Weeks Of Dietary Treatment Research Articles

Exercise mitigates mitochondrial permeability transition pore and quality control mechanisms alterations in nonalcoholic steatohepatitis.

Mitochondrial quality control and apoptosis have been described as key components in the pathogenesis of nonalcoholic steatohepatitis (NASH); exercise is recognized as a nonpharmacological strategy to counteract NASH-associated consequences. We aimed to analyze the effect of voluntary physical activity (VPA) and endurance training (ET) against NASH-induced mitochondrial permeability transition pore (mPTP) opening and mitochondrial and cellular quality control deleterious alterations. Forty-eight male Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 16), standard-diet VPA (n = 8), high-fat diet sedentary (HS, n = 16), and high-fat diet VPA (n = 8). After 9 weeks of diet treatment, half of the SS and HS groups were engaged in an ET program for 8 weeks, 5 days/week, 1 h/day. Liver mPTP susceptibility through osmotic swelling, mPTP-related proteins (cyclophilin D, Sirtuin3, Cofilin-1), markers of mitochondrial biogenesis ((mitochondrial transcription factor A (Tfam) and peroxisome proliferator-activated receptor gamma co-activator protein (PGC-1α)), dynamics (Mitofusin 1 (Mfn1), Mitofusin 2 (Mfn2), Dynamin related protein 1, and Optic atrophy 1)), auto/mitophagy (Beclin-1, microtubule-associated protein 1 light chain 3, p62, PINK1, and Parkin), and apoptotic signaling (Bax, Bcl-2) and caspases-like activities were assessed. HS animals showed an increased susceptibility to mPTP, compromised expression of Tfam, Mfn1, PINK1, and Parkin and an increase in Bax content (HS vs. SS). ET and VPA improved biogenesis-related proteins (PGC-1α) and autophagy signaling (Beclin-1 and Beclin-1/Bcl-2 ratio) and decreased apoptotic signaling (caspases 8 activity, Bax content, and Bax/Bcl-2 ratio). However, only ET decreased mPTP susceptibility and positively modulated Bcl-2, Tfam, Mfn1, Mfn2, PINK1, and Parkin content. In conclusion, exercise reduces the increased susceptibility to mPTP induced by NASH and promotes the increase of auto/mitophagy and mitochondrial fusion towards a protective phenotype.

Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1

Little is known regarding whether adiponectin receptors mediate high-intensity interval training (HIT)-induced improvement of insulin resistance associated with obesity. This study investigated the effect of HIT on whole body insulin resistance in high-fat diet-induced obese mice. 5-week-old male mice (N=30) were randomly assigned to standard chow (SC) (n=10) or HFD (n=20) for 23 weeks. After 15 weeks of dietary treatment, the HFD mice were further assigned to HFD (n=10) or HFD plus HIT (HFD+HIT, n=10). The HFD+HIT mice were subjected to HIT during the last 8 weeks of the 23-week HFD course. HFD resulted in whole body insulin resistance, hypoadiponectinemia, suppressed expression of adiponectin receptor 1(AdipoR1) and 2 (AdipoR2), suppressed expression of phosphorylated AMP-activated protein kinase (p-AMPK) and NAD-dependent deacetylase sirtuin-1 (SIRT1), and decreased mRNAs of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase I (CPT1), and acyl CoA oxidase (ACO) in skeletal muscle. In contrast, HIT alleviated whole body insulin resistance and prevented decreased levels of total adiponectin in both serum and adipose tissue. HIT also prevented the down-regulation of AdipoR1 and AMPK/SIRT1 proteins and the down-regulation of PPARα, CPT1, and ACO mRNAs. The current findings show that HIT alleviates whole body insulin resistance due to HFD-induced obesity via the AdipoR1 and AMPK/SIRT1 mediated-signaling pathway in skeletal muscle, implying the potential role of HIT to combat this metabolic condition.

Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity.

Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

High dietary protein decreases fat deposition induced by high-fat and high-sucrose diet in rats.

High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma β-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver.

Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine.

BackgroundOssabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model.MethodsOssabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24.ResultsThe NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides.ConclusionsThis report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides.

