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Cardio‐cerebrovascular diseases encompass pathological changes in the heart, brain and vascular system, which pose a great threat to health and well‐being worldwide. Moreover, metabolic diseases contribute to and exacerbate the impact of vascular diseases. Inflammation is a complex process that protects against noxious stimuli but is also dysregulated in numerous so‐called inflammatory diseases, one of which is atherosclerosis. Inflammation involves multiple organ systems and a complex cascade of molecular and cellular events. Numerous studies have shown that inflammation plays a vital role in cardio‐cerebrovascular diseases and metabolic diseases. The absent in melanoma 2 (AIM2) inflammasome detects and is subsequently activated by double‐stranded DNA in damaged cells and pathogens. With the assistance of the mature effector molecule caspase‐1, the AIM2 inflammasome performs crucial biological functions that underpin its involvement in cardio‐cerebrovascular diseases and related metabolic diseases: The production of interleukin‐1 beta (IL-1β), interleukin‐18 (IL-18) and N‐terminal pore‐forming Gasdermin D fragment (GSDMD‐N) mediates a series of inflammatory responses and programmed cell death (pyroptosis and PANoptosis). Currently, several agents have been reported to inhibit the activity of the AIM2 inflammasome and have the potential to be evaluated for use in clinical settings. In this review, we systemically elucidate the assembly, biological functions, regulation and mechanisms of the AIM2 inflammasome in cardio‐cerebrovascular diseases and related metabolic diseases and outline the inhibitory agents of the AIM2 inflammasome as potential therapeutic drugs. [ABSTRACT FROM AUTHOR]

The gut microbiota plays an important role in maintaining human health and in the pathogenesis of several diseases. Antibiotics are among the most commonly prescribed drugs and have a significant impact on the structure and function of the gut microbiota. The understanding that a healthy gut microbiota prevents the development of many diseases has also led to its consideration as a potential therapeutic target. At the same time, any factor that alters the gut microbiota becomes important in this approach. Exercise and antibacterial therapy have a direct effect on the microbiota. The review reflects the current state of publications on the mechanisms of intestinal bacterial involvement in the pathogenesis of cardiovascular, metabolic, and neurodegenerative diseases. The physiological mechanisms of the influence of physical activity on the composition of the gut microbiota are considered. The mechanisms of the common interface between exercise and antibacterial therapy will be considered using the example of several socially important diseases. The aim of the study is to show the physiological relationship between the effects of exercise and antibiotics on the gut microbiota. [ABSTRACT FROM AUTHOR]

Summary: Chronic inflammation of adipose tissue is a prominent characteristic of many metabolic diseases. Lipid metabolism in adipose tissue is consistently dysregulated during inflammation, which is characterized by substantial infiltration by proinflammatory cells and high cytokine concentrations. Adipose tissue inflammation is caused by a variety of endogenous factors, such as mitochondrial dysfunction, reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, cellular senescence, ceramides biosynthesis and mediators of lipopolysaccharides (LPS) signaling. Additionally, the gut microbiota also plays a crucial role in regulating adipose tissue inflammation. Essentially, adipose tissue inflammation arises from an imbalance in adipocyte metabolism and the regulation of immune cells. Specific inflammatory signals, including nuclear factor‐κB (NF‐κB) signaling, inflammasome signaling and inflammation‐mediated autophagy, have been shown to be involved in the metabolic regulation. The pathogenesis of metabolic diseases characterized by chronic inflammation (obesity, insulin resistance, atherosclerosis and nonalcoholic fatty liver disease [NAFLD]) and recent research regarding potential therapeutic targets for these conditions are also discussed in this review. [ABSTRACT FROM AUTHOR]

While FXR has shown promise in regulating bile acid synthesis and maintaining glucose and lipid homeostasis, undesired side effects have been observed in clinical trials. To address this issue, the development of intestinally restricted FXR modulators has gained attention as a new avenue for drug design with the potential for safer systematic effects. Our review examines all currently known intestinally restricted FXR ligands and provides insights into the steps taken to enhance intestinal selectivity. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as Alzheimer's disease (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways. Here, we specifically highlight ABC transporters involved in the maintenance of brain homeostasis and their implications in its metabolic regulation. We also show new aspects related to ABC transporter function found in less recognized diseases, such as Huntington's disease (HD) and experimental autoimmune encephalomyelitis (EAE), as a model for multiple sclerosis (MS). Understanding both their impact on the physiological regulation of the CNS and their roles in brain diseases holds promise for uncovering new therapeutic options. Further investigations and preclinical studies are warranted to elucidate the complex interplay between glial ABC transporters and physiological brain functions, potentially leading to effective therapeutic interventions also for rare CNS disorders. [ABSTRACT FROM AUTHOR]

Background: Inherited metabolic disorders (IEMs) can be represented in children and adolescents by psychiatric disorders. The early diagnosis of IEMs is crucial for clinical outcome and treatment. The aim of this review is to analyze the most recurrent and specific psychiatric features related to IEMs in pediatrics, based on the onset type and psychiatric phenotypes. Methods: Following the PRISMA Statement, a systematic literature review was performed using a predefined algorithm to find suitable publications in scientific databases of interest. After removing duplicates and screening titles and abstracts, suitable papers were analyzed and screened for inclusion and exclusion criteria. Finally, the data of interest were retrieved from the remaining articles. Results: The results of this study are reported by type of symptoms onset (acute and chronic) and by possible psychiatric features related to IEMs. Psychiatric phenomenology has been grouped into five main clinical manifestations: mood and anxiety disorders; schizophrenia-spectrum disorders; catatonia; eating disorders; and self-injurious behaviors. Conclusions: The inclusion of a variety of psychiatric manifestations in children and adolescents with different IEMs is a key strength of this study, which allowed us to explore the facets of seemingly different disorders in depth, avoiding possible misdiagnoses, with the related delay of early and appropriate treatments. [ABSTRACT FROM AUTHOR]

