The role of FMO3 in metabolic diseases

Flavin containing monooxygenase 3(FMO3)is a member of the flavin monooxygenase family,which can oxidize the precursor Trimethylamine(TMA)provided from food to produce Trimethylamine N-oxide(TMAO).The autosomal recessive inherited disease caused by partial functional loss of Fmo3 gene,which leads to excessive excretion of TMA in body fluids and emits fishy odor,is called Fish Odor Syndrome or Trimethylaminuria.This disease has been documented for 3,000 years ago and was first reported in the case report in 1970.FMO3 mainly exists in the liver and can participate in the TMA-TMAO metabolic balance in intestinal microorganisms,liver,and kidneys,closely related to insulin resistance,diabetes,cholesterol metabolism,and cardiovascular disease.Due to its wide range of catalytic substrates and low susceptibility to metabolite accumulation,its role in drug metabolism,new drug development,and discovery of new drug targets are increasingly valued.This review will summarize the research progress on the metabolic process and localization of FMO3,congenital genetic defects,metabolic diseases,and its related possible mechanisms.

Infrared thermography in metabolic diseases

The prevalence of metabolic diseases,some diseases that are seriously harmful for human health and affect the quality of life,is increasing year by year.Early detection and intervention is the common strategy to deal with them.Infrared thermography(IRT)is a special medical imaging technology which can capture the changes of skin temperature associated with metabolic disorders.It might be a new method for early detection of metabolic diseases.The purpose of this review is to summarize advances of the use of IRT in evaluating single metabolic disorder such as obesity,hyperglycemia and hypertension,complex metabolic disorders such as metabolic syndrome and target organ damage such as coronary artery atherosclerosis and diabetic foot.The characteristic of thermograms of metabolic disease patients,the changes of thermal maps during the development of the disease,and the lacks in current studies are also discussed in the article.

Application of medium-chain fatty acids in metabolic diseases

Medium-chain fatty acids(MCFAs),which are important dietary fats,can be rapidly metabolized to efficiently produce a high amount of energy owing to their unique transportation system.MCFAs have thus become high-value functional foods.MCFAs also have antibac-terial and immunoregulatory effects,help to maintain intestinal health,and have shown benefits for disease prevention and treatment.Therefore,they have the potential to be used for a variety of purposes.We herein describe the metabolic pathways involving MCFAs and their main biological functions in the human body.In addition,the effects of MCFAs as adjuvant therapy for different diseases,such as obesity,polycystic ovary syndrome,sarcopenia,and malignancy are summarized,and the likely mechanisms of action are discussed.Finally,we describe possible future clinical applications of MCFAs in the field of metabolic diseases.

Research Progress on Metabolic Diseases in Rural Areas

Through the review of relevant literature in recent years,it is found that the incidence rate of metabolic diseases in rural areas is on the rise:The related factors that may cause diseases include diet structure,exercise habits,medical resources and other aspects.At the same time,there are some limitations in the intervention and treatment measures of this kind of disease.It is urgent to carry out in-depth exploration for the special conditions in rural areas.By reviewing the research progress related to metabolic diseases in rural areas,more new ideas are provided for the treatment and improvement of metabolic diseases in rural areas.

Fecal microbiota transplantation in the metabolic diseases:Current status and perspectives

With the development of microbiology and metabolomics,the relationship between the intestinal microbiome and intestinal diseases has been revealed.Fecal microbiota transplantation(FMT),as a new treatment method,can affect the course of many chronic diseases such as metabolic syndrome,malignant tumor,autoimmune disease and nervous system disease.Although the mechanism of action of FMT is now well understood,there is some controversy in metabolic diseases,so its clinical application may be limited.Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection,and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases.However,the initial results are varied,suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT.The success of FMT depends on the microbial diversity and composition of donor feces.Therefore,clinical trials may fail due to the selection of ineffective donors,and not to faulty indication selection for FMT.A new understanding is that FMT not only improves insulin sensitivity,but may also alter the natural course of type 1 diabetes by modulating autoimmunity.In this review,we focus on the main mechanisms and deficiencies of FMT,and explore the optimal design of FMT research,especially in the field of cardiometabolic diseases.