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Objectives While obesity is a major risk factor for preeclampsia, the mechanisms whereby obesity increases this risk are unclear. Since blood pressure regulation during gestation relies greatly on the nitric oxide (NO) system, we aimed to determine the effects of a HFD on blood pressure, fetal outcomes, and endothelial NO synthase (eNOS) levels in pregnant rats. Methods Twelve-week-old Sprague-Dawley female rats were fed a normal diet (ND, 13% fat kcal, n = 5) or a HFD (40% fat kcal, n = 18) ad libitum. Body weight (BW) and total fat mass (FM) were recorded weekly. After 9 weeks of diet treatment, rats were allowed to breed. On gestation day (GD) 19, mean arterial pressure (MAP) was assessed and tissues were harvested. Results Initial BW and FM were similar in ND and HFD groups. On GD19, BW and FM were still similar in ND and HFD rats. There was a trend for MAP to be increased in HFD rats compared to ND rats (116.0 ± 2.7 vs. 106.6 ± 5.0 mmHg). Although HFD did not affected litter size (12.0 ± 1.0 vs. 13.0 ± 0.8 number of fetuses/rat), it reduced fetal weight (2.1 ± 0.0 vs. 2.2 ± 0.0g; P Conclusions While HFD had a detrimental effect on fetal weight, it had no effect on MAP. In addition, although HFD increases eNOS in mesenteric arteries, it seems that this pathway in not important for blood pressure control in HFD treated pregnant rats. Disclosures A.C. Palei: None. F.T. Spradley: None. J.P. Granger: None.

Modulation of amino acid metabolic signatures by supplemented isoenergetic diets differing in protein and cereal fiber content.

Amino-acid (AA) metabolic signatures differ in insulin-resistant (IR) obese vs normal-weight subjects, improve after weight loss, and seem to predict the risk of type 2 diabetes. It is unknown whether weight-maintaining dietary measures aimed at influencing IR alter AA signatures of high-risk subjects. In the randomized controlled Protein, Fiber and Metabolic Syndrome (ProFiMet) trial we investigated effects of four isoenergetic, moderately fat-reduced diets varying in protein and cereal-fiber contents on complete AA metabolic signatures in 76 group-matched overweight or obese high-risk subjects. We analyzed the relation of whole-body and hepatic IR with AA signatures, body fat composition and liver fat, after 0, 6, and 18 weeks of dietary intervention. Discrimination between diets was further enhanced by providing tailored dietary supplements for twice-daily consumption over 18 weeks in all groups. Baseline AA, including branched-chain signatures significantly related to IR, liver fat, and visceral fat mass. Isoenergetic variation of protein and cereal-fiber dietary contents, but not fat restriction, significantly influenced IR, whereas the relation of AA with IR changed with all diets. The tryptophan ratio was significantly suppressed in obese vs overweight participants, but increased after 6 weeks of high cereal-fiber intake to a nonobese phenotype. Modeling analyses revealed diet-induced alterations of complex AA profiles to relate to 70% and 62% of changes in whole-body and hepatic IR. We demonstrate that relatively short-term isoenergetic changes in the diet significantly alter the relation of AA signatures with IR, with possible implications on the determination and treatment of diabetes risk.

Impact of cocoa polyphenol extracts on the immune system and microbiota in two strains of young rats.

A diet containing 10% cocoa, a rich source of polyphenols and fibre, is able to modify intestinal immune status as well as microbiota composition. The present study was aimed at investigating whether cocoa flavonoid content is uniquely responsible for these modulatory effects of cocoa, and to establish whether these effects depend on the rat strain. To this end, 3-week-old Wistar and Brown Norway rats were fed, for 4 weeks, either a standard diet or the following three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0.2% polyphenols (from conventional defatted cocoa), and two others with 0.4 and 0.8% polyphenols (from non-fermented cocoa, very rich in polyphenols). Serum Ig concentrations, faecal IgA levels, microbiota composition and IgA-coating bacterial proportion were evaluated at the beginning and at the end of the study. After the nutritional intervention, the composition of lymphocytes in Peyer's patches and mesenteric lymph nodes was evaluated. In some respects, the Wistar strain was more sensitive to the impact of the cocoa diets than the Brown Norway strain. After 4 weeks of dietary intervention, similar modulatory effects of the diets containing 0.2 and 0.8% polyphenols on mucosal IgA levels and microbiota composition were found, although the 0.2% diet, with a higher proportion of theobromine and fibre, had more impact, suggesting that polyphenols are not the only components involved in such effects.

