-
Obesity (Silver Spring, Md.) Feb 2024Obesity is a chronic metabolic disease that is closely related to type 2 diabetes mellitus, cardiovascular diseases, nonalcoholic fatty liver disease, obstructive sleep... (Review)
Review
Obesity is a chronic metabolic disease that is closely related to type 2 diabetes mellitus, cardiovascular diseases, nonalcoholic fatty liver disease, obstructive sleep apnea, and osteoarthritis. The prevalence of obesity is increasing rapidly every year and is recognized as a global public health problem. In recent years, the role of epigenetics in the development of obesity and related diseases has been recognized and is currently a research hotspot. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification in the eukaryotic RNA, including mRNA and noncoding RNA. Several studies have shown that the m6A modifications in the target mRNA and the corresponding m6A regulators play a significant role in lipid metabolism and are strongly associated with the pathogenesis of obesity-related diseases. In this review, the latest research findings regarding the role of m6A methylation in obesity and related metabolic diseases are summarized. The authors' aim is to highlight evidence that suggests the clinical utility of m6A modifications and the m6A regulators as novel early prediction biomarkers and precision therapeutics for obesity and obesity-related diseases.
Topics: Humans; Diabetes Mellitus, Type 2; Obesity; RNA, Messenger; Methylation
PubMed: 37989724
DOI: 10.1002/oby.23932 -
Reproductive Sciences (Thousand Oaks,... Nov 2023Hyperandrogenism is an endocrine disorder affecting a large population of reproductive-aged women, thus proportionally high number of fetuses are subjected to prenatal... (Review)
Review
Hyperandrogenism is an endocrine disorder affecting a large population of reproductive-aged women, thus proportionally high number of fetuses are subjected to prenatal androgenic exposure (PNA). The short-term stimulations at critical ontogenetic stages can wield lasting influences on the health. The most commonly diagnosed conditions in reproductive age women is polycystic ovary syndrome (PCOS). PNA may affect the growth and development of many systems in the whole body and disrupts the normal metabolic trajectory in the offspring of PCOS, contributing to the prevalence of cardiovascular and metabolic diseases (CVMD), including myocardial hypertrophy, hypertension, hyperinsulinemia, insulin resistance, hyperglycemia, obesity, and dyslipidemia, which are the leading causes of hospitalizations in young PCOS offspring. In this review, we focus on the effects of prenatal androgenic exposure on the cardiovascular and metabolic diseases in offspring, discuss the possible pathogenesis respectively, and summarize potential management strategies to improve metabolic health of PCOS offspring. It is expected that the incidence of CVMD and the medical burden will be reduced in the future.
Topics: Pregnancy; Female; Humans; Adult; Polycystic Ovary Syndrome; Androgens; Hyperandrogenism; Metabolic Diseases; Obesity; Insulin Resistance; Cardiovascular Diseases
PubMed: 37380913
DOI: 10.1007/s43032-023-01286-w -
Frontiers in Endocrinology 2023Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate... (Review)
Review
Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate various important physiological processes such as cell growth, apoptosis, senescence, and differentiation. Numerous studies have demonstrated that sphingolipids are strongly associated with glucose metabolism and insulin resistance. Insulin resistance, including peripheral insulin resistance and brain insulin resistance, is closely related to the occurrence and development of many metabolic diseases. In addition to metabolic diseases, like type 2 diabetes, brain insulin resistance is also involved in the progression of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the specific mechanism of sphingolipids in brain insulin resistance has not been systematically summarized. This article reviews the involvement of sphingolipids in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain.
Topics: Humans; Insulin Resistance; Diabetes Mellitus, Type 2; Sphingolipids; Neurodegenerative Diseases; Brain
PubMed: 37867511
DOI: 10.3389/fendo.2023.1243132 -
Biomedicine & Pharmacotherapy =... Sep 2023With the continuous improvement of people's living standard, the incidence of metabolic diseases is gradually increasing in recent years. There is growing interest in... (Review)
Review
With the continuous improvement of people's living standard, the incidence of metabolic diseases is gradually increasing in recent years. There is growing interest in finding drugs to treat metabolic diseases from natural compounds due to their good efficacy and limited side effects. Over the past few decades, many phytochemicals derived from natural plants, such as berberine, curcumin, quercetin, resveratrol, rutin, and hesperidin, have been shown to have good pharmacological activity against metabolic diseases in preclinical studies. More importantly, clinical trials using these phytochemicals to treat metabolic diseases have been increasing. This review comprehensively summarizes the clinical progress of phytochemicals derived from natural plants in the treatment of several metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). Accumulating clinical evidence shows that a total of 18 phytochemicals have good therapeutic effects on the three metabolic diseases by lowering blood glucose and lipid levels, reducing insulin resistance, enhancing insulin sensitivity, increasing energy expenditure, improving liver function, and relieving inflammation and oxidative stress. The information will help us better understand the medicinal value of these phytochemicals and promote their clinical application in the treatment of metabolic diseases.
