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Genes Aug 2023Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet,... (Review)
Review
Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.
Topics: Humans; Oxalates; Diabetes Mellitus, Type 2; Hyperoxaluria, Primary; Kidney; Nephrolithiasis; Hypertension
PubMed: 37761859
DOI: 10.3390/genes14091719 -
Cell Reports. Medicine Aug 2023New approaches are needed to treat people whose obesity and type 2 diabetes (T2D) are driven by specific mechanisms. We investigate a deletion on chromosome 16p11.2...
New approaches are needed to treat people whose obesity and type 2 diabetes (T2D) are driven by specific mechanisms. We investigate a deletion on chromosome 16p11.2 (breakpoint 2-3 [BP2-3]) encompassing SH2B1, a mediator of leptin and insulin signaling. Phenome-wide association scans in the UK (N = 502,399) and Estonian (N = 208,360) biobanks show that deletion carriers have increased body mass index (BMI; p = 1.3 × 10) and increased rates of T2D. Compared with BMI-matched controls, deletion carriers have an earlier onset of T2D, with poorer glycemic control despite higher medication usage. Cystatin C, a biomarker of kidney function, is significantly elevated in deletion carriers, suggesting increased risk of renal impairment. In a Mendelian randomization study, decreased SH2B1 expression increases T2D risk (p = 8.1 × 10). We conclude that people with 16p11.2 BP2-3 deletions have early, complex obesity and T2D and may benefit from therapies that enhance leptin and insulin signaling.
Topics: Humans; Leptin; Diabetes Mellitus, Type 2; Obesity; Metabolic Diseases; Insulins; Adaptor Proteins, Signal Transducing
PubMed: 37586323
DOI: 10.1016/j.xcrm.2023.101155 -
Deutsche Medizinische Wochenschrift... Aug 2023Diabetes mellitus is the most common metabolic disease with >500 million people affected worldwide and currently 8,7 million in Germany. About 90% of diabetes cases are... (Review)
Review
Diabetes mellitus is the most common metabolic disease with >500 million people affected worldwide and currently 8,7 million in Germany. About 90% of diabetes cases are due to type 2 diabetes mellitus (T2D). This form of diabetes is characterized by an increased release of proinflammatory adipokines, endothelial dysfunction and hyperglycemia, among others. Hypertension and dyslipidemia are also very commonly present. The prevalence of cardiovascular disease is about 2-3 times higher in T2D than in age-matched individuals without a diagnosis of diabetes. Cardiovascular mortality is also about twice as high in people with diabetes compared to a non-diabetic population. People with diabetes are therefore generally considered a high-risk cardiovascular group and require special attention in the diagnosis and treatment of cardiovascular disease. Contributing factors to reduce high cardiovascular risk include a healthy lifestyle, normalization of blood pressure, optimization of blood lipid levels, and specific diabetes therapy tailored to cardiovascular risk. This review addresses the specific treatment options for reducing cardiovascular risk in patients with diabetes mellitus.
Topics: Humans; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Hypertension; Blood Pressure; Mediastinum; Risk Factors
PubMed: 37541293
DOI: 10.1055/a-1928-1360 -
International Journal of Molecular... Oct 2023Dysbiosis, generally defined as the disruption to gut microbiota composition or function, is observed in most diseases, including allergies, cancer, metabolic diseases,... (Review)
Review
Dysbiosis, generally defined as the disruption to gut microbiota composition or function, is observed in most diseases, including allergies, cancer, metabolic diseases, neurological disorders and diseases associated with autoimmunity. Dysbiosis is commonly associated with reduced levels of beneficial gut microbiota-derived metabolites such as short-chain fatty acids (SCFA) and indoles. Supplementation with these beneficial metabolites, or interventions to increase their microbial production, has been shown to ameliorate a variety of inflammatory diseases. Conversely, the production of gut 'dysbiotic' metabolites or by-products by the gut microbiota may contribute to disease development. This review summarizes the various 'dysbiotic' gut-derived products observed in cardiovascular diseases, cancer, inflammatory bowel disease, metabolic diseases including non-alcoholic steatohepatitis and autoimmune disorders such as multiple sclerosis. The increased production of dysbiotic gut microbial products, including trimethylamine, hydrogen sulphide, products of amino acid metabolism such as p-Cresyl sulphate and phenylacetic acid, and secondary bile acids such as deoxycholic acid, is commonly observed across multiple diseases. The simultaneous increased production of dysbiotic metabolites with the impaired production of beneficial metabolites, commonly associated with a modern lifestyle, may partially explain the high prevalence of inflammatory diseases in western countries.
Topics: Humans; Gastrointestinal Microbiome; Dysbiosis; Noncommunicable Diseases; Autoimmune Diseases; Neoplasms; Metabolic Diseases
PubMed: 37894934
DOI: 10.3390/ijms242015256 -
Nutrients Apr 2024As women age, their nutritional needs change, governed by changes in hormones, level of physical activity, and dietary intake [...].
As women age, their nutritional needs change, governed by changes in hormones, level of physical activity, and dietary intake [...].