Summary ChatGPT/GPT‐4 is a conversational large language model (LLM) based on artificial intelligence (AI). The potential application of LLM as a virtual assistant for bariatric healthcare professionals in education and practice may be promising if relevant and valid issues are actively examined and addressed. In general medical terms, it is possible that AI models like ChatGPT/GPT‐4 will be deeply integrated into medical scenarios, improving medical efficiency and quality, and allowing doctors more time to communicate with patients and implement personalized health management. Chatbots based on AI have great potential in bariatric healthcare and may play an important role in predicting and intervening in weight loss and obesity‐related complications. However, given its potential limitations, we should carefully consider the medical, legal, ethical, data security, privacy, and liability issues arising from medical errors caused by ChatGPT/GPT‐4. This concern also extends to ChatGPT/GPT ‐4's ability to justify wrong decisions, and there is an urgent need for appropriate guidelines and regulations to ensure the safe and responsible use of ChatGPT/GPT‐4. [ABSTRACT FROM AUTHOR]

[Display omitted] • Our study explored the causal association between 42 predominant risk factors and erectile dysfunction (ED) under a two-sample MR framework. • This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG and adiponectin in the onset and development of ED. A clear causal link may be beneficial to early identification and target intervention in patients with ED. • No significant association was detected between lipid levels and ED. • Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels can decrease the risk of ED. • Identifying reversible risk factors is the first-line evaluation for ED patients as per the diagnostic work-up of the European Association of Urology Guidelines. This study provides a better understanding of the risk factors of ED and is conducive to early identification and intervention of ED. The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED. Univariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings. Genetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P < 0.05). Additionally, genetic liability to higher body fat percentage and alcohol consumption were suggestively associated with an increased risk of ED (P < 0.05 and adjusted P > 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P < 0.05). No significant association was detected between lipid levels and ED. Multivariate MR identified type 2 diabetes, basal metabolic rate, cigarette consumption, hypertension, and coronary heart disease as risk factors for ED. The combined results confirmed that waist circumference, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, snoring, hypertension, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder could increase the risk of ED (all P < 0.05), while higher SHBG decreased the risk of ED (P = 0.004). There were suggestive significances of BMI, insomnia, and stroke on ED (P < 0.05 and adjusted P > 0.05). This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED. [ABSTRACT FROM AUTHOR]

Myeloid-derived growth factor (MYDGF) is a paracrine protein produced by bone marrow-derived monocytes and macrophages. Current research shows that it has protective effects on the cardiovascular system, such as repairing heart tissue after myocardial infarction, enhancing cardiomyocyte proliferation, improving cardiac regeneration after myocardial injury, regulating proliferation and survival of endothelial cells, reducing endothelial cell damage, resisting pressure overload-induced heart failure, as well as protecting against atherosclerosis. Furthermore, regarding the metabolic diseases, MYDGF has effects of improving type 2 diabetes mellitus, relieving non-alcoholic fatty liver disease, alleviating glomerular diseases, and resisting osteoporosis. Herein, we will discuss the biology of MYDGF and its effects on cardiovascular and metabolic diseases. [Display omitted] • MYDGF is a paracrine protein produced by bone marrow-derived monocytes and macrophages. • MYDGF is an endoplasmic reticulum-resident protein. • MYDGF has great potential as a biomarker for CVMD diagnosis and prognosis. • MYDGF is a potential therapeutic target for CVMD. [ABSTRACT FROM AUTHOR]

The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or "leaky gut", has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes. [ABSTRACT FROM AUTHOR]

The prevalence of overweight, obesity, and related metabolic diseases increase year by year, which has become an urgent global public health problem. At present, a series of prevention and control measures and programs have been formulated and implemented worldwide, but the current situation has not been effectively controlled. However, the diagnostic criteria of overweight and obesity are still not uniform in various countries and regions, which also brings great challenges to solve this problem. Therefore, this paper interprets the identification and assessment of overweight and obesity in children, adolescents and adults in NICE′s Obesity:Identification, Assessment and Management in 2023, in order to provide a simple reference for the comprehensive evaluation of overweight and obesity. [ABSTRACT FROM AUTHOR]

Metabolic diseases affect many people in Indonesia. Risk factors for metabolic diseases include age, lack of physical activity, poor diet, and heredity. To provide insight to the community, including youth cadres, is one of the most important efforts to prevent metabolic diseases. The method used in our program was to provide health education to youth cadres in Sagaracipta village, Ciparay subdistrict, Bandung district, regarding how to prevent metabolic disease through home visit, seminars, and counseling training. During the home visit activities, 16 residents' houses were visited to become learning media for youth cadres. The comparison of pre-test and post-test scores from 17 youth cadres in the seminar showed good improvement (39%) of their knowledge regarding metabolic diseases. At the end of the counseling training, 78.13% of youth cadres understood how to provide counseling about metabolic disease to the community. [ABSTRACT FROM AUTHOR]

Background and Aim The advantages of omega-3 fatty acid, which is one of the polyunsaturated fatty acids (PUFA), for health are the subjects of an increasing number of studies. Omega-3 may help prevent or treat obesity and related metabolic illnesses, according to studies conducted both on mice and people. This study aims to survey the benefits of omega-3 in type 2 diabetes mellitus. Methods Online databases PubMed, Google Scholar, and Science Direct were searched for articles discussing omega-3 fatty acid and diabetic patients in the recent five years (2017-2023). Results Recent research has shown the value of omega-3 fatty acid supplements, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in the treatment of several disorders. Omega-3 fatty acids have beneficial effects on glycemic control and insulin resistance in patients with type 2 diabetes mellitus. Conclusions Clinical studies have demonstrated that omega-3 fatty acids may assist in controlling type 2 diabetes mellitus and reducing obesity and related metabolic diseases. [ABSTRACT FROM AUTHOR]

