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Nature Microbiology Aug 2023Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary...
Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by C-inulin. Integration of C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease.
Topics: Animals; Mice; Non-alcoholic Fatty Liver Disease; Inulin; Fatty Acids; Inflammation; Dietary Fiber
PubMed: 37386075
DOI: 10.1038/s41564-023-01418-7 -
The American Journal of Clinical... Mar 2024Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD.
OBJECTIVES
To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD.
METHODS
In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed.
RESULTS
In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss.
CONCLUSION
Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome.
TRIAL REGISTRATION NUMBER
This trial was registered at the clinicaltrials.gov as NCT05259475.
Topics: Female; Humans; Non-alcoholic Fatty Liver Disease; Diet, Mediterranean; Liver; Weight Loss; Fatty Acids, Unsaturated; Cholesterol; Fatty Acids
PubMed: 38035997
DOI: 10.1016/j.ajcnut.2023.11.013 -
Nutrients Oct 2023Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0...
Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.
Topics: Humans; Longevity; Diabetes Mellitus, Type 2; Fatty Acids, Essential; Sirolimus
PubMed: 37960259
DOI: 10.3390/nu15214607 -
The Chinese Journal of Physiology 2023Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0%...
Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Chromatography, Liquid; Prospective Studies; Tandem Mass Spectrometry; Metabolome; Myocardium; Carbohydrates
PubMed: 38149568
DOI: 10.4103/cjop.CJOP-D-23-00126 -
Frontiers in Nutrition 2023Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the...
OBJECTIVE
Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the impact of dietary components on different metabolomic profiles in primary tissues of mice.
METHODS
For 8 weeks, diet with high-glucose or-fat was given to C57BL/6 J mice. The levels of metabolites in the primary tissues of mice were studied using gas chromatography-mass spectrometry (GC-MS) and analyzed using multivariate statistics.
RESULTS
By comparing the metabolic profiles between the two diet groups and control group in mice main tissues, our study revealed 32 metabolites in the high-glucose diet (HGD) group and 28 metabolites in the high-fat diet (HFD) group. The most significantly altered metabolites were amino acids (AAs; L-alanine, L-valine, glycine, L-aspartic acid, L-isoleucine, L-leucine, L-threonine, L-glutamic acid, phenylalanine, tyrosine, serine, proline, and lysine), fatty acids (FAs; propanoic acid, 9,12-octadecadienoic acid, pentadecanoic acid, hexanoic acid, and myristic acid), and organic compounds (succinic acid, malic acid, citric acid, L-(+)-lactic acid, myo-inositol, and urea). These metabolites are implicated in many metabolic pathways related to energy, AAs, and lipids metabolism.
CONCLUSION
We systematically analyzed the metabolic changes underlying high-glucose or high-fat diet. The two divergent diets induced patent changes in AA and lipid metabolism in the main tissues, and helped identify metabolic pathways in a mouse model.
PubMed: 37492592
DOI: 10.3389/fnut.2023.1171806 -
Natural Product Research 2023In the present study, we report herein the isolation of cadinane-type sesquiterpenoid, tatarinowin A (ACH-6), and pentadecanoic acid (ACH-8) from petroleum ether extract...
In the present study, we report herein the isolation of cadinane-type sesquiterpenoid, tatarinowin A (ACH-6), and pentadecanoic acid (ACH-8) from petroleum ether extract of rhizome of (Acoraceae) along with 6 other known compounds in this species. It is pertinent to mention here that this is the first report to stain these compounds in which dereplication approach based on GC-MS was applied to target unknown compounds ACH-6 and ACH-8 in Derelpication approaches based on GC-MS is very useful technique in the area of drug discovery and have eminence potential to identify known and unknown compounds present in extracts of medicinal important plants. This technique can be used to expedite the process of purification of unknown compounds from different matrixes. The isolated compounds were identified with the help of inbuilt library search which reveals the presence of 17 known and 4 unknown compounds. Further, the structure elucidation of all isolated compounds was done using spectroscopy techniques. Also, the structure of ACH-6 was further confirmed by using the single-crystal X-ray diffraction technique.
