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Head of Institute: Prof. Oren Tirosh

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Robert H. Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, 
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Weintraub, Y. ; Cohen, S. ; Chapnik, N. ; Ben-Tov, A. ; Yerushalmy-Feler, A. ; Dotan, I. ; Tauman, R. ; Froy, O. Clock Gene Disruption Is an Initial Manifestation of Inflammatory Bowel Diseases. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2020, 18, 115+.Abstract
BACKGROUND & AIMS: Sleep disruption modifies the immune system and can trigger flares of inflammatory bowel diseases (IBD). Changes in expression of clock genes have been reported in patients with IBD. We investigated whether a change in the circadian clock is an early event in development of IBD. METHODS: We performed a prospective study of patients younger than 21 years old who underwent diagnostic endoscopies at the pediatric and adult gastroenterology units at the Tel Aviv Sourasky Medical Center from August 2016 through August 2017. Questionnaires were completed by 32 patients with IBD (8-21 years old) and 18 healthy individuals (controls) that provided data on demographics, sleep, disease activity scores. We also obtained data on endoscopic scores, anthropometric parameters, blood level of C-reactive protein (CRP), and fecal level of calprotectin. Peripheral blood and intestinal mucosa samples were analyzed for expression levels of clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1, and PER2). RESULTS: Levels of CRP and fecal calprotectin were significantly higher in patients with IBD compared with controls (P<.05). Expression levels of clock genes (CLOCK, CRY1, CRY2, PER1, and PER2) were significantly lower in inflamed intestinal mucosa from patients compared with intestinal mucosa from controls (P<.05). Expression levels of all clock genes except for PER2, were also significantly lower in non-inflamed intestinal mucosal tissues from patients compared with controls (P<.05). Expression levels of clock genes (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) were lower in white blood cells from patients with IBD compared with controls. This reduction was greater in white blood cells from patients with ulcerative colitis than in patients with Crohn's disease. CONCLUSION: Young, newly diagnosed, untreated patients with IBD have reduced expression of clock genes in inflamed and non-inflamed intestinal mucosal samples, and also in blood cells, compared with healthy individuals. Alterations in expression of clock genes might be an early event in IBD pathogenesis.
Guttman, Y. ; Yedidia, I. ; Nudel, A. ; Zhmykhova, Y. ; Kerem, Z. ; Carmi, N. New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity. FOOD AND CHEMICAL TOXICOLOGY 2020, 137.Abstract
Furanocoumarins are the main compounds responsible for the food-drug interactions known as the grapefruit effect, which is caused by the inhibition of CYP3A4-mediated drug metabolism. We evaluated the effects of two new, low-furanocoumarin grapefruit cultivars on CYP3A4 activity and the roles of different furanocoumarins, individually and together with other juice compounds, in the inhibition of CYP3A4 by grapefruit. Whereas a standard grapefruit cultivar inhibited CYP3A4 activity in a dose-dependent manner, neither of the two examined low-furanocoumarin cultivars had an inhibitory effect. Despite the fact that bergamottin and 6',7'-dihydroxybergamottin are weak inhibitors of CYP3A4, their relatively high levels in grapefruit make them the leading cause of the grapefruit effect. We found that furanocoumarins together with other juice compounds inhibit CYP3A4 in an additive manner. In silico docking simulation was employed, and differentiated between high- and low-potency inhibitors, suggesting that modeling may be useful for identifying potentially harmful food-drug interactions.
Bimro, E. T. ; Hovav, R. ; Nyska, A. ; Glazer, T. A. ; Madar, Z. High oleic peanuts improve parameters leading to fatty liver development and change the microbiota in mice intestine. FOOD & NUTRITION RESEARCH 2020, 64.Abstract
Background: Oleic-acid consumption can possibly prevent or delay metabolic diseases. In Israel, a Virginia-type peanut cultivar with a high content of oleic acid has been developed. Objective: This study examined the effect of consuming high oleic peanuts (D7) on the development of fatty liver compared to the standard HN strain. Design: The two peanut cultivars were added to normal diet (ND) and high-fat (HF) mouse diet. Male C57B1/6 mice were fed for 8 and 10 weeks on a 4% D7, 4% HN, or control diet. At the end of the experiments, blood and tissues were collected. Triglyceride, lipid levels, histology, and protein expression were examined. The diets' effects on intestinal microbiota were also evaluated. Results: Both D7 and HFD7 led to a reduction in plasma triglycerides. Lipids, triglycerides, and free fatty acids in the liver were low in diets containing D7. Additionally. CD36 expression decreased in the D7 group. Consumption of D7 led to higher Prevotella levels, and consumption of ND that contained HN or D7 led to a lower Firmicutes/Bacteroidetes ratio. Conclusion: These findings suggest that consumption of peanuts high in oleic acid (D7) may have the potential to delay primary fatty liver symptoms.