Glycation is a physiological process that determines the aging of the organism, while in states of metabolic disorders it is significantly intensified. High concentrations of compounds such as reducing sugars or reactive aldehydes derived from lipid oxidation, occurring for example in diabetes, atherosclerosis, dyslipidemia, obesity or metabolic syndrome, lead to increased glycation of proteins, lipids and nucleic acids. The level of advanced glycation end-products (AGEs) in the body depends on rapidity of their production and the rate of their removal by the urinary system. AGEs, accumulated in the extracellular matrix of the blood vessels and other organs, cause irreversible changes in the biochemical and biomechanical properties of tissues. As a consequence, micro- and macroangiopathies appear in the system, and may contribute to the organ failure, like kidneys and heart. Elevated levels of AGEs also increase the risk of Alzheimer's disease and various cancers. In this paper, we propose a new classification due to modified amino acid residues: arginyl-AGEs, monolysyl-AGEs and lysyl-arginyl-AGEs and dilysyl-AGEs. Furthermore, we describe in detail the effect of AGEs on the pathogenesis of metabolic and old age diseases, such as diabetic complications, atherosclerosis and neurodegenerative diseases. We summarize the currently available data on the diagnostic value of AGEs and present the AGEs as a therapeutic goal in a wide range of medical problems, including SARS-CoV-2 infection and so-called long COVID. [ABSTRACT FROM AUTHOR]

Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m² ) and males with evidence of MetDys (n=14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion: These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease. [ABSTRACT FROM AUTHOR]

Low-grade chronic inflammation and adipocyte dysfunction are prominent risk factors of insulin resistance and type 2 diabetes mellitus (T2DM) in obesity. Thus, prevention of inflammation and adipocyte dysfunction could be one possible approach to mitigate T2DM development. Several Ficus species have been used in traditional medicine for ameliorating inflammation and T2DM. Our previous studies reported biological effects of Ficus lindsayana including antioxidant, anti-cancer, and anti-α-glucosidase activities. Further, this study therefore investigated whether F. lindsayana latex (FLLE) and root (FLRE) extracts inhibit inflammation-stimulated insulin resistance in adipocytes and inflammation in macrophages. FLLE and FLRE (200 µg/mL) had no significant cytotoxicity for macrophages, adipocytes, and blood cells (PBMCs and RBCs). FLRE had a total flavonoid content about three times higher than FLLE, while both had similar levels of total phenolic content. FLRE showed higher abilities than FLLE in suppressing inflammation in both macrophages and adipocytes and reversing the inflammation-induced insulin resistance in adipocytes. In TNF-α-induced adipocytes, FLRE significantly improved insulin-induced glucose uptake and insulin-suppressed lipolysis, while FLLE only significantly improved glucose uptake. Moreover, FLRE and FLLE remarkably reduced chemoattractant (MCP-1) but improved adipogenic (PPARγ and CEBPα) gene expression, leading to the promotion of adipogenesis and the suppression of insulin resistance. In LPS-induced macrophages, FLRE, but not FLLE, significantly inhibited LPS-induced NO production. Moreover, FLRE significantly reduced LPS-stimulated iNOS, COX-2, IL-1β, IL-6, and TNF-α gene expression. These results may provide the potential data for the development of this plant, especially the root part, as an alternative medicine, functional ingredient, or food supplement for the prevention of inflammation and obesity-associated insulin resistance, as well as T2DM. [ABSTRACT FROM AUTHOR]

Metabolic diseases have become a major threat to human health worldwide as a result of changing lifestyles. The exploration of the underlying molecular mechanisms of metabolic diseases and the development of improved therapeutic methods have been hindered by the lack of appropriate human experimental models. Organoids are three‐dimensional in vitro models of self‐renewing cells that spontaneously self‐organize into structures similar to the corresponding in vivo tissues, recapitulating the original tissue function. Off‐body organoid technology has been successfully applied to disease modelling, developmental biology, regenerative medicine, and tumour precision medicine. This new generation of biological models has received widespread attention. This article focuses on the construction process and research progress with regard to organoids related to metabolic diseases in recent years, and looks forward to their prospective applications. [ABSTRACT FROM AUTHOR]

Receiving information in the case of a positive or false-positive expanded newborn screening (ENBS) result for metabolic diseases is a stressful event. The availability of psychological support to families is crucial across the different communication steps and is recommended by different guidelines and position papers. However, more information is needed about the availability of psychological resources in the ENBS process. This national survey aimed to provide an overview of the availability of psychological resources for parents who received communication of positivity at the ENBS in the 23 Italian centers and how the support is provided to parents. An online survey was sent to the Heads of the ENBS centers asking about the availability of a clinical psychologist, their involvement in the ENBS process, and an estimation of parents receiving psychological support. More than 60% of the centers report having a clinical psychologist in the ENBS team; however, in more than 50% of cases, the psychologist does not participate in the consultation with parents (nor for the first consultation post-positivity or at confirmation of diagnosis). Furthermore, nearly 60% of the centers reported the experience of parental rejection of psychological sessions. Conclusion: There is a need for harmonization among the Italian ENBS centers concerning the availability of psychological resources and how these resources are provided to families. Parents' needs remained only partially fulfilled. What is Known: • Receiving communication of positivity at the ENBS can be highly stressful for parents and requires adequate psychological support. • The guidelines recommend psychological support for parents during the ENBS process. What is New: • Only 14/23 (60.9%) of Italian ENBS centers have a clinical psychologist within the team. • In half of the consultations with parents receiving communication of positivity, the clinical psychologist is never involved. [ABSTRACT FROM AUTHOR]

Thyroid hormone metabolites, as important regulators of physiology and pathology, have received more and more attention. In addition to having similar effects to thyroid hormones in modulating hyperglycemia, improving dyslipidemia and promoting brain development, researchers have also found that they play an important role in protecting the heart from myocardial ischemia reperfusion injury and inhibiting the proliferation of tumor cells. Further investigations of thyroid hormone metabolites are needed to fully reveal their physiological actions and mechanisms, and this may open new perspectives for the treatment of metabolic diseases, neurological diseases and cancer. [ABSTRACT FROM AUTHOR]

