Cranberry polyphenols and agave agavins impact gut immune response and microbiota composition while improving gut barrier function, inflammation, and glucose metabolism in mice fed an obesogenic diet.

The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of Akkermansia muciniphila, a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria Muribaculum intestinale, Faecalibaculum rodentium, Bacteroides uniformis, and Bacteroides acidifaciens. This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 (Tlr2) expression, while decreasing the expression of interleukin 1ß (ILß1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker Foxp3, while CP increased the expression of NOD-like receptor family pyrin domain containing 6 (Nlrp6) inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis.

Marginal Impact of Brown Seaweed Ascophyllum nodosum and Fucus vesiculosus Extract on Metabolic and Inflammatory Response in Overweight and Obese Prediabetic Subjects.

The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.

Salmon peptides limit obesity-associated metabolic disorders by modulating a gut-liver axis in vitamin D-deficient mice.

OBJECTIVE: This study investigated the effects of a low-dose salmon peptide fraction (SPF) and vitamin D3 (VitD3 ) in obese and VitD3 -deficient mice at risk of metabolic syndrome (MetS). METHODS: Obese and VitD3 -deficient low-density lipoprotein receptor (LDLr)-/- /apolipoprotein B100 (ApoB)100/100 mice were treated with high-fat high-sucrose diets, with 25% of dietary proteins replaced by SPF or a nonfish protein mix (MP). The SPF and MP groups received a VitD3 -deficient diet or a supplementation of 15,000 IU of VitD3 per kilogram of diet. Glucose homeostasis, atherosclerosis, nonalcoholic fatty liver disease, and gut health were assessed. RESULTS: VitD3 supplementation increased plasma 25-hydroxyvitamin D to optimal status whereas the VitD3 -deficient diet maintained moderate deficiency. SPF-treated groups spent more energy and accumulated less visceral fat in association with an improved adipokine profile. SPF lowered homeostatic model assessment of insulin resistance compared with MP, suggesting that SPF can improve insulin sensitivity. SPF alone blunted hepatic and colonic inflammation, whereas VitD3 supplementation attenuated ileal inflammation. These effects were associated with changes in gut microbiota such as increased Mogibacterium and Muribaculaceae. CONCLUSIONS: SPF treatment improves MetS by modulating hepatic and gut inflammation along with gut microbiota, suggesting that SPF operates through a gut-liver axis. VitD3 supplementation has limited influence on MetS in this model.

Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice.

BACKGROUND: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.

Characterization of a Coproduct from the Sea Cucumber Cucumaria frondosa and Its Effects on Visceral Adipocyte Size in Male Wistar Rats.

Sea cucumbers have been shown to have potential health benefits and are a rich source of several bioactive compounds, particularly triterpenoid saponins. However, most studies concentrate on the body wall, and little is known about the health effects of the coproducts. The objectives of this study were to determine the nutritional composition of a coproduct from the sea cucumber Cucumaria frondosa and the effects of the dietary consumption of this coproduct on cardiometabolic health in rats. Chemical, biochemical, and nutritional analyses were performed to characterize this coproduct. Forty (40) male Wistar rats were then equally divided into four groups and fed a purified control diet or a diet enriched with 0.5%, 1.5%, or 2.5% (by protein) of coproduct. After 28 days of feeding, the rats were sacrificed. Body and tissue weight, body composition, epididymal adipocyte diameter, plasma and hepatic lipids, glycemia, and insulinemia were measured at the end of the 28-day experiment. Analysis of the coproduct revealed high levels of protein, omega-3 fatty acids, minerals, and saponins. The 1.5% group had significantly smaller epididymal adipocytes vs. the control. We conclude that dietary administration of this sea cucumber coproduct at 1.5% doses decreases visceral adiposity, potentially decreasing the risk of cardiometabolic dysfunction. The coproduct's saponin content may contribute to the observed effects, but the impact of other components cannot be ruled out.

