Lack of Tissue Accumulation of Grape Seed Flavanols after Daily Long-Term Administration in Healthy and Cafeteria-Diet Obese Rats

Margalef, María; Pons, Zara; Iglesias‐Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña

doi:10.1021/acs.jafc.5b03856

Cited by 24 publications

(18 citation statements)

References 53 publications

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“…This may, in part, be due to altered polyphenolic transport and metabolism in the liver and colon . Concentrations of parent compounds and their metabolites in adipose tissue of obese rats were reported to be lower than in lean rats . In an acute (one‐day) human clinical study, plasma and urine metabolites of blackberry polyphenols were lower in overweight/obese compared to lean individuals .…”

Section: Discussionmentioning

confidence: 99%

“…[46] Concentrations of parent compounds and their metabolites in adipose tissue of obese rats were reported to be lower than in lean rats. [47] In an acute (oneday) human clinical study, plasma and urine metabolites of black-berry polyphenols were lower in overweight/obese compared to lean individuals. [48] In contrast, in this study with mango gallotannins, there were no significant differences between lean and obese individuals at baseline.…”

Section: Bmi As a Determinant Of Gallotannin Pharmacokineticsmentioning

confidence: 99%

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Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals

Barnes

Kim

Fang

et al. 2018

Molecular Nutrition Food Res

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Scope This human clinical pilot trial investigated pharmacokinetics of gallotannin‐metabolites and modulation of intestinal microbiota in healthy lean and obese individuals after 6 weeks of daily mango consumption. Methods and results Participants are divided into three groups: Lean Mango (LM: n = 12; BMI = 22.9 kg m−2), Obese Mango (OM: n = 9; BMI = 34.6 kg m−2), and Lean Control (LC: n = 11; BMI = 22.1 kg m−2). LM and OM consumed 400 g of mango per day for 6 weeks. LC consumed mango only on Days 0 and 42. After 6 weeks, LM experienced increased systemic exposure (AUC0–8h) to gallotannin‐metabolites, 1.4‐fold (p = 0.043). The greatest increase is 4‐O‐methyl‐gallic acid, 3.3‐fold (p = 0.0026). Cumulative urinary excretion of gallotannin‐metabolites significantly increased in LM and OM, but not LC. For OM, qPCR data show increased levels of tannase‐producing Lactococcus lactis and decreased levels of Clostridium leptum and Bacteroides thetaiotaomicron, bacteria associated with obesity. LM experienced an increased trend of fecal levels of butyric (1.3‐fold; p = 0.09) and valeric acids (1.5‐fold; p = 0.056). Plasma endotoxins showed a decreased trend in LM and OM. Conclusion Continuous mango intake significantly increased systemic exposure to gallotannin‐ metabolites and induced an increased trend for fecal short‐chain fatty acids in lean but not obese individuals. This pharmacokinetic discrepancy may result in BMI‐associated reduced gallotannin‐derived health benefits.

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Section: Discussionmentioning

confidence: 99%

Section: Bmi As a Determinant Of Gallotannin Pharmacokineticsmentioning

confidence: 99%

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals

Barnes

Kim

Fang

et al. 2018

Molecular Nutrition Food Res

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“…GSPE was kindly provided by Les Dérives Résiniques et Terpéniques (Dax, France). The composition of the GSPE was previously characterized by Margalef et al 16 and is described in Supplementary Table 1 . Gallic acid (98.5% purity) was purchased from Sigma-Aldrich (G7384, Madrid, Spain).…”

Section: Methodsmentioning

confidence: 99%

Grape seed proanthocyanidin supplementation reduces adipocyte size and increases adipocyte number in obese rats

et al. 2017

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A Pascual-Serrano, A Arola-Arnal, S Suárez-García, FI Bravo, M Suárez, L Arola and C Bladé OBJECTIVES: White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT. DESIGN: Male Wistar rats were fed a standard chow diet (n = 6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25 mg GSPE/kg body weight (n = 6), 7 mg gallic acid/kg body weight (n = 6) or the vehicle (n = 6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR. RESULTS: GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPARƴ tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT. CONCLUSIONS: GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier expansion of WAT to match the surplus energy provided by the cafeteria diet.

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“…However, previous studies with a lower dose (100 mg GSPE/kg bw) administered for a longer time (12 weeks) suggested that flavonoids do not accumulate in liver or mesenteric adipose tissue. 36 Another explanation might be that some epigenetic activity is taking place in the target tissues. GSPE modified liver miR-33a and miR-122 37 at doses as low as 5 mg/kg BW for 3 weeks after a 15-week cafeteria diet.…”

Section: Discussionmentioning

confidence: 99%

Long-lasting effects of proanthocyanidins in rat prevent cafeteria diet effects by limiting adipose tissue accrual

Ginés

Gil-Cardoso

Serrano

et al. 2019

Preprint

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23A dose of proanthocyanidins with satiating properties proved to be able to limit body 24 weight increase several weeks after administration under exposure to a cafeteria diet. Here 25 we describe the molecular targets and the duration of the effects. We treated rats with 500 26 mg GSPE/kg BW for ten days. Seven or seventeen weeks after the last GSPE dose, while 27 animals were on cafeteria diet, we used RT-PCR to measure the mRNA of the key energy 28 metabolism enzymes from liver, adipose depots and muscle. We found that a reduction in 29 the expression of adipose Lpl might explain the lower amount of adipose tissue in rats 30 seven weeks after the last GSPE dose. Liver showed increased expression of Cpt1a and 31 Hmgs2 together with a reduction in Fasn and Dgat2. In addition, fatty oxidation (Oxct1 and 32 Cpt1b mRNA) was increased in muscle. However, after seventeen weeks, there was a 33 completely different gene expression pattern. As conclusion, seven weeks after the last 34 GSPE administration there was a limitation in adipose accrual that might be mediated by 35 an inhibition of the gene expression of the adipose tissue Lpl. Concomitantly there was an 36 increase in fatty acid oxidation in liver and muscle. 37

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Lack of Tissue Accumulation of Grape Seed Flavanols after Daily Long-Term Administration in Healthy and Cafeteria-Diet Obese Rats

Cited by 24 publications

References 53 publications

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals

Grape seed proanthocyanidin supplementation reduces adipocyte size and increases adipocyte number in obese rats

Long-lasting effects of proanthocyanidins in rat prevent cafeteria diet effects by limiting adipose tissue accrual

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