Metabolic diseases refers to a type of disease caused by abnormal material metabolism or energy metabolism in the body. The immune inflammatory response mediated by metabolic factors takes a long time and can cause serious damage to the physiological functions of the corresponding tissues. The NLRP3 inflammasome is a multimeric cytosolic protein complex that can recognize a variety of pathogens and dangerous damage signals inside and outside the cell to cause the activation of caspase-1, which promotes maturation and release of the inflammatory cytokines IL-1β and IL-18. In this review, we will cover the mechanisms of NLRP3 inflammasome activation and its divergent roles in the pathogenesis of inflammation-associated diseases such as diabetes, obesity, gout, atherosclerosis, hypertension disease, highlighting the therapeutic potential of targeting this pathway, aiming to provide a basis for further research. [ABSTRACT FROM AUTHOR]

Lifecourse nutrition encompasses nourishment from early development into parenthood. From preconception and pregnancy to childhood, late adolescence, and reproductive years, life course nutrition explores links between dietary exposures and health outcomes in current and future generations from a public health perspective, usually addressing lifestyle behaviours, reproductive well-being and maternal-child health strategies. However, nutritional factors that play a role in conceiving and sustaining new life might also require a molecular perspective and recognition of critical interactions between specific nutrients and relevant biochemical pathways. The present perspective summarises evidence about the links between diet during periconception and next-generation health and outlines the main metabolic networks involved in nutritional biology of this sensitive time frame. [ABSTRACT FROM AUTHOR]

Various tubers and rhizomes of local plant species in Indonesia have potential as alternative foods and resources of dietary fiber that could counteract metabolic diseases, including obesity, diabetes, and associated health issues. However, studies focusing on the composition and medicinal benefits of extracted fibers from tubers and rhizomes remain limited. Our present study aimed to explore the composition and the beneficial effects of dietary fiber extracted from tubers of achira (Canna edulis), Mentawai taro (Colocasia sp.), arrowroot (Maranta arundinacea), and jicama (Pachyrhizus erosus) to counteract obesity development in mice fed with a fatty diet. Fibers were extracted from tubers and rhizomes, followed by proximate analysis to determine the nutritional and fiber composition. Thereafter, each fiber was tested for its effectiveness in preventing obesity caused by a high-fat diet (HFD) by using mice as the animal model. We revealed that all extracted fibers predominantly consisted of non-starchy carbs with very low fat and protein levels. The extract of achira and jicama consisted of higher total dietary fiber as compared to others. Our experiment on mice demonstrated that supplementation of 25% fiber of achira, Mentawai taro, arrowroot, and jicama in HFD could effectively prevent obesity independent of daily calorie intake. Our findings suggest that the dietary fiber of achira, Mentawai taro, arrowroot, and jicama could be a potent candidate as a supplement to combat HFD-induced obesity. [ABSTRACT FROM AUTHOR]

Human gut microbiota is rich and diverse, among which gut microbiota can affect host metabolism, immunity and other processes through the brain -gut axis pathway, and then is related to the occurrence and development of a variety of diseases. The changes of intestinal flora in patients with polycystic ovary syndrome (PCOS) are related to clinical features and complications such as insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome. Recent studies have shown that intestinal flora may also affect the pathogenesis and pathological process of PCOS through intestinal metabolites such as bile acids, short-chain fatty acids, ceramides and trimethylamine derivatives. In addition, some studies have explored the application of fecal microbiota transplantation, supplementation of probiotics and synbiotics to regulate intestinal flora, in order to provide a theoretical basis for improving the clinical manifestations and related complications of PCOS. [ABSTRACT FROM AUTHOR]

Metabolic disorders, characterized by a complex pathogenesis, are experiencing a rising prevalence globally and a trend toward younger populations, making them a significant public health concern. Olfaction, a crucial sensory function, plays a pivotal role in an individual′s nutrition and quality of life. There is a bidirectional relationship between obesity and olfactory function. Olfaction is influenced by nutritional status; simultaneously, it plays a vital role in the regulation of food intake, energy expenditure, and lipid metabolism. Moreover, individuals with metabolic disorders such as type 2 diabetes and obstructive sleep apnea syndrome exhibit olfactory dysfunction. Mechanisms underlying olfactory changes in metabolic disorders involve alterations in metabolic states such as hyperglycemia and insulin resistance. These changes can lead to dysregulation of peptide hormones, adipocyte factors, and neurotransmitters, which may potentially act as mediators between metabolic disorders and olfactory dysfunction. Vascular and neural alterations resulting from metabolic disorders can directly damage olfactory nerves or induce abnormal neural transmission. Furthermore, dysbiosis in the gut microbiota induced by metabolic disorders is a potential mechanism for olfactory dysfunction. Cognitive dysfunction is a significant complication of metabolic disorders. Olfactory dysfunction can serve as an early clinical manifestation of cognitive impairment and contributes to early identification and assessment of diseases. This article reviews recent researches on the relationship between metabolic diseases and olfactory changes and the potential mechanisms. [ABSTRACT FROM AUTHOR]

Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life. [ABSTRACT FROM AUTHOR]

One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributes significantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T‐cells, B‐cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1C metabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases. Significance statement: One‐carbon (1C) metabolism is critical for cellular biochemical properties and physiology.A malfunction of 1C metabolism disrupts immune cell functions implicated in disease pathology.Recent studies are exploiting the re‐wiring of 1C metabolism for therapeutic interventions for chronic diseases. [ABSTRACT FROM AUTHOR]

Metabolic disorders present a significant public health challenge globally. The intricate relationship between the gut microbiome, particularly Bacteroides spp. (BAC), and obesity, including their specific metabolic functions, remains partly unresolved. This review consolidates current research on BAC's role in obesity and lipid metabolism, with three objectives: (1) To summarize the gut microbiota's impact on obesity; (2) To assess BAC's efficacy in obesity intervention; (3) To explore BAC's mechanisms in obesity and lipid metabolism management. This review critically examines the role of BAC in obesity, integrating findings from clinical and preclinical studies. We highlight the changes in BAC diversity and concentration following successful obesity treatment and discuss the notable differences in BAC characteristics among individuals with varying obesity levels. Furthermore, we review recent preclinical studies demonstrating the potential of BAC in ameliorating obesity and related inflammatory conditions, providing detailed insights into the methodologies of these in vivo experiments. Additionally, certain BAC-derived metabolites have been shown to be involved in the regulation of host lipid metabolism-related pathways. The enhanced TNF production by dendritic cells following BAC administration, in response to LPS, also positions BAC as a potential adjunctive therapy in obesity management. [ABSTRACT FROM AUTHOR]