Maternal folic acid supplementation does not counteract the deleterious impact of prenatal exposure to environmental pollutants on lipid homeostasis in male rat descendants.

Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father's transmission of environmental effects in addition to mother's can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/- FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.

Acute Effects of Single Doses of Bonito Fish Peptides and Vitamin D on Whole Blood Gene Expression Levels: A Randomized Controlled Trial.

Fish contains high quality proteins and essential nutrients including 25-hydroxyvitamin D (25(OH)D). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between 25(OH)D deficiency, CVD and CVD risk factors, such as diabetes. This study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was performed. Differences in whole-genome expression levels after versus before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3 + BPH treatments, respectively. VitD3-containing treatments affected the expression of the solute carrier family 25 member 20 (SLC25A20) gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.

Seafood intake and the development of obesity, insulin resistance and type 2 diabetes.

We provide an overview of studies on seafood intake in relation to obesity, insulin resistance and type 2 diabetes. Overweight and obesity development is for most individuals the result of years of positive energy balance. Evidence from intervention trials and animal studies suggests that frequent intake of lean seafood, as compared with intake of terrestrial meats, reduces energy intake by 4-9 %, sufficient to prevent a positive energy balance and obesity. At equal energy intake, lean seafood reduces fasting and postprandial risk markers of insulin resistance, and improves insulin sensitivity in insulin-resistant adults. Energy restriction combined with intake of lean and fatty seafood seems to increase weight loss. Marine n-3 PUFA are probably of importance through n-3 PUFA-derived lipid mediators such as endocannabinoids and oxylipins, but other constituents of seafood such as the fish protein per se, trace elements or vitamins also seem to play a largely neglected role. A high intake of fatty seafood increases circulating levels of the insulin-sensitising hormone adiponectin. As compared with a high meat intake, high intake of seafood has been reported to reduce plasma levels of the hepatic acute-phase protein C-reactive protein level in some, but not all studies. More studies are needed to confirm the dietary effects on energy intake, obesity and insulin resistance. Future studies should be designed to elucidate the potential contribution of trace elements, vitamins and undesirables present in seafood, and we argue that stratification into responders and non-responders in randomised controlled trials may improve the understanding of health effects from intake of seafood.

The Effect of Lean-Seafood and Non-Seafood Diets on Fecal Metabolites and Gut Microbiome: Results from a Randomized Crossover Intervention Study.

SCOPE: The impact of dietary protein types on the gut microbiome is scarcely studied. The aim of the present study is therefore to examine the effects of lean-seafood and non-seafood proteins on the gut microbiome composition and activity and elucidate potential associations to cardiovascular disease (CVD) risk factors. METHODS: A crossover intervention study in which 20 healthy subjects consumed two diets that varied in protein source was conducted. 1 H NMR spectroscopy and 16S rDNA sequencing analyses were applied to characterize fecal metabolites and gut microbiota composition, respectively. RESULTS: A twofold increase in fecal trimethylamine excretion was observed after the lean-seafood diet period. Circulating TAG and the total to high-density lipoprotein (HDL) cholesterol ratio as well as circulating TMAO levels were each associated with specific gut bacteria. Following the non-seafood diet period, a decreased relative abundance of Clostridium cluster IV and a tendency toward an increased Firmicutes/Bacteroidetes ratio were found. CONCLUSIONS: Lean-seafood and non-seafood diets differentially modulate the gut microbiome composition and activity. Furthermore, the gut microbiota composition seems to affect circulating TMAO levels and CVD risk factors.

Liver and plasma lipid changes induced by cyclic fatty acid monomers from heated vegetable oil in the rat.