Palman, Y. ; De Leo, R. ; Pulvirenti, A. ; Green, S. J. ; Hayouka, Z. Antimicrobial peptide cocktail activity in minced turkey meat. FOOD MICROBIOLOGY 2020, 92.Abstract
Meat products contain valuable nutrients that are important for human health and development but are also highly susceptible to colonization by microorganisms. This can lead to spoilage and serious foodborne illnesses. Natural antimicrobial peptides, produced by many organisms as part of their innate immune system to fight microbial infections, have great potential as food preservatives. In this study, we explored the effect of ternary antimicrobial random peptide mixtures (RPMs) on food spoilage bacteria in minced turkey meat. Amendment of RPMs to meat led to significant reductions in bacterial abundance in experimental tests, and RPMs worked synergistically with nitrite to reduce bacterial loads. Using high-throughput 16S ribosomal RNA gene amplicon sequencing, we characterized the effect of RPMs and nitrite on meat microbial community structure before and during incubation under refrigerated conditions. Our findings reveal strong antimicrobial activity for RPMs against spoilage bacteria in meat, including Listeria monocytogenes and Pseudomonas putida. These results demonstrate the potential of RPMs as a safer preservative for reducing spoilage in meat and other food products.
Sason, G. ; Nussinovitch, A. Selective protective coating for damaged pomegranate arils. FOOD HYDROCOLLOIDS 2020, 103.Abstract
This is the first report on a method to create a selective protective coating (i.e., ``bandage'') to treat only the damaged part of pomegranate arils for shelf-life extension of these ready-to-eat chilled fruit. Implementation of a specific sequence of steps enabled the formation of an edible alginate-based protective gel layer only on the damaged surface of the aril. The consecutive steps included immersion of the arils in a solution containing a crosslinking agent, followed by immersion in an aqueous solution consisting of a polysaccharide, and then drying of the arils at ambient temperature. The selective coating method relies on the difference between the hydrophobic natural aril skin and the hydrophilic damaged parts of the aril. The formed coating was thin, transparent and sensorially undetectable, as demonstrated by triangle test. The formed coating helped preserve product quality and decreased fluid exudation during storage. The straightforward method for creating this selective coating may also be valid for any injured or cut plant tissue.
Assa-Glazer, T. ; Gorelick, J. ; Sela, N. ; Nyska, A. ; Bernstein, N. ; Madar, Z. Cannabis Extracts Affected Metabolic Syndrome Parameters in Mice Fed High-Fat/Cholesterol Diet. CANNABIS AND CANNABINOID RESEARCH 2020, 5 202-214.Abstract
Introduction:Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis may potentially be beneficial for treating metabolic disorders such as NAFLD, the effects of cannabis on liver diseases and gut microbiota profile are yet to be addressed. In this study, we evaluated the therapeutic effects of cannabis strains with different cannabinoid profiles on NAFLD progression. Materials and Methods:NAFLD was induced by feeding mice a high-fat/cholesterol diet (HFCD) for 6 weeks. During this period, cannabis extracts were administrated orally at a concentration of 5 mg/kg every 3 days. Profile of lipids, liver enzymes, glucose tolerance, and gene expression related to carbohydrate lipid metabolism and liver inflammation were analyzed. The effect of cannabis strains on microbiota composition in the gut was evaluated. Results:A cannabidiol (CBD)-rich extract produced an increase in inflammatory related gene expression and a less diverse microbiota profile, associated with increased fasting glucose levels in HFCD-fed mice. In contrast, mice receiving a tetrahydrocannabinol (THC)-rich extract exhibited moderate weight gain, improved glucose response curves, and a decrease in liver enzymes. Conclusions:The results of this study indicate that the administration of cannabis containing elevated levels of THC may help ameliorate symptoms of NAFLD, whereas administration of CBD-rich cannabis extracts may cause a proinflammatory effect in the liver, linked with an unfavorable change in the microbiota profile. Our preliminary data suggest that these effects are mediated by mechanisms other than increased expression of the endocannabinoid receptors cannabinoid receptor 1 (CB1) and CB2.
