. The thermogenic program induced by BAIBA may reflect a rapid adaptation of adipose tissue to physical exercise. This connection stresses the beneficial impact of physical exercise on metabolic health. The thermogenic program induced by BAIBA may reflect a rapid adaptation of adipose tissue to physical exercise. This connection stresses the beneficial impact of physical exercise on metabolic health.

Differential Responses of White Adipose Tissue and Brown Adipose Tissue to Calorie Restriction During Aging

2020 ◽  
Author(s):  
Yunlu Sheng ◽  
Fan Xia ◽  
Lei Chen ◽  
Yifan Lv ◽  
Shan Lv ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Disorder ◽  
Energy Homeostasis ◽  
Nutritional Intervention ◽  
Metabolic Health ◽  
Protective Effects ◽  
Age Related ◽  
Brown Adipose

Abstract Age-related adipose tissue dysfunction is potentially important in the development of insulin resistance and metabolic disorder. Caloric restriction (CR) is a robust intervention to reduce adiposity, improve metabolic health, and extend healthy life span. Both white adipose tissue (WAT) and brown adipose tissue (BAT) are involved in energy homeostasis. CR triggers the beiging of WAT in young mice; however, the effects of CR on beiging of WAT and function of BAT during aging are unclear. This study aimed to investigate how age and CR impact the beiging of WAT, the function of BAT, and metabolic health in mice. C57BL/6 mice were fed CR diet (40% less than the ad libitum [AL] diet) for 3 months initiated in young (3 months), middle-aged (12 months), and old (19 months) stage. We found age-related changes in different types of adipose tissue, including adipocyte enlargement, declined beiging of WAT, and declined thermogenic and β-oxidational function of BAT. Moreover, CR attenuated age-associated adipocyte enlargement and prevented the age-related decline in beiging potential of WAT. These protective effects on the beiging potential were significant in inguinal WAT at all three ages, which were significant in epididymal WAT at young and old age. In contrast, thermogenic and β-oxidational function of BAT further declined after CR in the young age group. In conclusion, our findings reveal the contribution of WAT beiging decline to age-related metabolic disorder and suggest nutritional intervention, specifically targeting WAT beiging, as an effective approach to metabolic health during aging.

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