Cyclic fatty acid monomers (CFAM) generated through domestic or industrial heating of vegetable oils may alter liver enzymes and induce hepatomegaly and steatosis, but the underlying mechanisms are not clearly understood. This study aimed to assess the effects of CFAM on liver and plasma lipids and to determine whether these effects are modulated by dietary lipids. Thirty-six (36) male Wistar rats were fed either of the four isoenergetic diets consisting of canola oil or soybean oil with/without 500 mg/100 g CFAM of total fat for 28 days. Rats fed CFAM had higher liver total lipids (p = 0.03) and triacylglycerols (TAG) (p = 0.02), but less hepatic phosphatidylcholine (p = 0.02) compared to those fed the non-CFAM diets. CFAM did not alter liver phosphatidylethanolamine N-methyltransferase (PEMT) activity and CTP: phosphocholine cytidylyltransferase (CT-α) protein levels. Rats fed CFAM diets had higher levels of plasma total cholesterol (TC), VLDL + LDL cholesterol, higher ratio of TC to HDL cholesterol, and lower levels of HDL cholesterol compared with rats fed non-CFAM diets (p < 0.05). Plasma alanine transaminase (ALT) was decreased with CFAM, but plasma insulin, glucose, and TAG did not vary among the four diet groups (p < 0.05). Rats fed canola oil and CFAM had higher plasma levels of aspartate transaminase (AST) and AST/ALT ratio compared with the other three diet groups. These results indicate that CFAM may provoke an accumulation of TAG in the liver related to a decrease in phosphatidylcholine (PC) levels, but the effect of CFAM on PC concentrations may not occur through impairment of the two main PC biosynthesis pathways.

Mediator, known as a coactivator, can act in transcription initiation in an activator-independent manner in vivo.

Mediator is an evolutionarily conserved complex best known for its role as a coactivator responsible for transducing regulatory signals from DNA-bound activators to the basal RNA polymerase II (Pol II) machinery that initiates transcription from promoters of protein-encoding genes. By exploiting our in vivo activator-independent transcription assay in Saccharomyces cerevisiae, in combination with new temperature sensitive (ts) mutants of Med14 N-terminal half exhibiting widespread transcriptional defects, and existing ts mutants of Kin28 and Med17, we show that, in the absence of activator: (i) Mediator can associate with a promoter as a form devoid of the Cyclin-dependent kinase 8 (CDK8) module, and this association remains regulated by Kin28; (ii) Mediator can stimulate the assembly of the entire Pol II initiation machinery. Although the literature emphasizes the role of the interaction between activators and Mediator, together our results support the view that Mediator is able to act through a dual mechanism in vivo, activator-dependent but also activator-independent, therefore not always as a coactivator.

Effects of Cyclic Fatty Acid Monomers from Heated Vegetable Oil on Markers of Inflammation and Oxidative Stress in Male Wistar Rats.

This study assesses the effects of cyclic fatty acid monomers (CFAM) from heated vegetable oils on oxidative stress and inflammation. Wistar rats were fed either of these four diets for 28 days: canola oil (CO), canola oil and 0.5% CFAM (CC), soybean oil (SO), and soybean oil and 0.5% CFAM (SC). Markers of oxidative stress and inflammation were determined by micro liquid chromatography tandem mass spectrometry (micro-LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) kits, respectively. Analysis of variance (ANOVA) for a 2 × 2 factorial design was performed to determine the CFAM and oil effects and interactions between these two factors at P ≤ 0.05. For significant interactions, a post hoc multiple comparison test was performed, i.e., Tukey HSD (honest significant difference) test. CFAM induced higher plasma levels of 15-F2t-IsoP (CC, 396 ± 43 ng/mL, SC, 465 ± 75 ng/mL vs CO, 261 ± 23 ng/mL and SO, 288 ± 35 ng/mL, P < 0.05). Rats fed the SC diet had higher plasma 2,3-dinor-15-F2t-IsoP (SC, 145 ± 9 ng/mL vs CC, 84 ± 8 ng/mL, CO, 12 ± 1 ng/mL, and SO, 12 ± 1 ng/mL, P < 0.05), urinary 2,3-dinor-15-F2t-IsoP (SC, 117 ± 12 ng/mL vs CC, 67 ± 13 ng/mL, CO, 15 ± 2 ng/mL, and SO, 18 ± 4 ng/mL, P < 0.05), and plasma IL-6 (SC, 57 ± 10 pg/mL vs CC, 48 ± 11 pg/mL, CO, 46 ± 9 pg/mL, and SO, 44 ± 4 pg/mL, P < 0.05) than the other three diet groups. These results indicate that CFAM increased the levels of markers of oxidative stress, and those effects are exacerbated by a CFAM-high-linoleic acid diet.