Abstract 667: The Effects of a High-Fat Diet (HFD) on Blood Pressure in Pregnant Rats

While obesity is a major risk factor for preeclampsia (PE), the mechanisms whereby obesity increases the risk for developing pregnancy-induced hypertension are unclear. Since blood pressure regulation during gestation relies greatly on the nitric oxide (NO) system, we aimed to determine the effects of a HFD on blood pressure and fetal outcomes in pregnant rats treated with NG-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthases. Twelve-week-old Sprague-Dawley female rats were fed a normal diet (ND, 13% fat kcal) or a HFD (40% fat kcal) ad libitum. Body weight (BW) and total fat mass (FM, measured by EchoMRI) were recorded weekly. After 9 weeks of diet treatment, rats were allowed to breed. On gestation day (GD) 14, L-NAME at the concentration 100 mg/L was added to the drinking water of a sub-group of animals (ND + water, n=5; ND + L-NAME, n=6; HFD + water, n=18; HFD + L-NAME, n=16). On GD 19, mean arterial pressure (MAP) was assessed consciously via carotid catheters. Animals were then euthanized and tissues were harvested. Initial BW and FM were similar in ND + water, ND + L-NAME, HFD + water, and HFD + L-NAME (BW: 239.5±4.1 vs. 241.2±4.8 vs. 238.2±2.5 vs. 241.4±2.5 g and FM: 20.4±2.9 vs. 17.9±2.2 vs. 18.2±1.8 vs. 17.4±2.0 g, respectively). By the end of the study, HFD had no effects on BW and FM in pregnant rats (BW: 472.3±5.2 vs. 468.0±10.1 vs. 461.6±12.2 vs. 462.4±8.9 g and FM: 97.5±2.4 vs. 87.3±9.3 vs. 103.3±7.3 vs. 97.5±6.0 g, respectively). Although MAP was elevated in L-NAME treated pregnant rats, HFD did not alter MAP or exacerbate the effect of L-NAME on MAP (106.6±5.0 vs. 131.3±4.9 vs. 116.0±2.7 vs. 130.2±2.8 mmHg, respectively; P<0.05). Neither HFD nor L-NAME affected litter size (13.0±0.8 vs. 13.2±1.2 vs. 12.0±1.0 vs. 12.1±0.8 number of fetuses per rat, respectively). However, HFD reduced fetal weight equally in water and L-NAME treated pregnant rats (2.2±0.0 vs. 2.2±0.1 vs. 2.1±0.0 vs. 2.0±0.0 g, respectively; P<0.05). In summary, while HFD had a detrimental effect on fetal weight, it had no effect on blood pressure regulation during pregnancy.

Effects of feed supplementation with manganese from its different sources on performance and egg parameters of laying hens

The objective of this study was to compare the effects of feed supplementation of laying hens with manganese from its inorganic and organic sources on performance and some parameters of egg quality. Ninety-six hens at 20 weeks of age were randomly allocated to 4 dietary treatments, each consisting of 6 replicates (4 birds per replicate). The control group was fed unsupplemented basal diet (BD) with only natural background Mn level of 46.4 mg/kg feed. For the three experimental treatments, the BD was supplemented with 120 mg Mn/kg either from Mn-sulphate or Mn-chelate of protein hydrolysate (Mn-Pro) or Mn-chelate of glycine hydrate (Mn-Gly). After 8 weeks of dietary treatments the egg production, egg weight, feed intake, and feed efficiency were not affected by dietary treatments. Regardless of the sources, Mn supplementation to feed resulted in significantly decreased percentages of cracked eggs compared to the unsupplemented control group. The thickness, weight, proportion, and index of eggshell were significantly elevated in all groups supplemented with Mn. The intake of Mn-Gly resulted in considerably increased Mn deposition in egg yolk compared to the control eggs. In the control and Mn-sulphate groups yolk malondialdehyde (MDA) started to increase after 20 and 30 days of egg storage respectively, whereas in eggs from hens given organic Mn-sources this parameter was not affected up to 40 days. Although there were no significant differences in MDA values between the treatments until 20 days of storage, the Mn-sulphate group showed significantly higher MDA concentration in yolks compared to the control group after 30 days of storage. These results demonstrate that supplementation of hens’ diet with Mn has positive effects on eggshell quality. Feed supplementation with Mn from organic sources appears to be more effective in preventing yolk lipid oxidation during cold storage of eggs than that from Mn-sulphate.  