Metabolic diseases are prevalent in modern society and have reached pandemic proportions. Metabolic diseases have systemic effects on the body and can lead to changes in the neuroendocrine stress axis, the critical regulator of the body's stress response. These changes may be attributed to rising insulin levels and the release of adipokines and inflammatory cytokines by adipose tissue, which affect hormone production by the neuroendocrine stress axis. Chronic stress due to inflammation may exacerbate these effects. The increased sensitivity of the neuroendocrine stress axis may be responsible for the development of metabolic syndrome, providing a possible explanation for the high prevalence of severe comorbidities such as heart disease and stroke associated with metabolic disease. In this review, we address current knowledge of the neuroendocrine stress axis in response to metabolic disease and discuss its role in developing metabolic syndrome. [ABSTRACT FROM AUTHOR]

LECT2 is not a routine diagnostic marker for any disease, but it has been associated with many pathologies, including systemic amyloidosis, rheumatoid arthritis, diabetes, atherosclerosis, and metabolic syndrome. With human aortic sections (n = 22) and sera from geriatric subjects (n = 79), we analyzed the relationships that could be observed between this protein and other parameters related to metabolic diseases. As a result, we observed a relatively high (r~0.8, p < 0.05) positive correlation between SRA and LECT2 and a negative correlation between EGFR and LECT2 (r~−0.4, p < 0.05). We observed LECT2 expression in macrophages, myocytes, and other aortic cells, with a tendency to be overexpressed in developed atherosclerotic plaques. We conclude that LECT2 exerts its chemotactic effects not only as a protein synthesized in the liver and secreted and circulating in the blood but also as a locally expressed protein within atherosclerotic plaque development. The LECT2-EGFR correlation suggests an association of this protein with loss of normal renal function. This fact can be associated with LECT2 amyloidosis, although it should be verified whether in the geriatric population there is indeed a widespread accumulation of LECT2 with the progression of aging or whether it is rather a marker of general deterioration of renal function. [ABSTRACT FROM AUTHOR]

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuate their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response. [ABSTRACT FROM AUTHOR]

Inborn errors of metabolism (IEMs) are inherited biochemical/metabolic disorders that are commonly present in the immediate neonatal period. The aim of this retrospective study was to determine the incidence and distribution of IEMs in newborn infants delivered in our hospital and to evaluate its outcome. A total of 16 494 (99.9%) newborn infants were screened for IEMs. We found 29 newborn infants diagnosed with IEMs, representing an incidence of 1 per ~569 live births and a cumulative incidence of 176 per 100 000 live births of the IEM-positive newborn infants. We detected 11 different types of IEMs, and the top 6 categories were endocrinopathies followed by carbohydrates disorders, vitamin-responsive disorders, organic acid defects, and ketogenesis and ketolysis defects. This study does reflect upon the importance of educating the general population about the perils of Consanguineous Marriages (CMs) in order to reduce related disorders significantly, especially in families who have a history of IEMs. [ABSTRACT FROM AUTHOR]

Quality of life, well-being, and psycho-emotional balance are closely related to the quality of the diet, the level of physical activity, the quality of rest, but also the absence of the consumption of narcotic substances and tobacco, or alcohol abuse. Based on the distribution of a questionnaire that included 30 questions, we aimed to statistically evaluate several factors that influence mental health and vices. It recorded a total of 1719 valid responses, which came from 78.3% female respondents and 21.7% male respondents. After processing the anthropometric data, it was observed that the majority of respondents are of normal weight (63.87%) and come from women in particular (36.13%). Based on the answers recorded, although over 60% of the respondents participating in the study are up to 40 years old, there is an increased tendency towards sedentarism (over 58% of the respondents declaring that they do sports very rarely or not at all), a low tendency regarding optimal consumption of vegetables and fruits, many respondents do not hydrate properly, which is why approximately 60% of respondents feel frequently tired, and over 32% are frequently nervous. The increased level of stress among the respondents and emotional eating are also generated by inadequate rest, reduced physical activity, and a diet that does not help the efficient detoxification of the body. [ABSTRACT FROM AUTHOR]

Naturally derived alkaloids belong to a class of quite significant organic compounds. Coptisine, a benzyl tetrahydroisoquinoline alkaloid, is one of the major bioactive constituents in Coptis chinensis Franch., which is a famous traditional Chinese medicine. C. chinensis possesses many kinds of functions, including the ability to eliminate heat, expel dampness, purge fire, and remove noxious substances. In Asian countries, C. chinensis is traditionally employed to treat carbuncle and furuncle, diabetes, jaundice, stomach and intestinal disorders, red eyes, toothache, and skin disorders. Up to now, there has been plenty of research of coptisine with respect to its pharmacology. Nevertheless, a comprehensive review of coptisine-associated research is urgently needed. This paper was designed to summarize in detail the progress in the research of the pharmacology, pharmacokinetics, safety, and formulation of coptisine. The related studies included in this paper were retrieved from the following academic databases: The Web of Science, PubMed, Google scholar, Elsevier, and CNKI. The cutoff date was January 2023. Coptisine manifests various pharmacological actions, including anticancer, antimetabolic disease, anti-inflammatory disease, and antigastrointestinal disease effects, among others. Based on its pharmacokinetics, the primary metabolic site of coptisine is the liver. Coptisine is poorly absorbed in the gastrointestinal system, and most of it is expelled in the form of its prototype through feces. Regarding safety, coptisine displayed potential hepatotoxicity. Some novel formulations, including the β -cyclodextrin-based inclusion complex and nanocarriers, could effectively enhance the bioavailability of coptisine. The traditional use of C. chinensis is closely connected with the pharmacological actions of coptisine. Although there are some disadvantages, including poor solubility, low bioavailability, and possible hepatotoxicity, coptisine is still a prospective naturally derived drug candidate, especially in the treatment of tumors as well as metabolic and inflammatory diseases. Further investigation of coptisine is necessary to facilitate the application of coptisine-based drugs in clinical practice. [ABSTRACT FROM AUTHOR]