The Effect of Lean-Seafood and Non-Seafood Diets on Fasting and Postprandial Serum Metabolites and Lipid Species: Results from a Randomized Crossover Intervention Study in Healthy Adults.

The metabolic effects associated with intake of different dietary protein sources are not well characterized. We aimed to elucidate how two diets that varied in main protein sources affected the fasting and postprandial serum metabolites and lipid species. In a randomized controlled trial with crossover design, healthy adults (n = 20) underwent a 4-week intervention with two balanced diets that varied mainly in protein source (lean-seafood versus non-seafood proteins). Nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry analyses were applied to examine the effects of the two diets on serum metabolites. In the fasting state, the lean-seafood diet period, as opposed to the non-seafood diet period, significantly decreased the serum levels of isoleucine and valine, and during the postprandial state, a decreased level of lactate and increased levels of citrate and trimethylamine N-oxide were observed. The non-seafood diet significantly increased the fasting level of 26 lipid species including ceramides 18:1/14:0 and 18:1/23:0 and lysophosphatidylcholines 20:4 and 22:5, as compared to the lean-seafood diet. Thus, the lean-seafood diet decreased circulating isoleucine and valine levels, whereas the non-seafood diet elevated the levels of certain ceramides, metabolites that are associated with insulin-resistance.

Selenium-regulated hierarchy of human selenoproteome in cancerous and immortalized cells lines.

BACKGROUND: Selenoproteins (25 genes in human) co-translationally incorporate selenocysteine using a UGA codon, normally used as a stop signal. The human selenoproteome is primarily regulated by selenium bioavailability with a tissue-specific hierarchy. METHODS: We investigated the hierarchy of selenoprotein expression in response to selenium concentration variation in four cell lines originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno-detection, (iv) selenium-specific mass spectrometric detection after non-radioactive 76Se labeling of selenoproteins, and (v) luciferase-based reporter constructs in various cell extracts. RESULTS: We characterized cell-line specific alterations of the selenoproteome in response to selenium variation that, in most of the cases, resulted from a translational control of gene expression. We established that UGA-selenocysteine recoding efficiency, which depends on the nature of the SECIS element, dictates the response to selenium variation. CONCLUSIONS: We characterized that selenoprotein hierarchy is cell-line specific with conserved features. This analysis should be done prior to any experiments in a novel cell line. GENERAL SIGNIFICANCE: We reported a strategy based on complementary methods to evaluate selenoproteome regulation in human cells in culture.

Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: a parallel, double-blind, controlled and randomised clinical trial.

Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

Shrimp Protein Hydrolysate Modulates the Timing of Proinflammatory Macrophages in Bupivacaine-Injured Skeletal Muscles in Rats.