Anavi, S. ; Tirosh, O. iNOS as a metabolic enzyme under stress conditions. FREE RADICAL BIOLOGY AND MEDICINE 2020, 146, 16-35.Abstract
Nitric oxide (NO) is a free radical acting as a cellular signaling molecule in many different biochemical processes. NO is synthesized from L-arginine through the action of the nitric oxide synthase (NOS) family of enzymes, which includes three isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS). iNOS-derived NO has been associated with the pathogenesis and progression of several diseases, including liver diseases, insulin resistance, obesity and diseases of the cardiovascular system. However, transient NO production can modulate metabolism to survive and cope with stress conditions. Accumulating evidence strongly imply that iNOS-derived NO plays a central role in the regulation of several biochemical pathways and energy metabolism including glucose and lipid metabolism during inflammatory conditions. This review summarizes current evidence for the regulation of glucose and lipid metabolism by iNOS during inflammation, and argues for the role of iNOS as a metabolic enzyme in immune and non-immune cells.
Cheriker, H. ; Stern Bauer, T. ; Oren, Y. ; Nir, S. ; Hayouka, Z. Immobilized random peptide mixtures exhibit broad antimicrobial activity with high selectivity. CHEMICAL COMMUNICATIONS 2020, 56, 11022-11025.Abstract
In the current study, we evaluated the antimicrobial activity of randomly-sequenced peptide mixtures (RPMs) bearing hydrophobic and cationic residues thatwere immobilized on beads. We showed that these beads exhibit high and broad bactericidal activity against various pathogenic bacteria while possessing minimal hemolytic activity.
Altberg, A. ; Hovav, R. ; Chapnik, N. ; Madar, Z. Effect of dietary oils from various sources on carbohydrate and fat metabolism in mice. FOOD & NUTRITION RESEARCH 2020, 64.Abstract
Background: Dietary oils differ in their fatty acid composition and the presence of additional microcomponents (antioxidants, etc.). These differences are thought to invoke different biochemical pathways, thus affecting fats and carbohydrates metabolism differently. Olive oil (OO) and soybean oil (SO) are common vegetable oils in the local cuisine. Peanuts oils of local varieties are viewed as potential sources of dietary vegetable oils, especially in the food industry. Objective: We examined the effect of four different dietary vegetable oils on carbohydrate and lipid metabolism in mice. The selected oils were OO, high in oleic acid, extracted from cultivated high oleic acid peanut (C-PO), regular peanut oil (PO), and SO. Design: In this study, 32 male C57BL/6J mice were randomly divided into four groups (n = 8 in each group) and were fed with four different diets enriched with 4% (w/w) dietary vegetable oils (OO, C-PO, PO, or SO). After 10 weeks, the mice were sacrificed. Western blot was used to examine proteins such as phospho-AMP-activated protein kinase (p-AMPK), ace-tyl-CoA carboxylase (ACC), cluster of differentiation 36 (CD36), and Sirtuin 1 (SIRT1), whereas real-time polymerase chain reaction (PCR) was used to examine the expression of sterol regulatory element-binding protein-lc (SREBP-IC), fatty acid synthase (FAS), glucose-6-phosphatase (G6Pase), and CD36 transcripts. Results: In mice-fed SO, lipid accumulation was predominately in adipose tissue, accompanied a tendency decrease in insulin sensitivity. Mice-fed OO had lower plasma triglycerides (TG) and increased hepatic CD36 gene expression. The C-PO group presented lower messenger RNA (mRNA) levels in the liver for all examined genes: SREBP-1c, FAS, G6Pase, and CD36. There were no significant differences in weight gain, plasma cholesterol and high-density lipoprotein (HDL) cholesterol levels, hepatic ACC, SIRT1, AMPK, and CD36 protein levels or in liver function among the diets. Discussion: It seems that as long as fat is consumed in moderation, oil types may play a lesser role in the metabolism of healthy individuals. Conclusion: This finding has the potential to increase flexibility in choosing oil types for consumption.