Brazil has several important biomes holding impressive fauna and flora biodiversity. Cerrado being one of the richest ones and a significant area in the search for new plant-based products, such as foods, cosmetics, and medicines. The therapeutic potential of Cerrado plants has been described by several studies associating ethnopharmacological knowledge with phytochemical compounds and therapeutic effects. Based on this wide range of options, the Brazilian population has been using these medicinal plants (MP) for centuries for the treatment of various health conditions. Among these, we highlight metabolic diseases, namely obesity and its metabolic alterations from metabolic syndrome to later stages such as type 2 diabetes (T2D). Several studies have shown that adipose tissue (AT) dysfunction leads to proinflammatory cytokine secretion and impaired free fatty acid (FFA) oxidation and oxidative status, creating the basis for insulin resistance and glucose dysmetabolism. In this scenario, the great Brazilian biodiversity and a wide variety of phytochemical compounds make it an important candidate for the identification of pharmacological strategies for the treatment of these conditions. This review aimed to analyze and summarize the current literature on plants from the Brazilian Cerrado that have therapeutic activity against obesity and its metabolic conditions, reducing inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to analyze the cross‐sectional and longitudinal association of physical activity (PA) levels and PA patterns with metabolic syndrome score (MetS) in children and adolescents. Methods: A total of 175 children (82 females) and 188 adolescents (95 females) were included. Objective PA levels and patterns were determined by accelerometry. MetS was computed from waist circumference, systolic blood pressure, triglycerides, high‐density lipoprotein cholesterol, and glucose levels. Different linear regression models were implemented to examine the associations of PA with MetS. Results: Vigorous PA, moderate‐vigorous PA, number of bouts per day in 10 min (N10), and total time in bouts per day in 10 min (T10) were negatively associated with MetS in male children and adolescents at cross‐sectional level (β ranging from −0.005 to −0.164, all p < 0.05). Total time in bouts per day in 20 min in male children, and vigorous PA and N10 in female children were longitudinally and negatively associated with MetS (β ranging from −0.011 to −0.247, all p < 0.05). Conclusions: Associations of PA and MetS were observed at cross‐sectional level in males and longitudinally in female children. The associations in PA patterns were found when patterns were grouped into bouts of 10 min. Therefore, for future studies of PA with health markers in the pediatric population, it would be advisable to choose bouts of shorter duration. [ABSTRACT FROM AUTHOR]

Ketosis is a disease that affects high-yielding dairy cattle during the peripartum period, causing clinical and metabolic alterations, and significant productive and economic losses. This study aimed to report three cases of clinical ketosis in dairy cows. The three animals of the Holstein breed, reared in a semi-intensive regime, with a history of 40-45 days postpartum, showed signs of apathy, lack of appetite and drop in milk production. After clinical examination and complementary tests, one case of primary clinical ketosis and two cases of clinical ketosis secondary to left displaced abomasum or anaplasmosis were diagnosed. The animals presented hyperketonemia, ketonuria and normo or hypoglycemia, which were determined by rapid tests. Treatment was instituted with a view to reducing ketogenesis, restoring blood glucose and resolving concomitant diseases, with full clinical and productive recovery. The reports of these cases reinforce the importance of knowing the disease, highlighting the use of rapid tests for the field diagnosis of ketosis, enabling early and accurate treatment, thus contributing to the reduction of damage associated with its occurrence. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the clinical spectrum of metabolic storage disorders presenting to a public sector tertiary care hospital in Karachi, Pakistan. METHODOLOGY: This retrospective, cross-sectional study was conducted at the Department of Pediatrics, Dr. Ruth K.M Pfau Civil Hospital Karachi, in 2021. We reviewed the medical records of patients from January 2015 to December 2020. We included all pediatric patients admitted with suspicion of metabolic storage disorders based on two or more: visceromegaly, developmental delay, regression of milestones, fits without fever, family history of similar illness, and family history of expiry of children due to unknown reasons. Patients of malaria, enteric fever, epilepsy and cerebral palsy were excluded. We noted the demographic and clinical variables and applied descriptive statistics using SPSS version 22. RESULTS: Out of n=140 suspected children, n=40 (28.5%) patients were diagnosed with metabolic storage disorder. Among these, 26 (65%) were Lysosomal, and 14 (35%) were Glycogen storage disorders (LSDs and GSDs). The most common clinical feature of LSDs was faltering growth in 23 (88.4%), while for GSDs, it was abdominal distention and hepatomegaly in 100% of patients. Mucopolysaccharidoses were the most common type of LSD identified in 9 (34.6%). Interestingly, family history of similar illness was not a standard feature (19.2% for LSDs and 7% for GSDs). CONCLUSION: Metabolic storage disorders are an emerging concern to pediatric health in our population. Physicians need to keep a high index of suspicion for patients with faltering growth and visceromegaly, with or without a significant family history. [ABSTRACT FROM AUTHOR]