This study was designed to determine whether marine-derived proteins other than cod could have beneficial effects on inflammation following muscle injury. Macrophage and neutrophil densities were measured from bupivacaine-injured tibialis anterior muscle of rats fed isoenergetic diets containing either shrimp hydrolysate (Shr), casein hydrolysate (CaH), or whole casein (Ca). In this study, Shr reduced ED1+-macrophages at day 2 (p = 0.013), day 5 (p = 0.006), and day 14 after injury (p = 0.038) compared with Ca, indicating faster resolution of inflammation in Shr. Except for day 2 after injury where Shr led to lower ED1+-macrophages compared with CaH (p = 0.006), both Shr and CaH responded similarly at days 5, 14, and 28 after injury. This findings suggest that beneficial effects of Shr on ED1+-cells might be related to generation of anti-inflammatory peptides through the hydrolysis process, in addition to its high content of anti-inflammatory amino acids. However, while increasing myofiber cross-sectional area in noninjured muscles compared with both Ca and CaH, Shr failed to have a positive effect in corresponding injured muscles. These data indicate that shrimp hydrolysate can facilitate resolution of inflammation after muscle injury mainly through modulating proinflammatory macrophage accumulation but have less effect on optimal recovery in terms of muscle mass and fiber size.

Lean Seafood Intake Reduces Postprandial C-peptide and Lactate Concentrations in Healthy Adults in a Randomized Controlled Trial with a Crossover Design.

BACKGROUND: Recently we showed that lean seafood consumption reduced circulating triacylglycerol (TG) and VLDL concentrations and prevented an elevated total-to-HDL-cholesterol ratio relative to intake of a nonseafood diet. OBJECTIVE: We aimed to elucidate whether diet-induced altered carbohydrate metabolism could be a contributing factor to the previously observed different lipoprotein patterns. METHODS: This was a secondary outcome and explorative randomized controlled trial with a crossover design in 20 healthy adults (7 men and 13 women) that were 50.6 ± 3.4 (mean ± SEM) y old, weighed 75.7 ± 2.5 kg, and had a body mass index (BMI, in kg/m(2)) of 25.6 ± 0.7. After a 3-wk run-in period and separated by a 5-wk wash-out period, the participants consumed 2 balanced diets [in percentage of energy (energy%); 29% fat, 52% carbohydrates, 19% protein] for 4 wk. The diets varied in the main protein sources; 60 energy% of total protein was from either lean seafood or nonseafood sources. On the first and last day of each diet period, fasting and postprandial blood samples were collected before and after consumption of test meals (in energy%; 28% fat, 52% carbohydrates, 20% protein) with cod or lean beef. RESULTS: The diets did not alter serum insulin and glucose concentrations. However, relative to the nonseafood diet period, the lean seafood diet period reduced postprandial C-peptide (P = 0.04) and lactate (P = 0.012) concentrations and fasting and postprandial TG/HDL-cholesterol ratios (P = 0.002). Hence, different postprandial lactate levels occurred at equal glucose concentrations. CONCLUSIONS: Even though the diets did not alter serum insulin and glucose concentrations, intake of the lean seafood compared with the nonseafood diet reduced postprandial concentrations of C-peptide and lactate and the TG/HDL-cholesterol ratio in healthy adults in a manner that may affect the long-term development of insulin resistance, type 2 diabetes, and cardiovascular disease. This trial was registered at www.clinicaltrials.gov as NCT01708681.

Lean-seafood intake decreases urinary markers of mitochondrial lipid and energy metabolism in healthy subjects: Metabolomics results from a randomized crossover intervention study.

SCOPE: Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects. METHODS: In a randomized controlled trial with crossover design, 20 healthy subjects consumed two balanced diets that varied in main protein sources for 4 weeks. Morning spot urine samples were collected before and after each intervention period. Untargeted metabolomics based on (1) H NMR spectroscopy and LC-MS analyses were applied to characterize the urinary metabolic response to the interventions. RESULTS: The lean-seafood diet period reduced the urinary level of l-carnitine, 2,6-dimethylheptanoylcarnitine, and N-methyl-2-pyridone-5-carboxamide, relative to the nonseafood period. The dietary analysis revealed that the higher urinary level of trimethylamine-N-oxide after the lean-seafood diet period and guanidinoacetate and 3-methylhistidine after the nonseafood diet period was related to the endogenous content of these compounds in the diets. CONCLUSIONS: Our data reveal that 4 weeks of lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects after the lean-seafood intake.

