Morten Poulsen

High-Dose Resveratrol Supplementation in Obese Men: An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition

Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.

Methylotrophic methanogenic Thermoplasmata implicated in reduced methane emissions from bovine rumen

Rumen methanogens are major sources of anthropogenic methane emissions, and these archaea are targets in strategies aimed at reducing methane emissions. Here we show that the poorly characterised Thermoplasmata archaea in bovine rumen are methylotrophic methanogens and that they are reduced upon dietary supplementation with rapeseed oil in lactating cows. In a metatranscriptomic survey, Thermoplasmata 16S rRNA and methyl-coenzyme M reductase (mcr) transcripts decreased concomitantly with mRNAs of enzymes involved in methanogenesis from methylamines that were among the most abundant archaeal transcripts, indicating that these Thermoplasmata degrade methylamines. Their methylotrophic methanogenic lifestyle was corroborated by in vitro incubations, showing enhanced growth of these organisms upon methylamine supplementation paralleled by elevated methane production. The Thermoplasmata have a high potential as target in future strategies to mitigate methane emissions from ruminant livestock. Our findings and the findings of others also indicate a wider distribution of methanogens than previously anticipated.

Resveratrol in metabolic health: an overview of the current evidence and perspectives

In the search for novel preventive and therapeutic modalities in the management of metabolic diseases and obesity, resveratrol has attracted great attention over the past decades. Preclinical trials suggest that resveratrol mimics the metabolic effects of calorie restriction (CR) via activation of silent mating type information regulation 2 homolog 1 (SIRT1). In experimental animals, this potential translates into prevention or improvement of glucose metabolism, anti‐inflammation, cancer, and nonalcoholic fatty liver disease. Moreover, and in accordance with CR, supplementation with resveratrol promotes longevity in several primitive species and protects against diet‐induced metabolic abnormalities in rodents. Despite the substantial preclinical evidence, human clinical data are very scarce, and even though the compound is widely distributed as an over‐the‐counter human nutritional supplement, its therapeutic rationale has not been well characterized. In this review, we provide a brief overview of the field and discuss the future scientific directions of resveratrol research.

Nitrous oxide emission by aquatic macrofauna

A large variety of aquatic animals was found to emit the potent greenhouse gas nitrous oxide when nitrate was present in the environment. The emission was ascribed to denitrification by ingested bacteria in the anoxic animal gut, and the exceptionally high N2O-to-N2 production ratio suggested delayed induction of the last step of denitrification. Filter- and deposit-feeding animal species showed the highest rates of nitrous oxide emission and predators the lowest, probably reflecting the different amounts of denitrifying bacteria in the diet. We estimate that nitrous oxide emission by aquatic animals is quantitatively important in nitrate-rich aquatic environments like freshwater, coastal marine, and deep-sea ecosystems. The contribution of this source to overall nitrous oxide emission from aquatic environments might further increase because of the projected increase of nitrate availability in tropical regions and the numeric dominance of filter- and deposit-feeders in eutrophic ecosystems.

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.

Mesophilic versus thermophilic anaerobic digestion of cattle manure: methane productivity and microbial ecology

In this study, productivity and physicochemical and microbiological (454 sequencing) parameters, as well as environmental criteria, were investigated in anaerobic reactors to contribute to the ongoing debate about the optimal temperature range for treating animal manure, and expand the general knowledge on the relation between microbiological and physicochemical process indicators. For this purpose, two reactor sizes were used (10 m3 and 16 l), in which two temperature conditions (35°C and 50°C) were tested. In addition, the effect of the hydraulic retention time was evaluated (16 versus 20 days).

Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes

Throughout the Western world obesity prevalence is steadily increasing, and associated metabolic co-morbidities are projected to rise during the years to come. As weight loss and weight maintenance remains a major problem, new strategies to protect against obesity-related morbidity are needed. There is a clear association between obesity, low-grade inflammation and obesity-associated diseases, thus, the development of new anti-inflammatory substances is urgently needed as these may ultimately pave the way for novel treatments of obesity and lifestyle-related diseases. A candidate molecule is the polyphenolic compound resveratrol, and in the present review, we provide an overview of the field, and discuss the future scientific perspectives. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

Methane production and digestion of different physical forms of rapeseed as fat supplements in dairy cows

The purpose of this experiment was to study the effect of the physical form of rapeseed fat on methane (CH4) mitigation properties, feed digestion, and rumen fermentation. Four lactating ruminal-, duodenal-, and ileal-cannulated Danish Holstein dairy cows (143 d in milk, milk yield of 34.3 kg) were submitted to a 4×4 Latin square design with 4 rations: 1 control with rapeseed meal (low-fat, CON) and 3 fat-supplemented rations with either rapeseed cake (RSC), whole cracked rapeseed (WCR), or rapeseed oil (RSO). Dietary fat concentrations were 3.5 in CON, 5.5 in RSC, 6.2 in WCR, and 6.5% in RSO. The amount of fat-free rapeseed was kept constant for all rations. The forage consisted of corn silage and grass silage and the forage to concentrate ratio was 50:50 on a dry matter basis. Diurnal samples of duodenal and ileal digesta and feces were compiled. The methane production was measured for 4 d in open-circuit respiration chambers. Additional fat reduced the CH4 production per kilogram of dry matter intake and as a proportion of the gross energy intake by 11 and 14%, respectively. Neither the total tract nor the rumen digestibility of organic matter (OM) or neutral detergent fiber were significantly affected by the treatment. Relating the CH4 production to the total-tract digested OM showed a tendency to decrease CH4 per kilogram of digested OM for fat-supplemented rations versus CON. The acetate to propionate ratio was not affected for RSC and WCR but was increased for RSO compared with CON. The rumen ammonia concentration was not affected by the ration. The milk and energy-corrected milk yields were unaffected by the fat supplementation. In conclusion, rapeseed is an appropriate fat source to reduce the enteric CH4 production without affecting neutral detergent fiber digestion or milk production. The physical form of fat did not influence the CH4-reducing effect of rapeseed fat. However, differences in the volatile fatty acid pattern indicate that different mechanisms may be involved.

Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4‐month randomised trial in middle‐aged men

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre‐clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size.

Dietary Nitrate for Methane Mitigation Leads to Nitrous Oxide Emissions from Dairy Cows

Nitrate supplements to cattle diets can reduce enteric CH emissions. However, if NO metabolism stimulates NO emissions, the effectiveness of dietary NO for CH mitigation will be reduced. We quantified NO emissions as part of a dairy cow feeding experiment in which urea was substituted in nearly iso-N diets with 0, 5, 14 or 21 g NO kg dry matter (DM). The feeding experiment was a Latin square with repetition of Period 1. Each period lasted 4 wk, with CH emission measurements in Week 4 using respiration chambers. During Period 3, NO concentrations in chamber outlet air were monitored semicontinuously during 48 h. High, but fluctuating, NO concentrations were seen at the two highest NO levels (up to between 2 and 5 μL L), and dynamics were linked with recent feed intake. In Periods 4 and 5, NO concentrations and feed intake were determined from all four respiration chambers during two 7-h periods. Emissions of NO coincided with feed intake, again with NO concentrations in the microliter per liter range at the two highest NO intake levels. Neither feed nor excretion of NO via urine were significant sources of NO, indicating that emissions came from the animals. Leakages due to rumen fistulation could also not account for NO emissions. The possibility that NO is produced in the oral cavity is discussed. Nitrous oxide emission factors ranged between 0.7 and 1.0% except in one case at 21 g NO kg DM, where it was 3.4%. When accounting for NO emissions at the highest NO intake level, the overall GHG mitigation effect in two different animal-diet combinations changed from -47 to -40%, and from -19 to -17%, respectively, due to NO emissions.