Introduction: Hyponatremia is one of the most common electrolyte disturbances encountered in medical wards, occurring in up to 22% of hospitalised patients. Timely recognition and correction of hyponatremia in hospitalised patients may help decrease in-hospital mortality and symptom severity, reduce the need for intensive hospital care, decrease the duration of hospitalisation and associated costs, and improve the treatment of underlying co-morbid conditions and patient's quality of life. Aim: To compare the clinical presentation, aetiology, biochemical profile, management strategies, and outcomes of hyponatremia in geriatric and non-geriatric individuals admitted to a tertiary care centre. Materials and Methods: This prospective cohort study was conducted in the Department of General Medicine at Mahatma Gandhi Medical College and Research Institute, Pondicherry, India, from March 2021 to September 2022. A total of 166 subjects (83 geriatric and 83 non-geriatric patients) receiving inpatient services with hyponatremia were enrolled in the study by consecutive sampling. Patients over 18 years of age admitted to the Department of General Medicine with serum sodium levels below 135 mEq/L were included. Comparison of both the groups were done based on clinical presentation, laboratory values, co-morbidities, prescription drugs taken, aetiology, treatment given, and outcomes. For quantitative variables, mean, standard deviation, and independent t-tests were used, while percentages were used for qualitative variables. Results: The majority of subjects in the non-geriatric group belonged to the age group of 50-59 years, with a mean age of 50.7 years. In the geriatric group, most subjects were in the age group of 65-74 years, with a mean age of 74.5 years. The most common cause of hyponatremia in both groups was Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), with 32 (38.6%) cases in the non-geriatric group and 27 (32.5%) cases in the geriatric group. This was followed by volume overload in the non-geriatric group, with 14 (16.9%) cases, and drug-induced hyponatremia in the geriatric group, with 22 (26.5%) cases. The most common drug causing hyponatremia was furosemide in both groups. In non-geriatric patients, the most common symptom was giddiness, with 28 (34.1%) cases, while in geriatric patients, it was nausea/vomiting, with 25 (30.1%) cases. Tolvaptan was the most common treatment used in both groups, with 12 (92.3%) of patients with mild hyponatremia receiving it in the non-geriatric group (p=0.042), and 46 (55.4%) patients in the geriatric group, with most of them having moderate hyponatremia (26, 86.7%, p<0.001). Conclusion: The results of the non-geriatric and geriatric groups were similar in terms of clinical presentation, biochemical parameters, management strategies, and outcome of hyponatremia. However, the aetiology of hyponatremia appeared to be different. The most common cause of hyponatremia was SIADH in both groups, followed by volume overload in the non-geriatric group and drug-induced hyponatremia in the geriatric group. [ABSTRACT FROM AUTHOR]

The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-β in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-β agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-β agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-β agonists have on hepatic lipid metabolism. [ABSTRACT FROM AUTHOR]

Purpose: To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities. Methods: We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression. Results: During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30–40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD. Conclusions: FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30–40 and female populations above 60 for FLD prevention and treatment. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are among the leading causes of death worldwide. Many lines of evidence suggest that the disturbances in circadian rhythm are responsible for the development of CVDs; however, circadian misalignment is not yet a treatable trait in clinical practice. The circadian rhythm is controlled by the central clock located in the suprachiasmatic nucleus and clock genes (molecular clock) located in all cells. Dyslipidaemia and vascular inflammation are two hallmarks of atherosclerosis and numerous experimental studies conclude that they are under direct influence by both central and molecular clocks. This review will summarise the results of experimental studies on lipid metabolism, vascular inflammation and circadian rhythm, and translate them into the pathophysiology of atherosclerosis and cardiovascular disease. We discuss the effect of time-respected administration of medications in cardiovascular medicine. We review the evidence on the effect of bright light and melatonin on cardiovascular health, lipid metabolism and vascular inflammation. Finally, we suggest an agenda for future research and recommend on clinical practice. [ABSTRACT FROM AUTHOR]

A number of hereditary ataxias are caused by inborn errors of metabolism (IEM), most of which are highly heterogeneous in their clinical presentation. Prompt diagnosis is important because disease-specific therapies may be available. In this review, we offer a comprehensive overview of metabolic ataxias summarized by disease, highlighting novel clinical trials and emerging therapies with a particular emphasis on first-in-human gene therapies. We present disease-specific treatments if they exist and review the current evidence for symptomatic treatments of these highly heterogeneous diseases (where cerebellar ataxia is part of their phenotype) that aim to improve the disease burden and enhance quality of life. In general, a multimodal and holistic approach to the treatment of cerebellar ataxia, irrespective of etiology, is necessary to offer the best medical care. Physical therapy and speech and occupational therapy are obligatory. Genetic counseling is essential for making informed decisions about family planning. [ABSTRACT FROM AUTHOR]

Background: Intestinal barrier dysfunctions have been associated with liver steatosis and metabolic diseases. Besides nutritional factors, like a Western‐style diet (WSD), serotonin has been linked with leaky gut. Therefore, we aimed to evaluate the role of serotonin in the pathogenesis of intestinal barrier dysfunctions and liver steatosis in mice fed high‐fat and high‐sugar diets. Methods: 6–8 weeks old male serotonin reuptake transporter knockout mice (SERT−/−) and wild‐type controls (SERT+/+) were fed either a WSD or a control diet (CD) ad libitum with or without fructose 30% (F) added to the drinking water for 12 weeks. Markers of liver steatosis and intestinal barrier function were assessed. Key Results: SERT−/− mice showed increased weight gain compared with SERT+/+ mice when fed a WSD ± F for 12 weeks (p < 0.05), whereby SERT−/− mice exhibited reduced energy (−21%) intake. Furthermore, SERT knockout resulted in a more pronounced liver steatosis (p < 0.05), enhanced levels of endotoxin in portal vein plasma (p < 0.05), and increased liver expression of Tnf and Myd88 (p < 0.05), when mice were fed a WSD ± F. Finally, SERT−/− mice, when compared with SERT+/+ mice, had a decreased mRNA expression of Muc2 (p < 0.01), Ocln (p < 0.05), Cldn5 (p = 0.054) and 7 (p < 0.01), Defa5 (p < 0.05) and other antimicrobial peptides in the ileum. On the protein level, ZO‐1 (p < 0.01) and DEFA5 protein (p < 0.0001) were decreased. Conclusion and Inferences: Our data demonstrate that SERT knockout causes weight gain, liver steatosis, and leaky gut, especially in mice fed a WSD. Therefore, SERT induction could be a novel therapeutic approach to improve metabolic diseases associated with intestinal barrier dysfunction. [ABSTRACT FROM AUTHOR]