Dietary LC-PUFA in iron-deficient anaemic pregnant and lactating guinea pigs induce minor defects in the offsprings' auditory brainstem responses.

OBJECTIVES: We previously demonstrated that a mild pre-natal/early post-natal iron-deficient anaemic (IDA) diet devoid of long-chain polyunsaturated fatty acids (LC-PUFA) affected development, neurophysiology, and cerebral lipid biochemistry of the guinea pigs' progeny. Impacts of dietary LC-PUFA on altered cerebral development resulting from pre-natal IDA are unknown. To address this health issue, impacts of mild gestational IDA in the presence of dietary LC-PUFA on the offsprings' neural maturation were studied in guinea pigs using auditory brainstem responses (ABRs) and assessments of brain fatty acids (FAs). METHODS: Female guinea pigs (n = 10/group) were fed an iron sufficient (IS) or IDA diet (146 and 12.7 mg iron/kg, respectively) with physiological amounts of LC-PUFA, during the gestation and lactation periods. From post-natal day (PNd) 9 onwards, the IS + PUFA diet was given to both groups of weaned offspring. Cerebral tissue and offsprings' ABR were collected on PNd24. RESULTS: There was no difference in peripheral and brainstem transmission times (BTTs) between IS + PUFA and IDA + PUFA siblings (n = 10/group); the neural synchrony was also similar in both groups. Despite the absence of differences in auditory thresholds, IDA + PUFA siblings demonstrated a sensorineural hearing loss in the extreme range of frequencies (32, 4, and 2 kHz), as well as modified brain FA profiles compared to the IS + PUFA siblings. DISCUSSION: The present study reveals that siblings born from dams exposed to a moderate IDA diet including balanced physiological LC-PUFA levels during pregnancy and lactation demonstrate minor impairments of ABR compared to the control siblings, particularly on the auditory acuity, but not on neural synchrony, auditory nerve velocity and BTT.

Lean-seafood intake reduces cardiovascular lipid risk factors in healthy subjects: results from a randomized controlled trial with a crossover design.

BACKGROUND: Observational studies have strongly indicated an association between fish consumption and reduced risk of cardiovascular disease, but data from randomized controlled trials have been inconclusive. OBJECTIVE: Our primary outcome in this study was to elucidate the potentials of the 2 main dietary protein sources lean seafood and nonseafood to modulate fasting and postprandial lipids in healthy subjects. We hypothesized that lean-seafood intake would reduce cardiovascular lipid risk factors in healthy subjects more than would the intake of nonseafood protein sources. DESIGN: This study was a randomized controlled trial with a crossover design. After 3-wk run-in periods and separated by a 5-wk washout period, 20 healthy subjects (7 men and 13 women) consumed 2 balanced diets that varied in main protein sources (60% of total dietary proteins from lean-seafood or nonseafood sources for 4 wk). At days 1 and 28 of each intervention, fasting and postprandial blood samples were collected before and after consumption, respectively, of test meals with cod or lean beef. RESULTS: Relative to the nonseafood intervention, the lean-seafood intervention reduced fasting (relative difference by diets: 0.31 mmol/L; P = 0.03) and postprandial (P = 0.01) serum triacylglycerol concentrations. The lower serum triacylglycerol concentration was associated with reduced fasting triacylglycerol in chylomicrons and very-low-density lipoproteins (VLDLs) (P = 0.004), reduced fasting VLDL particle size (P = 0.04), and a reduced postprandial concentration of medium-sized VLDL particles (P = 0.02). The lean-seafood intervention prevented the elevated ratio of total cholesterol to HDL cholesterol in the fasted serum (P = 0.03) and postprandial serum (P = 0.01) that was observed after the nonseafood intervention. CONCLUSION: The dietary protein source determines fasting and postprandial lipids in healthy individuals in a manner that may have an effect on the long-term development of cardiovascular disease. This study was registered at clinicaltrials.gov as NCT01708681.