Topics: Acorus; Gas Chromatography-Mass Spectrometry; Plant Extracts; Plants, Medicinal; Rhizome
PubMed: 35382654
DOI: 10.1080/14786419.2022.2061482 -
Microorganisms Sep 2023Rhizosphere microorganisms and the volatile organic compounds (VOCs) produced by them take part in the regulation of the chemotaxis of nematodes. A total of 150 strains...
Rhizosphere microorganisms and the volatile organic compounds (VOCs) produced by them take part in the regulation of the chemotaxis of nematodes. A total of 150 strains of rhizosphere bacteria were screened via a chemotaxis experiment with . Some isolates affected the behavior of the nematodes, including attraction, randomness, and repulsion. Volatile metabolites produced via the selected bacteria were associated with the chemotaxis of nematodes. was highly attracted to decanal. In addition, dimethyl disulfide, 2,5-dimethylpyrazine, pentadecanoic acid, and palmitic acid were found to attract weakly . Furthermore, the chemotaxis of was tested in a pot experiment. The bacteria sp. 1-50, 2-35, 5-14, 6-4, and VOC decanal could regulate the movement of M. incognita in the pot with or without plants. The results provide insights into rhizosphere microorganisms and their VOCs and how they regulate the chemotaxis of the nematodes.
PubMed: 37764115
DOI: 10.3390/microorganisms11092271 -
Molecules (Basel, Switzerland) Nov 2023Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang...
Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang Dynasty. (HK) is the most common seahorse species in the medicinal material market and is one of the genuine sources of medicinal seahorse documented in the Chinese pharmacopeia. It is mainly cultivated in the Shandong, Fujian, and Guangxi Provinces in China. However, pseudo-HK, represented by (HI) due to its similar appearance and traits, is often found in the market, compromising the safety and efficacy of clinical use. Currently, there is a lack of reliable methods for identifying these species based on their chemical composition. In this study, we employed, for the first time, a strategy combining gas chromatography-mass spectrometry (GC-MS) fingerprints and chemical patterns in order to identify HK and HI; it is also the first metabolomic study to date of HI as to chemical components. The obtained results revealed remarkable similarities in the chemical fingerprints, while significant differences were also observed. By employing hierarchical cluster analysis (HCA) and principal component analysis (PCA), based on the relative contents of their characteristic peaks, all 34 samples were successfully differentiated according to their species of origin, with samples from the same species forming distinct clusters. Moreover, nonadecanoic acid and behenic acid were exclusively detected in HK samples, further distinguishing them from HI samples. Additionally, the relative contents of lauric acid, tetradecanoic acid, pentadecanoic acid, n-hexadecanoic acid, palmitoleic acid, margaric acid, oleic acid, fenozan acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) exhibited significant differences between HK and HI ( < 0.0001), as determined by an unpaired -test. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified seven components (DHA, EPA, n-hexadecanoic acid, tetradecanoic acid, palmitoleic acid, octadecanoic acid, and margaric acid) with high discriminatory value (VIP value > 1). Thus, nonadecanoic acid, behenic acid, and these seven compounds can be utilized as chemical markers for distinguishing HK from HI. In conclusion, our study successfully developed a combined strategy of GC-MS fingerprinting and chemical pattern recognition for the identification of HK and HI, and we also discovered chemical markers that can directly differentiate between the two species. This study can provide a foundation for the authentication of Hippocampus and holds significant importance for the conservation of wild seahorse resources.
Topics: Animals; Gas Chromatography-Mass Spectrometry; Myristic Acid; Smegmamorpha; China; Cluster Analysis; Chromatography, High Pressure Liquid; Principal Component Analysis
PubMed: 38067553
DOI: 10.3390/molecules28237824