Dadon-Freiberg, M. ; Chapnik, N. ; Froy, O. REV-ERB alpha activates the mTOR signalling pathway and promotes myotubes differentiation. BIOLOGY OF THE CELL 2020, 112, 213-221.Abstract
Background Information Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell and whole-body energy homoeostasis. REV-ERB alpha is a nuclear receptor that plays an important role in metabolism. While mTORC1 activation is necessary for muscle differentiation, the role of REV-ERB alpha is less clear. Results We studied the effect of REV-ERB alpha overexpression and silencing as well as mTORC1 activation and inhibition on the differentiation of C2C12 myoblasts to myotubes. mTOR, myogenin and REV-ERB alpha were induced during differentiation of myoblasts into myotubes. REV-ERB alpha was found to activate mTORC1 during the differentiation process even in the absence of the differentiation medium. This activation was presumably through the downregulation of the expression of TSC1, an mTORC1 inhibitor. Conclusion Herein we show that REV-ERB alpha promotes myoblasts differentiation via the activation of the mTORC1 signalling pathway. Significance REV-ERB alpha modulation can activate mTORC1 signalling and promote myoblasts differentiation.
Topman-Rakover, S. ; Malach, E. ; Burdman, S. ; Hayouka, Z. Antibacterial lipo-random peptide mixtures exhibit high selectivity and synergistic interactions. CHEMICAL COMMUNICATIONS 2020, 56, 12053-12056.Abstract
Random peptide mixtures (RPMs) have been recently proposed as powerful antimicrobial compounds. These are unique mixtures of peptides synthesized by random combination of a cationic and a hydrophobic amino acid. Here, we introduce a new type of antimicrobial compounds, short lipo-RPMs, which result fromN-palmitoylation of RPMs. We report the characterization of 5-mer lipo-RPMs containingl-phenylalanine andd-lysine, named p-FdK5. p-FdK5 had high antibacterial activity against several bacterial strains and was able to reduce disease severity caused by a plant pathogen. We further synthesized and studied all 32 (2(5)) possible lipopeptides that compose the p-FdK5 mixture. We showed that the antibacterial activity of specific lipopeptides depends on the peptide hydrophobicity and on the location of the hydrophobic amino acids relative to the palmitic acid. Interestingly, synergism assays revealed positive interactions between different sequence-specific lipopeptides in terms of antimicrobial activity.
Froy, O. Response to Comment on Jakubowicz et al. Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial. Diabetes Care 2019;42:2171-2. DIABETES CARE 2020, 43, E13-E14.
Teboul, N. ; Gadri, Y. ; Berkovich, Z. ; Reifen, R. ; Peleg, Z. Genetic Architecture Underpinning Yield Components and Seed Mineral-Nutrients in Sesame. GENES 2020, 11.Abstract
Genetic dissection of yield components and seed mineral-nutrient is crucial for understanding plant physiological and biochemical processes and alleviate nutrient malnutrition. Sesame (Sesamum indicum L.) is an orphan crop that harbors rich allelic repertoire for seed mineral-nutrients. Here, we harness this wide diversity to study the genetic architecture of yield components and seed mineral-nutrients using a core-collection of worldwide genotypes and segregating mapping population. We also tested the association between these traits and the effect of seed nutrients concentration on their bio-accessibility. Wide genetic diversity for yield components and seed mineral-nutrients was found among the core-collection. A high-density linkage map consisting of 19,309 markers was constructed and used for genetic mapping of 84 QTL associated with yield components and 50 QTL for seed minerals. To the best of our knowledge, this is the first report on mineral-nutrients QTL in sesame. Genomic regions with a cluster of overlapping QTL for several morphological and nutritional traits were identified and considered as genomic hotspots. Candidate gene analysis revealed potential functional associations between QTL and corresponding genes, which offers unique opportunities for synchronous improvement of mineral-nutrients. Our findings shed-light on the genetic architecture of yield components, seed mineral-nutrients and their inter- and intra- relationships, which may facilitate future breeding efforts to develop bio-fortified sesame cultivars.