High Fat Diet Causes Renal Fibrosis in LDLr-null Mice Through MAPK-NF-κB Pathway Mediated by Ox-LDL

Dyslipidemia, particularly increased LDL-cholesterol level in serum, is associated with atherosclerosis and fibrosis in different organs. This study was designed to investigate the effects of increase in LDL-cholesterol on renal fibrosis. Wild-type (WT) and LDLr knockout (KO) mice were fed standard or high fat diet (HFD), and their kidneys were collected after 26 weeks of dietary intervention for identification of fibrosis and study of potential mechanisms. Additional studies were performed in cultured renal fibroblasts. We observed extensive and diffuse fibrosis in the kidneys of mice given HFD (P < 0.05 vs. standard chow). Fibrosis was associated with enhanced expression of fibronectin, nicotinamide adenine dinucleotide phosphate oxidases and activated p38 and p44/42 mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). There was evidence for accumulation of 4-hydroxynonenal, a lipid peroxidation product, in the kidneys and of ox-LDL in the arteries of LDLr KO mice given HFD. The expression of ox-LDL receptor LOX-1 and of transforming growth factor beta 1 (TGFβ1) was increased in these kidneys. All these changes were more pronounced in LDLr KO mice than in the WT mice. In in vitro studies, treatment of fibroblasts from kidneys of LDLr KO mice with ox-LDL showed intense proliferation and collagen formation (all P < 0.05, fibroblasts from WT mice kidneys). Blockade of p38 MAPK, p44/42 MAPK, or NF-κB significantly attenuated expression of profibrotic signals, collagen formation, and proliferation of fibroblasts. HFD induces renal fibrosis in LDLr-null mice primarily through activation of the nicotinamide adenine dinucleotide phosphate oxidase MAPK-NF-κB pathway by ox-LDL.

Effect of Cholesterol Enriched or Fatty-Acid Diets on Cholesterol and Lipid Levels in Young Wistar Rats

Nutritional intake is a fundamental determinant of health. It is well known that cholesterol rich diets can induce several pathological conditions but detailed mechanism underlying these remains unknown. Wistar rats, an animal strain widely used in the research have been employed to study the effects of dietary interventions due to their metabolic characteristics, which are closer to the human compared to mice. The effect of some components of the western diet, combined with cholesterol in the lipid profile have been studied, but the impact of only cholesterol or fatty-acid diets in such a profile has not been yet characterized. Here we measured the effect of 6 or 16 weeks of dietary intervention with cholesterol enriched diet (CED) or fatty-acid diet (FAD) on cholesterol, triglyceride levels, high density lipoproteins (HDL) and low density lipoproteins (LDL). We observed significant differences in body weight only in animals treated with CED or FAD from Week 9 onwards as compared to animals fed the control diet. There were no differences between animals fed with CED or FAD in cholesterol levels at any time point nevertheless, triglyceride levels were significantly increased as compared to control diet in animals under both diets at early time points. Finally, both CED and FAD induced a decrease in HDL as compared to control levels in treatments of more than 6 weeks, whereas LDL transiently increased in animals treated with FAD from 10 to 12 weeks, but after this period LDL levels returned to baseline, suggesting that young rats have a compensatory effect at least for the period of time analyzed here. Here we provide a temporal course on lipid profile of cholesterol, triglycerides, HDL and LDH in Wistar rats treated with CED and FAD diet that can be useful as reference for future studies.