Topics: Humans; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Insulin Resistance; Obesity; Phytochemicals
PubMed: 37542856
DOI: 10.1016/j.biopha.2023.115274 -
The Lancet. Diabetes & Endocrinology Sep 2023Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of... (Review)
Review
Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades. In this Review, we revisit the scientific evidence supporting the presence of a strong bidirectional feedback loop between several viral infections and metabolic diseases. We discuss how viruses might lead to the development or progression of metabolic diseases and conversely, how metabolic diseases might increase the severity of a viral infection. Furthermore, we discuss the clinical relevance of the current evidence on the relationship between viral infections and metabolic disease and the present and future challenges that should be addressed by the scientific community and health authorities.
Topics: Humans; Clinical Relevance; Virus Diseases; Metabolic Diseases; Public Health
PubMed: 37524103
DOI: 10.1016/S2213-8587(23)00154-7 -
Life Sciences Oct 2023Bile acids (BAs) function as detergents promoting nutrient absorption and as hormones regulating nutrient metabolism. Most BAs are key regulatory factors of... (Review)
Review
Bile acids (BAs) function as detergents promoting nutrient absorption and as hormones regulating nutrient metabolism. Most BAs are key regulatory factors of physiological activities, which are involved in the regulation of glucose, lipid, and drug metabolisms. Hepatic and intestinal diseases have close connections with the systemic cycling disorders of BAs. The abnormal in BA absorption came up with overmuch BAs could be involved in the pathophysiology of liver and bowel and metabolic disorders such as fatty liver diseases and inflammatory bowel diseases. The primary BAs (PBAs), which are synthesized in the liver, can be transformed into the secondary BAs (SBAs) by gut microbiota. The transformation processes are tightly associated with the gut microbiome and the host endogenous metabolism. The BA biosynthesis gene cluster bile-acid-inducible operon is essential for modulating BA pool, gut microbiome composition, and the onset of intestinal inflammation. This forms a bidirectional interaction between the host and its gut symbiotic ecosystem. The subtle changes in the composition and abundance of BAs perturb the host physiological and metabolic activity. Therefore, maintaining the homeostasis of BAs pool contributes to the balance of the body's physiological and metabolic system. Our review aims to dissect the molecular mechanisms underlying the BAs homeostasis, assess the key factors sustaining the homeostasis and the role of BA acting on host diseases. By linking the BAs metabolic disorders and their associated diseases, we illustrate the effects of BAs homeostasis on health and potential clinical interventions can be taken under the latest research findings.
Topics: Humans; Bile Acids and Salts; Ecosystem; Liver; Homeostasis; Metabolic Diseases
PubMed: 37422071
DOI: 10.1016/j.lfs.2023.121919 -
Acta Pharmacologica Sinica Jul 2024G protein-coupled receptors (GPCRs) are expressed in a variety of cell types and tissues, and activation of GPCRs is involved in enormous metabolic pathways, including... (Review)
Review
G protein-coupled receptors (GPCRs) are expressed in a variety of cell types and tissues, and activation of GPCRs is involved in enormous metabolic pathways, including nutrient synthesis, transportation, storage or insulin sensitivity, etc. This review intends to summarize the regulation of metabolic homeostasis and mechanisms by a series of GPCRs, such as GPR91, GPR55, GPR119, GPR109a, GPR142, GPR40, GPR41, GPR43 and GPR120. With deep understanding of GPCR's structure and signaling pathways, it is attempting to uncover the role of GPCRs in major metabolic diseases, including metabolic syndrome, diabetes, dyslipidemia and nonalcoholic steatohepatitis, for which the global prevalence has risen during last two decades. An extensive list of agonists and antagonists with their chemical structures in a nature of small molecular compounds for above-mentioned GPCRs is provided as pharmacologic candidates, and their preliminary data of preclinical studies are discussed. Moreover, their beneficial effects in correcting abnormalities of metabolic syndrome, diabetes and dyslipidemia are summarized when clinical trials have been undertaken. Thus, accumulating data suggest that these agonists or antagonists might become as new pharmacotherapeutic candidates for the treatment of metabolic diseases.