Although Maasai's traditional food system (TFS) is claimed to keep a low prevalence of metabolic diseases (MD), the link between its qualities and health benefits is not well established. An ethnobotanical survey was conducted to determine the link between health benefits and qualities of the Maasai TFS in Monduli, Arusha, Tanzania. The survey involved 21 Maasai TFS practitioners (MTPs) and revealed that the TFS has varieties of 19 dishes and a diversity of 78 flora species. The diversity of dishes and species had various potential health benefits: nutrition like Fe and vitamin A; therapeutic and protective effects against ailments including MD like gout, pressure, indigestion, and kidney disorders. Some food processing technologies (FPT) like nixtamalization, and meat roasting had potential protective effects against the MD. Cultural preferences and restrictions (CPR) for the food selection insured individual nutritional and health needs are met, and reinforcement of Maasai socio-structure and cohesion. Integrated protection and promotion measures are required to prevent unplanned nutritional transitions away from the TFS. Further research on the nutritional and medicinal roles of some FPT and the frequently used species could facilitate the protection and use of the TFS for the health benefits of especially marginalized people. Traditional food system (TFS) keeps a low prevalence of ailments including metabolic diseases (MD) in indigenous communities that uphold the cultural practices of their TFS. A variety of 19 Maasai foods (dishes) and a diversity of 78 flora species distributed in 63 genera and 39 families were parts of the Maasai TFS. Animal-based products, cereals, pulses, fruits, roots, and vegetables were the most frequently used food items in the Maasai TFS. Maasai food processing technologies FPT, a diversity of dishes and flora species, and cultural preferences and restrictions (CPR) developed for food selection constitute the qualities of the Maasai TFS. FPT, a diversity of dishes and flora species, and CPR are linked to health and cultural benefits. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) ions act as a second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. A lot of evidence demonstrates that the dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been shown. [ABSTRACT FROM AUTHOR]

Adiponectin, as an indispensable regulator of the immune system, is the most abundant adipokine and is mainly produced by white adipose tissue. Adiponectin mediates the positive effects on systemic metabolism by regulating associated downstream signalling pathways; however, accumulating evidence shows that adiponectin plays an important role in regulating the function of innate and adaptive immune cells in the development of obesity and its related diseases. In this review, we focus on the biological function of adiponectin in regulating innate and adaptive immunity and outline the key role of adiponectin in various metabolic diseases, which will highlight a potential direction for adiponectin‐based therapeutic interventions for metabolic diseases. [ABSTRACT FROM AUTHOR]

The circadian rhythm is a self-sustaining 24 h cycle that regulates physiological processes within the body, including cycles of alertness and sleepiness. Cells have their own intrinsic clock, which consists of several proteins that regulate the circadian rhythm of each individual cell. The core of the molecular clock in human cells consists of four main circadian proteins that work in pairs. The CLOCK-BMAL1 heterodimer and the PER-CRY heterodimer each regulate the other pair's expression, forming a negative feedback loop. Several other proteins are involved in regulating the expression of the main circadian genes, and can therefore also influence the circadian rhythm of cells. This review focuses on the existing knowledge regarding circadian gene variants in both the main and secondary circadian genes, and their association with various diseases, such as tumors, metabolic diseases, cardiovascular diseases, and sleep disorders. [ABSTRACT FROM AUTHOR]

Hydroxysafflor yellow A (HSYA) is a chalcone compound extracted from safflower. A growing number of discoveries suggest that HSYA has a better effect on metabolic diseases, including cancer, diabetes, and cardiovascular diseases, which has led to increasing attention on development and utilization in the pharmaceutical, food, and cosmetics industries. This review presents recent advances involved in the metabolic diseases and HSYA, and current evidence showing the importance of HSYA on metabolic signaling pathways, such as MAPK, PI3K/Akt et al. Although the research of HSYA metabolic regulation is only a beginning stage, it has already contributed to our current understanding of natural pigments. We also encourage further investigation to address the potential mechanism of HSYA under physiological and pathological conditions and further application in the pharmaceutical and food industries. [ABSTRACT FROM AUTHOR]

As a multi-potency cytokine, leptin not only plays a crucial role in controlling weight and energy homeostasis but also participates in the metabolic balance in the human body. Leptin is a small helical protein with a molecular weight of 16 kDa. It can interact with multiple subtypes of its receptors to initiate intracellular signal transduction and exerts physiological effects. Disturbances in leptin signaling may lead to obesity and a variety of metabolic diseases. Leptin was also found to be a critical factor in many diseases of the elderly. In this review, we focus on recent advances in the structural and molecular mechanisms of leptin signaling through its receptors with the aim of a deeper understanding of leptin-related diseases. • The structures of leptins are highly conserved across species. • LEPR-ECD forms a 2:2 quaternary complex with leptin to activate JAK/STAT, PI3K-AKT, MAPK, and other signaling pathways. • Leptin expression and secretion are influenced by a variety of physiological and pathological factors. • Leptin plays a critical role in many diseases of the elderly. [ABSTRACT FROM AUTHOR]

Metabolic disease is a complex disorder defined by a group with interrelated factors. There is growing evidence that obesity can lead to a variety of metabolic diseases, including diabetes and cardiovascular disease. Excessive adipose tissue (AT) deposition and ectopic accumulation can lead to increased peri-organ AT thickness. Dysregulation of peri-organ (perivascular, perirenal, and epicardial) AT is strongly associated with metabolic disease and its complications. The mechanisms include secretion of cytokines, activation of immunocytes, infiltration of inflammatory cells, involvement of stromal cells, and abnormal miRNA expression. This review discusses the associations and mechanisms by which various types of peri-organ AT affect metabolic diseases while addressing it as a potential future treatment strategy. • Obesity can cause various metabolic diseases. • Dysregulated peri-organ AT is linked to metabolic disease and complications. • Peri-organ AT is a valuable drug target for metabolic disease treatment. [ABSTRACT FROM AUTHOR]