Isolated Soy Protein-Based Diet Ameliorates Glycemia and Antioxidants Enzyme Activities in Streptozotocin-Induced Diabetes

The objective of this study was to evaluate the changes induced by isolated soy protein (ISP)-based diet on glycemia and oxidative stress biomarkers in diabetic rats. Fifteen male Wistar rats (35 ± 4 g, aged 21 days) were assigned to three groups: Casein (C group), which received casein-based diet during experimental protocol; Diabetic treated with Casein (D + C group) that received casein-based diet before and after diabetes induction; Diabetic treated with ISP (D + S group) that received casein-based diet before diabetes induction and after received ISP-based diet for the experimental protocol. Diabetes was induced by a single dose of streptozotocin (50 mg/kg body weight i.v.). After three weeks of dietary treatment, total nitrates, lipid peroxidation, antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) were measured in heart homogenates. ISP-based diet promoted an improvement in the glycemic levels of diabetic rats compared with casein-based diet (362 ± 25 vs 461 ± 30 mg/dL). CAT activity demonstrated a significant decrease in D + C and D + S groups. D + S group presented a significant increase in SOD and GST activities. Lipid peroxidation was not different among experimental groups. The overall results suggested the potential benefits of ISP-based diet consumption to improve the life quality of diabetic patients.

Glycemic Index Treatment Using Japanese Foods in a Girl With Lennox-Gastaut Syndrome

We introduced a low glycemic index treatment using Japanese ethnic foods to a 13-year-old girl with Lennox-Gastaut syndrome caused by tuberous sclerosis complex. She had previously refused the modified Atkins diet within 2 weeks of diet treatment because of its restrictiveness. The low glycemic index treatment was implemented by limiting the daily carbohydrate intake to 50 g of foods with a glycemic index of less than 50 relative to that of glucose, which included udon, soba, and unpolished Japonica rice with natto. One month after the initiation of the diet therapy, the clusters of tonic seizures for 30 to 60 minutes during sleep were reduced from two or three times per week to once or twice per month, and the frequent myoclonic seizures in the awake state disappeared. She has been on the diet therapy for more than 1 year, and the efficacy of the diet has been sustained. Low glycemic index treatment should be considered for patients with medication-resistant epilepsy who cannot tolerate restrictive diet therapies. Japanese ethnic foods can be used for this diet therapy.

The effects of 3,3′,4,4′-tetrabromobiphenyl on rats fed diets containing a constant level of copper and varying levels of molybdenum

Copper (Cu) metabolism is altered in rats fed diets high in molybdenum (Mo) and low in Cu. This 10-week study was carried out to examine the effects of supplemental Mo (7.5-240 μg/g diet) on male Sprague-Dawley rats fed diets adequate in Cu (5 μg/g diet) and to determine the susceptibility of Mo-treated animals to the environmental pollutant 3,3',4,4'-tetrabromobiphenyl (TBB). After 7 weeks of dietary treatment, half of the rats in each group received a single IP injection of TBB (150 μM/kg bw), while the other half received the corn oil vehicle. Rats sacrificed at 10 weeks showed no effects of Mo on growth, feed efficiency, or selected organ or tissue weights. Dose-dependent effects on plasma Mo (0-5.1 μg/mL), plasma Cu (0.95-0.20 μg/mL), and bone Cu (3.4-10 μg/g) in control through the high dose were found. Cu sequestration in the bone of Mo-treated rats is a new finding. TBB treatment resulted in dramatic weight loss and loss of absolute organ mass. Relative organ weights were increased, except for the thymus. TBB altered the concentrations of certain amino acids. Compared to control rats, this polybrominated biphenyl congener significantly decreased plasma Cu and ceruloplasmin at higher concentrations of dietary Mo and promoted the process of plasma Cu decrease by Mo, suggesting a combined effect.

Anti-obesity effect of kimchi fermented withWeissella koreensisOK1-6 as starter in high-fat diet-induced obese C57BL/6J mice

In this study, we investigated the anti-obesity effects of kimchi (Korean traditional fermented vegetable) fermented either without starter culture or with a specific starter culture, Weissella koreensis OK1-6. C57BL/6J mice were divided into four groups (n = 7); normal diet, HF (high-fat diet), HF-KC (high-fat diet containing 3% kimchi manufactured without starter) and HF-KCO (high-fat diet containing 3% kimchi manufactured with the starter culture W. koreensis OK1-6). After 12 weeks of dietary intervention, the mice were killed, and serum and tissue samples were examined. Serum and hepatic lipid profile, insulin, leptin concentration and expression level of lipid anabolic genes like peroxisome proliferator-activated receptor γ, stearoyl-CoA desaturase-1, liver X receptor α and SREBP2 were significantly decreased (<0.05) along with body and epididymal fat pad weight in the HF-KCO group compared with the HF-KC and HF group. These results suggested that kimchi fermented with the starter W. koreensis OK1-6 has anti-obesity effects in HF-induced obese mice. These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.

