Effects of Unfiltered Coffee and Bioactive Coffee Compounds on the Development of Metabolic Syndrome Components in a High-Fat-/High-Fructose-Fed Rat Model.

The literature is inconsistent as to how coffee affects metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. This study aimed to evaluate the effects of unfiltered coffee on diet-induced MetS and investigate whether or not phenolic acids and trigonelline are the main bioactive compounds in coffee. Twenty-four male Sprague‒Dawley rats were fed a high-fat (35% W/W) diet plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water at a dosage equal to 4 cups/day in a human. Compared to the controls, total food intake (p = 0.023) and mean body weight at endpoint (p = 0.016) and estimated average plasma glucose (p = 0.041) were lower only in the coffee group. Surrogate measures of insulin resistance including the overall fasting insulin (p = 0.010), endpoint HOMA-IR (p = 0.022), and oral glucose tolerance (p = 0.029) were improved in the coffee group. Circulating triglyceride levels were lower (p = 0.010), and histopathological and quantitative (p = 0.010) measurements indicated lower grades of liver steatosis compared to controls after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

A Combination of Coffee Compounds Shows Insulin-Sensitizing and Hepatoprotective Effects in a Rat Model of Diet-Induced Metabolic Syndrome.

Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = -0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014) and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-13C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Postoperative but not preoperative treatment with sorafenib inhibits liver regeneration in rats.

BACKGROUND: Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellular carcinoma. The aim of the present study was to investigate the effect of Sorafenib on liver regeneration in healthy rats. METHODS: In two substudies we examined the effect of pre- or post-operative treatment with Sorafenib (15 mg/kg/d). Wistar rats (n = 120) received either Sorafenib (S) or placebo (P). After 70% partial hepatectomy, the rats were euthanized on postoperative days 2, 4, or 8. Body weight and liver weight were recorded and regeneration rate (RR) calculated. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using unbiased stereological methods. RESULTS: Eleven animals (9%) died after surgery. In the preoperative substudy, lower body weight gains during the gavage period in the S group were found. No difference between groups S and P regarding liver weight gain, liver RRs, and hepatocyte proliferation on postoperative days 2 and 4 were found. In the postoperative substudy, significantly lower values of liver weight gain, liver RRs, and hepatocyte proliferation were found in the S group. CONCLUSIONS: In our rat model, Sorafenib did not increase posthepatectomy mortality. Postoperative treatment significantly impaired liver regeneration. Preoperative treatment impaired body weight during the gavage period, but was without effect on liver regeneration.

Manganese superoxide dismutase and breast cancer recurrence: a Danish clinical registry-based case-control study, and a meta-analysis.

BACKGROUND: Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses. METHODS: We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non-metastatic breast cancer from 1990-2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95% confidence intervals (95% CI) of BCR. We used random-effects meta-analytic models to evaluate the association of SOD2 polymorphisms and BCR. RESULTS: The frequency of the SOD2-Ala allele was 70% in cases versus 71% in controls; 40% versus 44% were heterozygotes, and 30% versus 25% were homozygotes, respectively. Heterozygote and homozygote carriers of the Ala allele had no increased rate of BCR (OR = 1.1, 95%CI = 0.65, 2.0, and OR = 0.87, 95%CI = 0.47, 1.6, respectively). Five studies informed the meta-analytic models; summary estimates associating BCR for homozygote, or any inheritance of the variant Ala allele were 1.18 (95%CI = 0.74, 1.88), and 1.18, (95%CI = 0.91, 1.54), respectively. CONCLUSION: Our findings do not suggest that MnSOD enzymatic activity, as measured by SOD2 genotype, affects rates of BCR among patients treated with Cyclo.

Resveratrol up-regulates hepatic uncoupling protein 2 and prevents development of nonalcoholic fatty liver disease in rats fed a high-fat diet.

Obesity is associated with a markedly increased risk of nonalcoholic fatty liver disease. The anti-inflammatory polyphenol resveratrol possess promising properties in preventing this metabolic condition by dampening the pathological inflammatory reaction in the hepatic tissue. However, in the current study, we hypothesize that the beneficial effect of resveratrol is not solely attributable to its anti-inflammatory potential. Eight-week-old male Wistar rats were randomly distributed into 3 groups of 12 animals each: control diet (C), high-fat diet (HF), and HF supplemented with 100 mg resveratrol daily (HFR). After 8 weeks of dietary treatment, the rats were euthanized and relevant tissues were prepared for subsequent analysis. Resveratrol prevented the high fat-induced steatosis assessed by semiquantitative grading, which furthermore corresponded with a complete normalization of the hepatic triglyceride content (P < .001), despite no change in total body fat. In HFR, the hepatic uncoupling protein 2 expression was significantly increased by 76% and 298% as compared with HF and C, respectively. Moreover, the hepatic mitochondria content in HFR was significantly higher as compared with both C and HF (P < .001 and P = .004, respectively). We found no signs of hepatic inflammation, hereby demonstrating that resveratrol protects against fatty liver disease independently of its proposed anti-inflammatory potential. Our data might indicate that an increased number of mitochondria and, particularly, an increase in hepatic uncoupling protein 2 expression are involved in normalizing the hepatic fat content due to resveratrol supplementation in rodents fed a high-fat diet.