Topics: Humans; Female; Postmenopause; Metabolic Diseases; Chronic Disease; Diet; Middle Aged; Exercise
PubMed: 38732576
DOI: 10.3390/nu16091329 -
Molecular Medicine (Cambridge, Mass.) Jul 2023The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in... (Review)
Review
The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer's disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.
Topics: Humans; Glucose; Lipid Metabolism; Diabetes Mellitus, Type 2; Protein Processing, Post-Translational; Phosphorylation; Proteins
PubMed: 37415097
DOI: 10.1186/s10020-023-00684-9 -
Orphanet Journal of Rare Diseases Aug 2023Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish... (Review)
Review
Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as "bone crises". Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as "enzymopathic gouts". Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson's disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.
Topics: Humans; Adult; Chondrocalcinosis; Gout; Joint Diseases; Metabolism, Inborn Errors; Hepatolenticular Degeneration
PubMed: 37563694
DOI: 10.1186/s13023-023-02810-6 -
Helicobacter Dec 2023The microbiota actively and extensively participates in the regulation of human metabolism, playing a crucial role in the development of metabolic diseases. Helicobacter... (Review)
Review
The microbiota actively and extensively participates in the regulation of human metabolism, playing a crucial role in the development of metabolic diseases. Helicobacter pylori (H. pylori), when colonizing gastric epithelial cells, not only induces local tissue inflammation or malignant transformation but also leads to systemic and partial changes in host metabolism. These shifts can be mediated through direct contact, toxic components, or indirect immune responses. Consequently, they influence various molecular metabolic events that impact nutritional status and iron absorption in the host. Unraveling the intricate and diverse molecular interaction links between H. pylori and human metabolism modulation is essential for understanding pathogenesis mechanisms and developing targeted treatments for related diseases. However, significant challenges persist in comprehensively understanding the complex association networks among H. pylori itself, the infected host's status, the host microbiome, and the immune response. Previous metabolomics research has indicated that H. pylori infection and eradication may selectively shape the metabolite and microbial profiles of gastric lesions. Yet, it remains largely unknown how these diverse metabolic pathways, including isovaleric acid, cholesterol, fatty acids, and phospholipids, specifically modulate gastric carcinogenesis or affect the host's serum metabolism, consequently leading to the development of metabolic-associated diseases. The direct contribution of H. pylori to metabolisms still lacks conclusive evidence. In this review, we summarize recent advances in clinical evidence highlighting associations between chronic H. pylori infection and metabolic diseases, as well as its potential molecular regulatory patterns.
Topics: Humans; Helicobacter pylori; Helicobacter Infections; Stomach; Homeostasis; Metabolic Diseases
PubMed: 37871913
DOI: 10.1111/hel.13030 -
The Journal of Biological Chemistry Oct 2023Following 3 decades of extensive research into PI3K signaling, it is now evidently clear that the underlying network does not equate to a simple ON/OFF switch. This is... (Review)
Review
Following 3 decades of extensive research into PI3K signaling, it is now evidently clear that the underlying network does not equate to a simple ON/OFF switch. This is best illustrated by the multifaceted nature of the many diseases associated with aberrant PI3K signaling, including common cancers, metabolic disease, and rare developmental disorders. However, we are still far from a complete understanding of the fundamental control principles that govern the numerous phenotypic outputs that are elicited by activation of this well-characterized biochemical signaling network, downstream of an equally diverse set of extrinsic inputs. At its core, this is a question on the role of PI3K signaling in cellular information processing and decision making. Here, we review the determinants of accurate encoding and decoding of growth factor signals and discuss outstanding questions in the PI3K signal relay network. We emphasize the importance of quantitative biochemistry, in close integration with advances in single-cell time-resolved signaling measurements and mathematical modeling.
Topics: Humans; Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Systems Biology; EGF Family of Proteins; Insulin-Like Growth Factor I; Nerve Growth Factor; Metabolic Diseases
PubMed: 37673340
DOI: 10.1016/j.jbc.2023.105224 -
Frontiers in Endocrinology 2023Apelin, a novel endogenous ligand of the G-protein-coupled receptor APJ, is encoded by the gene and can be hydrolyzed into multiple subtypes, with Apelin-13 being one... (Review)
Review
Apelin, a novel endogenous ligand of the G-protein-coupled receptor APJ, is encoded by the gene and can be hydrolyzed into multiple subtypes, with Apelin-13 being one of the most active subtypes of the Apelin family. Recent studies have revealed that Apelin-13 functions as an adipokine that participates in the regulation of different biological processes, such as oxidative stress, inflammation, apoptosis, and energy metabolism, thereby playing an important role in the prevention and treatment of various metabolic diseases. However, the results of recent studies on the association between Apelin-13 and various metabolic states remain controversial. Furthermore, Apelin-13 is regulated or influenced by various forms of exercise and could therefore be categorized as a new type of exercise-sensitive factor that attenuates metabolic diseases. Thus, in this review, our purpose was to focus on the relationship between Apelin-13 and related metabolic diseases and the regulation of response movements, with particular reference to the establishment of a theoretical basis for improving and treating metabolic diseases.
Topics: Humans; Apelin; Intercellular Signaling Peptides and Proteins; Apelin Receptors; Metabolic Diseases
PubMed: 38089606
DOI: 10.3389/fendo.2023.1285788