Goldstein, I. Chromatin Regulation and Transcription Factor Cooperation in Liver Cells. In LIVER: BIOLOGY AND PATHOBIOLOGY, 6TH EDITION, 6 EDITION; Arias, I. M. ; Alter, H. J. ; Boyer, J. L. ; Cohen, D. E. ; Shafritz, D. A. ; Thorgeirsson, S. S. ; Wolkoff, A. W., Ed. LIVER: BIOLOGY AND PATHOBIOLOGY, 6TH EDITION, 6 EDITION; 2020; pp. 1043-1049.
Dolev, N. ; Katz, Z. ; Ludmer, Z. ; Ullmann, A. ; Brauner, N. ; Goikhman, R. Natural amino acids as potential chelators for soil remediation. ENVIRONMENTAL RESEARCH 2020, 183.Abstract
The soils contaminated by toxic metals are often remediated using EDTA and similar non-biodegradable chelators. Most chelators are in fact synthetic amino acid derivatives, whereas natural proteinogenic amino acids (PAAs) have not been systematically explored as remediation agents, despite their well-known metal chelating abilities and environmental benefits. Our study represents a comprehensive research exploring 16 structurally and functionally different PAAs as potential remediating agents, applied to 3 different heavy metal-contaminated samples. The study was mostly focused on extracting Cd, Cu, Ni, and Zn. The reaction parameters were screened and optimized. It was found that the efficiencies of extracting Cu, Ni, and Zn by Threonine, Aspartic acid and Histidine were comparable to those by EDTA, whereas non-polar side chain-containing PAAs demonstrated consistently lower PTM extraction rates compared to other PAAs. The sulfur-containing Cysteine appeared to be efficient to extract Cd (to some extent), Ni and Zn, but not Cu, due to chemical reasons. The structure-functional correlations were identified, described, and found to be independent on the specific samples. Possible molecular mechanisms of metal extraction from soils by PAAs are discussed. In contrast to EDTA, the soil-essential elements are almost not extracted by PAAs. This important feature of the PAAs, along with their availability, observed selectivity, competitive efficiency, non-toxicity and even fertilizing properties, make them particularly soil-friendly, and thus, potentially applicable chelators in certain remediation processes.
Kaminsky-Kolesnikov, Y. ; Rauchbach, E. ; Abu-Halaka, D. ; Hahn, M. ; Garcia-Ruiz, C. ; Fernandez-Checa, J. C. ; Madar, Z. ; Tirosh, O. Cholesterol Induces Nrf-2-and HIF-1 alpha-Dependent Hepatocyte Proliferation and Liver Regeneration to Ameliorate Bile Acid Toxicity in Mouse Models of NASH and Fibrosis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020, 2020.Abstract
Nonalcoholic steatohepatitis (NASH) is currently one of the most common liver diseases worldwide. The toxic effects of lipids and bile acids contribute to NASH. The regenerative pathway in response to damage to the liver includes activation of the inflammatory process and priming of hepatocytes to proliferate to restore tissue homeostasis. However, the effects of cholesterol on bile acid toxicity, inflammation, and fibrosis remain unknown. We have used two mouse models of bile acid toxicity to induce liver inflammation and fibrosis. A three-week study was conducted using wild-type mice receiving an atherogenic diet (1% (w/w) cholesterol and 0.5% (w/w) cholic acid) and its separate constituents. Mdr2-/- mice were fed a high-cholesterol-enriched diet or standard AIN-93 diet for 6 weeks. We measured serum transaminase levels to assess liver tissue necrosis and fibrosis; iNOS, SAA1, SAA2, and F4/80 levels to determine liver inflammation; PCNA and HGF levels to evaluate proliferative response; and Nrf-2, HIF-1 alpha, and downstream gene expression to establish protective responses. In both studies, high bile acid levels increased serum transaminases and liver fibrosis, whereas cholesterol supplementation attenuated these effects. Cholesterol supplementation activated survival and the robustness of HIF-1 alpha and Nrf-2 gene expression in hepatocytes, induced liver inflammation and hepatocyte proliferation, and inhibited stellate cell hyperplasia and fibrosis. In conclusion, our data show for the first time that cholesterol intake protects against bile acid liver toxicity. The balance between hepatic cholesterol and bile acid levels may be of prognostic value in liver disease progression and trajectory.