Dietary resveratrol does not delay engraftment, sensitize to vincristine or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID mice

Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60–85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. To evaluate the efficacy of dietary resveratrol in vivo, 5-week-old NOD.CB17-Prkdcscid/J mice were fed a control diet or a diet containing 0.2% w/w resveratrol. After 3 weeks of dietary treatment, mice were engrafted with the human t(4;11) ALL line SEM by tail vein injection. Engraftment was monitored by evaluating the presence of human CD19+ cells in peripheral blood using flow cytometry. Relative to control diet, dietary resveratrol did not delay the engraftment of the leukemia cells. To determine if dietary resveratrol could increase efficacy of a chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the control or supplemented diet. Survival curves and monitoring the percentage of human leukemia cells in peripheral blood showed that resveratrol did not inhibit leukemia cell growth or influence the activity of vincristine. Mass spectrometric analysis of mouse serum revealed that the majority of resveratrol was present as glucuronidated and sulfated metabolites. These data do not support the concept that dietary resveratrol has potential as a preventative agent against the growth of high-risk t(4;11) ALL.

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.

Diet‐Induced Obesity Resistance of Kv1.3−/− Mice is Olfactory Bulb Dependent

Gene-targeted deletion of the voltage-gated potassium channel, Kv1.3 (Kv1.3-/-), increases olfactory sensitivity and discriminatory ability, and causes resistance to diet-induced obesity (DIO) in mice. The present study aimed to determine whether the enhanced olfactory ability of the Kv1.3-/- mouse contributes to the resistance to DIO. Kv1.3+/+ and Kv1.3-/- mice were subject to bilateral olfactory bulbectomy (OBX) or sham surgery at 9 weeks of age and placed on either a control chow diet or a 32% moderately high-fat diet (MHF). Caloric and water intake, locomotor activity and oxygen consumption were monitored after 5 weeks of diet treatment. At the end of 26 weeks of diet treatment, fat pad weight and blood chemistry were evaluated. Kv1.3+/+ mice exhibited a significant increase in weight, adiposity, fasting glucose and fasting leptin in response to the MHF-diet, with or without OBX. When treated with a MHF-diet, Kv1.3-/- mice gained significantly less weight than Kv1.3+/+ mice and exhibited a significant increase in light phase metabolism. OBX of Kv1.3-/- mice prevented the resistance to DIO and concomitant up-regulation of light phase metabolism at the same time as decreasing dark phase metabolism and total energy expenditure. These findings suggest that pathways activated in Kv1.3-/- that increased energy expenditure and led to resistance to DIO are olfactory bulb dependent. Thus, these findings add to a growing body of evidence suggesting that the olfactory system can modulate the pathways involved in the regulation of energy balance.

Consumption of dehydrated Opuntia ficus Indica (nopal) prevents the development of fatty liver by modifying hepatic lipid metabolism in obese Zucker fa/fa rats

Opuntia ficus indica (nopal), a plant rich in bioactive compounds, has been widely used in the traditional Mexican medicine to treat diabetes. Therefore in the present study, we investigated the effect of nopal consumption in the prevention of fatty liver in obese Zucker rats.Six weeks old male Zucker (fa/fa) rats (n=12 per group) were fed with a control diet (AIN‐93G; C) or C+ Nopal for 7 weeks. After 7 weeks of dietary treatment, rats fed C+nopal decreased by 50% hepatic triglycerides with respect to control and reduced hepatomegaly and macrovesicular steatosis. In addition, increased serum levels of adiponectin, mRNA expression of genes involved in lipid oxidation (PPARα, CPT1 and ACOX) and lipid export (MTTP and PLTP), hepatic CPT1 and MTTP protein levels. Furthermore, rats fed C+nopal decreased postprandial serum insulin levels; increased liver pAkt/Akt ratio in the postprandial state and significantly decreased serum ALT and AST levels.This study shows that nopal consumption prevents the development of fatty liver in obese Zucker rats by increasing fatty acid oxidation and VLDL synthesis,, improving liver insulin signaling. Supported by Grupo Produce DF 2010 (to NT)Grant Funding Source: Produce