Topics: Humans; Receptors, G-Protein-Coupled; Animals; Metabolic Diseases; Drug Development; Signal Transduction
PubMed: 38326623
DOI: 10.1038/s41401-023-01215-2 -
Medicine Oct 2023Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological... (Review)
Review
Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such as the eyes, kidneys, heart, and brain, and lead to increased patient mortality. Diabetes mellitus is a major global health issue, and its incidence and prevalence have increased significantly in recent years. Moreover, the incidence is expected to continue to rise as more people adopt a Western lifestyle and diet. Thus, it is essential to understand the epidemiology, pathogenesis, risk factors, and treatment of vascular complications to aid patients in managing the disease effectively. This paper provides a comprehensive review of the literature to clarify the above content. Furthermore, this paper also delves into the correlation between novel risk factors, such as long noncoding RNAs, gut microbiota, and nonalcoholic fatty liver disease, with diabetic vascular complications.
Topics: Humans; Diabetes Mellitus; Diabetic Angiopathies; Risk Factors; Hyperglycemia; Cardiovascular Diseases
PubMed: 37800828
DOI: 10.1097/MD.0000000000035285 -
Neuroscience Oct 2023Diabetes Mellitus (DM) and Alzheimer's disease (AD) have been two of the most common chronic diseases affecting people worldwide. Type 2 DM (T2DM) is a metabolic disease... (Review)
Review
Diabetes Mellitus (DM) and Alzheimer's disease (AD) have been two of the most common chronic diseases affecting people worldwide. Type 2 DM (T2DM) is a metabolic disease depicted by insulin resistance, dyslipidemia, and chronic hyperglycemia while AD is a neurodegenerative disease marked by Amyloid β (Aβ) accumulation, neurofibrillary tangles aggregation, and tau phosphorylation. Various clinical, epidemiological, and lipidomics studies have linked those diseases claiming shared pathological pathways raising the assumption that diabetic patients are at an increased risk of developing AD later in their lives. Insulin resistance is the tipping point beyond where advanced glycation end (AGE) products and free radicals are produced leading to oxidative stress and lipid peroxidation. Additionally, different types of lipids are playing a crucial role in the development and the relationship between those diseases. Lipidomics, an analysis of lipid structure, formation, and interactions, evidently exhibits these lipid changes and their direct and indirect effect on Aβ synthesis, insulin resistance, oxidative stress, and neuroinflammation. In this review, we have discussed the pathophysiology of T2DM and AD, the interconnecting pathological pathways they share, and the lipidomics where different lipids such as cholesterol, phospholipids, sphingolipids, and sulfolipids contribute to the underlying features of both diseases. Understanding their role can be beneficial for diagnostic purposes or introducing new drugs to counter AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Insulin Resistance; Neurodegenerative Diseases; Lipidomics; Diabetes Mellitus, Type 2; Lipids
PubMed: 37652288
DOI: 10.1016/j.neuroscience.2023.08.033 -
Journal of Inherited Metabolic Disease Jan 2024Gene therapy clinical trials are rapidly expanding for inherited metabolic liver diseases whilst two gene therapy products have now been approved for liver based... (Review)
Review
Gene therapy clinical trials are rapidly expanding for inherited metabolic liver diseases whilst two gene therapy products have now been approved for liver based monogenic disorders. Liver-directed gene therapy has recently become an option for treatment of haemophilias and is likely to become one of the favoured therapeutic strategies for inherited metabolic liver diseases in the near future. In this review, we present the different gene therapy vectors and strategies for liver-targeting, including gene editing. We highlight the current development of viral and nonviral gene therapy for a number of inherited metabolic liver diseases including urea cycle defects, organic acidaemias, Crigler-Najjar disease, Wilson disease, glycogen storage disease Type Ia, phenylketonuria and maple syrup urine disease. We describe the main limitations and open questions for further gene therapy development: immunogenicity, inflammatory response, genotoxicity, gene therapy administration in a fibrotic liver. The follow-up of a constantly growing number of gene therapy treated patients allows better understanding of its benefits and limitations and provides strategies to design safer and more efficacious treatments. Undoubtedly, liver-targeting gene therapy offers a promising avenue for innovative therapies with an unprecedented potential to address the unmet needs of patients suffering from inherited metabolic diseases.
Topics: Humans; Liver Diseases; Genetic Therapy; Metabolic Diseases; Hemophilia A
PubMed: 38171926
DOI: 10.1002/jimd.12709