Progress on haptoglobin and metabolic diseases

Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms and different phenotypes of Hp have different biological functions.Hp has antibacterial,antioxidant,and angiogenic effects and is associated with multiple diseases including simple obesity,vascular complications of diabetes mellitus,nonalcoholic fatty liver disease,hypertension,blood diseases,autoimmune diseases,and malignant tumors.Hp also participates in many life activities,indicating the importance of Hp in further studies.Previously,we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials.However,the specific mechanism of Hp in patients with simple obesity is still unclear.The purpose of this article is to introduce recent research progress on Hp,emphasizing the relationship between Hp and the development of metabolic disease,which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

The Role of CARD9 in Metabolic Diseases

Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.

Gut Microbiota and Metabolic Diseases

In this review, the characteristics of gut microbiota changes in 11 metabolic diseases, as well as the research progress on their interventions, are summarized. The gut microbiota contributes to metabolic diseases through intestinal mucosal dysfunction, chronic metabolic inflammatory response, gut brain axis imbalance, gene regulation, insulin resistance, and the action of its metabolites. The researches of cause effect relationship and mechanism are relatively few, need further study, expecting a breakthrough in the future to be a new path in the treatment of some metabolic diseases.

Research progress on the correlation between metabolic-associated fatty liver disease and metabolic diseases

Metabolic-associated fatty liver disease(MAFLD)is a positive diagnostic criterion and metabolic dysfunction is listed as an important cause of hepatic liver disease.MAFLD is a liver manifestation of metabolic syndrome and a key driver of metabolic syndrome.Glucose and lipid metabolism are disordered in MAFLD,which leads to extrahepatic complications through cytokines,genetic variation,visceral fat accumulation,dietary intake,and complex intestinal microbiome.Extensive clinical evidence suggests that MAFLD is independently associated with various metabolic diseases.With its renaming,the epidemiology,pathogenesis,and treatment of MAFLD and metabolic-related diseases need to be reassessed and studied to lay out a foundation for effective prevention and treatment strategies in the future.

Integration of multi-omics in investigations on the mechanisms of action of Chinese herbal medicine interventions in metabolic diseases

The rapid development of bioinformatics has provided novel approaches and methods for exploring the mechanisms of disease treatment via Chinese herbal medicines.Compound Chinese herbal medicines formulas have complex compositions and are characterized by their multiple constituents and diverse array of biological targets.Therefore,the mechanisms of action of most compound Chinese herbal medicines formulas cannot be adequately explained using a single pathway.Omics technologies describe high-throughput-based analytical and detection techniques,which include transcriptomics,proteomics,and metabolomics and provide multilayer parameter information that can be integrated to characterize the overall relationships involved in the therapeutic effects of Chinese herbal medicines formulas.Through their combination with network biology and drug effect networks,omics technologies also enable investigations into the mechanisms of disease treatment in traditional Chinese medicine.The integration of multiple omics technologies is in line with the concept of holism in traditional Chinese medicine and provides an approach for combining modern science and technology with traditional Chinese medicine theories.In recent years,omics technologies have been widely used to elucidate the mechanisms of action of Chinese herbal medicines.The latest studies employing multi-omics integration for investigating the mechanisms of action of Chinese herbal medicines interventions in metabolic diseases have devoted greater attention to in-depth explorations of disease pathogenesis.This paper provides a review of the following multi-omics technologies,which are used in research on the treatment of common metabolic diseases(e.g.,type-2 diabetes mellitus,nonalcoholic fatty liver disease):network pharmacology combined with metabolomics,16S rRNA sequencing combined with transcriptomics,16S rRNA sequencing combined with metabolomics,and 16S rRNA sequencing combined with network pharmacology and metabolomics.

Research progress of peroxisome proliferator-activated receptor α in metabolic diseases

Peroxisome proliferator-activated receptorα(PPAR-α)is a transcription factor activated by ligand receptors and is a subfamily of the nuclear receptor superfamily.The PPAR subfamily consists of three subtypes:PPAR-α(NR1C1),PPAR-β/δ(NR1C2)and PPAR-γ(NR1C3).Among them,PPAR-αis the first discovered transcription factor and the main regulator of fatty acid oxidation homeostasis.Some natural and synthetic ligands can activate PPAR-α,and the activation of PPAR-αthrough its ligands can modify many of the cells in the cell.Biological processes,these processes are closely related to the energy metabolism mechanism of metabolic diseases,so it represents an important molecular target for the development of new drugs for the treatment of metabolic diseases.The following summarizes the latest progress of PPAR-αand energy metabolism in terms of the structure and distribution of PPAR-α,its role in different tissues,and its role in metabolic diseases,etc.,providing a theoretical basis for the prevention and treatment of metabolic diseases.