Shumeiko, V. ; Paltiel, Y. ; Bisker, G. ; Hayouka, Z. ; Shoseyov, O. A Paper-Based Near-Infrared Optical Biosensor for Quantitative Detection of Protease Activity Using Peptide-Encapsulated SWCNTs. SENSORS 2020, 20.Abstract
A protease is an enzyme that catalyzes proteolysis of proteins into smaller polypeptides or single amino acids. As crucial elements in many biological processes, proteases have been shown to be informative biomarkers for several pathological conditions in humans, animals, and plants. Therefore, fast, reliable, and cost-effective protease biosensors suitable for point-of-care (POC) sensing may aid in diagnostics, treatment, and drug discovery for various diseases. This work presents an affordable and simple paper-based dipstick biosensor that utilizes peptide-encapsulated single-wall carbon nanotubes (SWCNTs) for protease detection. Upon enzymatic digestion of the peptide, a significant drop in the photoluminescence (PL) of the SWCNTs was detected. As the emitted PL is in the near-infrared region, the developed biosensor has a good signal to noise ratio in biological fluids. One of the diseases associated with abnormal protease activity is pancreatitis. In acute pancreatitis, trypsin concentration could reach up to 84 mu g/mL in the urine. For proof of concept, we demonstrate the feasibility of the proposed biosensor for the detection of the abnormal levels of trypsin activity in urine samples.
Singh, R. P. ; Abu Halaka, D. ; Hayouka, Z. ; Tirosh, O. High-Fat Diet Induced Alteration of Mice Microbiota and the Functional Ability to Utilize Fructooligosaccharide for Ethanol Production. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 2020, 10.Abstract
High-fat diet (HFD) leads to enhancement in various parameters of mice like weight, fasting glucose levels, adipose tissue, and also the liver weight in male C57 BL/6 J mice. Additionally, high-fat diet causes severe liver damage with significant increase in the level of aspartate amino transferase (AST) and alanine transaminase (ALT). The variations in microbiota induced by different diet were analyzed by Illumina MiSeq platform with sequencing of 16S ribosomal RNA (rRNA) gene, and QIIME pipeline was used. The population of Proteobacteria was found to be higher in HFD cecum sample as compared to other treatments. Microbiota analysis suggests that phylum Proteobacteria and Firmicutes were found to be higher in high-fat diet groups as compared to mice fed with normal diet (ND). At the genus level,Bacteroidesshowed higher population in HFD diet. Bacterial strains belonging toEnterobacteriaceaelikeEscherichia, Klebsiella, andShigellawere also dominant in HFD treatments. Furthermore, we explored the effects of ethanol productionin vitrowith supplementation of dietary fibers following inoculation of ND and HFD microbiotas. HFD microbiota of cecum and feces showed high level (P< 0.05) of ethanol production with 2% fructooligosaccharide (FOS) as compared to 2% galactomannan. Microbial fermentation also generated short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. High levels (P< 0.05) of propionate were found after fermentation of FOS with HFD cecum and feces microbiota. The present study highlights the HFD-induced population of phylum Proteobacteria and genusBacteroidesfor ethanol production using FOS as a dietary supplement, and these findings may imply on the harmful effect of HFD even at the microbiota level.
Rozner, R. ; Vernikov, J. ; Griess-Fishheimer, S. ; Travinsky, T. ; Penn, S. ; Schwartz, B. ; Mesilati-Stahy, R. ; Argov-Argaman, N. ; Shahar, R. ; Monsonego-Ornan, E. The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development. Nutrients 2020, 12. Publisher's VersionAbstract
N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.
Ofir, O. ; Buch, A. ; Rouach, V. ; Goldsmith, R. ; Stern, N. ; Monsonego-Ornan, E. Association between abdominal obesity and fragility fractures among elderly Israeli women. 2020, 32, 1459 - 1467. Publisher's VersionAbstract
Obesity has been traditionally viewed as a protective factor for fractures. Recent studies have challenged this concept, particularly regarding abdominal obesity. We aimed to investigate the association between abdominal obesity, body mass index (BMI) and fragility fractures prevalence in a sample of community-dwelling elderly Israeli women.