Long noncoding RNA(lncRNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases

Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

Clinical relevance of circulating non-coding RNAs in metabolic diseases:Emphasis on obesity,diabetes,cardiovascular diseases and metabolic syndrome

Non-coding RNAs(ncRNAs)participate in the regulation of several cellular processes including transcription,RNA processing and genome rearrangement.The aberrant expression of ncRNAs is associated with several pathological conditions.In this review,we focused on recent information to elucidate the role of various regulatory ncRNAs i.e.,micro RNAs(miRNAs),circular RNAs(circRNAs)and long-chain non-coding RNAs(lncRNAs),in metabolic diseases,e.g.,obesity,diabetes mellitus(DM),cardiovascular diseases(CVD)and metabolic syndrome(MetS).The mechanisms by which ncRNAs participated in disease pathophysiology were also highlighted.miRNAs regulate the expression of genes at transcriptional and translational levels.circRNAs modulate the regulation of gene expression via miRNA sponging activity,interacting with RNA binding protein and polymerase II transcription regulation.lncRNAs regulate the expression of genes by acting as a protein decoy,miRNA sponging,miRNA host gene,binding to miRNA response elements(MRE)and the recruitment of transcriptional element or chromatin modifiers.We examined the role of ncRNAs in the disease pathogenesis and their potential role as molecular markers for diagnosis,prognosis and therapeutic targets.We showed the involvement of ncRNAs in the onset of obesity and its progression to MetS and CVD.miRNA-192,miRNA-122,and miRNA-221 were dysregulated in all these metabolic diseases.Other ncRNAs,implicated in at least three diseases include miRNA-15a,miRNA-26,miRNA-27a,miRNA-320,and miRNA-375.Dysregulation of ncRNAs increased the risk of development of DM and MetS and its progression to CVD in obese individuals.Hence,these molecules are potential targets to arrest or delay the progression of metabolic diseases.

The hippo kinases MST1/2 in cardiovascular and metabolic diseases:A promising therapeutic target option for pharmacotherapy

Cardiovascular diseases(CVDs)and metabolic disorders are major components of noncommunicable diseases,causing an enormous health and economic burden worldwide.There are common risk factors and developmental mechanisms among them,indicating the far-reaching significance in exploring the corresponding therapeutic targets.MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity.Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation.In addition,drug development against them is in full swing.In this review,we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation.Moreover,we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy,which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.

Update on the gut microbiome in health and diseases

The Human Microbiome Project,Earth Microbiome Project,and next-generation sequencing have advanced novel genome association,host genetic linkages,and pathogen identification.The microbiome is the sum of the microbes,their genetic information,and their ecological niche.This study will describe how millions of bacteria in the gut affect the human body in health and disease.The gut microbiome changes in relation with age,with an increase in Bacteroidetes and Firmicutes.Host and environmental factors affecting the gut microbiome are diet,drugs,age,smoking,exercise,and host genetics.In addition,changes in the gut microbiome may affect the local gut immune system and systemic immune system.In this study,we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases.Due to the high number of publications on the argument,from a methodologically point of view,we decided to select the best papers published in referred journals in the last 3 years.Then we selected the previously published papers.The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases

Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.

Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

Recent advances in age-related metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease(MASLD)affects approximately 25%of the world's population and has become a leading cause of chronic liver disease.In recent years,an increasing amount of data suggests that MASLD is associated with aging.As the population ages,age-related MASLD will become a major global health problem.Targeting an aging will become a new approach to the treatment of MASLD.This paper reviews the current studies on the role of aging-related factors and therapeutic targets in MASLD,including:Oxidative stress,autophagy,mitochondrial homeostasis,bile acid metabolism homeostasis,and dysbiosis.The aim is to identify effective therapeutic targets for age-related MASLD and its progression.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.