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Frontiers in Endocrinology 2024Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by... (Review)
Review
Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.
Topics: Humans; Diabetic Nephropathies; Lipid Metabolism; Animals; Lipid Metabolism Disorders; Gastrointestinal Microbiome
PubMed: 38742197
DOI: 10.3389/fendo.2024.1336402 -
International Journal of Molecular... Mar 2020Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2... (Review)
Review
Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1β (Interleukin-1β), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.
Topics: Animals; Atherosclerosis; Blood Pressure; Endothelium, Vascular; Humans; Inflammation; Lipid Metabolism Disorders; Vildagliptin
PubMed: 32218354
DOI: 10.3390/ijms21072275 -
Pharmaceutical Biology Dec 2023Gouty arthritis (GA) is a characteristically inflammatory disease often associated with lipid metabolism disorder. Huangqin Qingrechubi capsule (HQC) has been used for...
CONTEXT
Gouty arthritis (GA) is a characteristically inflammatory disease often associated with lipid metabolism disorder. Huangqin Qingrechubi capsule (HQC) has been used for the treatment of GA.
OBJECTIVE
To explore the mechanism of HQC in the treatment of GA.
MATERIALS AND METHODS
A total of 30 GA patients (GA group) and 30 healthy subjects [normal control (NC) group] were recruited. The GA group was treated with HQC (3.6 g/d) for 10 days. Lipid metabolism and inflammation indexes were detected. Five herbal names of HQC, or 'gouty arthritis', 'hyperlipidemia' and 'inflammation' were used as key words to search related databases for network pharmacological analysis. Subsequently, GA-fibroblast-like synoviocytes (FLSs) were stimulated with GA-peripheral blood mononuclear cells (PBMCs) (3:1) and treated with HQC drug-containing serum (20%). RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of HQC in improving GA.
RESULTS
In clinical observation, HQC decreased the expression of lncRNA H19 and IL-1β, and increased the expression of adiponectin (APN) and IL-4 in the GA group (about half). Through network pharmacology, the PI3K/AKT signaling pathway was identified. Cell experiments showed that HQC treatment reduced the viability of GA-FLSs (49.61%), up-regulated the expression of IL-4 (155.18%), IL-10 (165.13%), and APN (31.24%), and down-regulated the expression of lncRNA H19 (33.70%), IL-1β (64.70%), TNF-α (78.32%), p-PI3K (48.80%), and p-AKT (53.48%).
DISCUSSION AND CONCLUSIONS
HQC improved lipid metabolism disorder and inflammatory response of GA by regulating the lncRNA H19/APN/PI3K/AKT. Maintaining the stability of lipid metabolism may be an effective way to alleviate GA.
Topics: Humans; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Scutellaria baicalensis; RNA, Long Noncoding; Adiponectin; Lipid Metabolism; Leukocytes, Mononuclear; Interleukin-4; Signal Transduction; Inflammation; Arthritis, Gouty; Lipid Metabolism Disorders
PubMed: 36994890
DOI: 10.1080/13880209.2023.2191641 -
International Journal of Molecular... Nov 2020Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack... (Review)
Review
Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack of differentiation, loss of function or premature apoptosis. As a consequence, lipids can only be stored ectopically in non-adipocytes with the major health consequences as fatty liver and insulin resistance. This is a crucial difference to being slim where the fat cells are present and store lipids if needed. A simple clinical classification of lipodystrophies is based on congenital vs. acquired and generalized vs. partial disturbance of fat distribution. Complications in patients with lipodystrophy depend on the clinical manifestations. For example, in diabetes mellitus microangiopathic complications such as nephropathy, retinopathy and neuropathy may develop. In addition, due to ectopic lipid accumulation in the liver, fatty liver hepatitis may also develop, possibly with cirrhosis. The consequences of extreme hypertriglyceridemia are typically acute pancreatitis or eruptive xanthomas. The combination of severe hyperglycemia with dyslipidemia and signs of insulin resistance can lead to premature atherosclerosis with its associated complications of coronary heart disease, peripheral vascular disease and cerebrovascular changes. Overall, lipodystrophy is rare with an estimated incidence for congenital (<1/1.000.000) and acquired (1-9/100.000) forms. Due to the rarity of the syndrome and the phenotypic range of metabolic complications, only studies with limited patient numbers can be considered. Experimental animal models are therefore useful to understand the molecular mechanisms in lipodystrophy and to identify possible therapeutic approaches.
Topics: Acyltransferases; Adipose Tissue; Animals; Atherosclerosis; Body Fat Distribution; Coronary Disease; Diabetes Mellitus; Disease Models, Animal; Fatty Liver; Humans; Hypertriglyceridemia; Insulin Resistance; Lamin Type A; Lipid Metabolism; Lipodystrophy; Pancreatitis; Xanthomatosis
PubMed: 33233602
DOI: 10.3390/ijms21228778 -
Current Diabetes Reports Oct 2018Insulin resistance (IR) is recognized to play an important role in the pathogenesis of dyslipidemia. This review summarizes the complex interplay between IR and... (Review)
Review
PURPOSE OF REVIEW
Insulin resistance (IR) is recognized to play an important role in the pathogenesis of dyslipidemia. This review summarizes the complex interplay between IR and dyslipidemia in people with and without diabetes.
RECENT FINDINGS
IR impacts the metabolism of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) by several mechanisms. Trials with insulin sensitizing therapies, including biguanides and thiazolidinediones, have provided inconsistent results on lipid lowering in people with and without diabetes. In this review, we focus on the pathophysiological interplay between IR and dyslipidemia and recapitulate lipid and lipoprotein data from insulin-sensitizing trials. Further research elucidating the reciprocal relationship between IR and dyslipidemia is needed to better target these important risk factors for cardiovascular disease.
Topics: Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Insulin; Insulin Resistance; Lipid Metabolism Disorders; Metabolic Syndrome
PubMed: 30328521
DOI: 10.1007/s11892-018-1101-6 -
Biomolecules Nov 2023Many vascular diseases are linked to lipid metabolism disorders, which cause lipid accumulation and peroxidation in the vascular wall. These processes lead to... (Review)
Review
Many vascular diseases are linked to lipid metabolism disorders, which cause lipid accumulation and peroxidation in the vascular wall. These processes lead to degenerative changes in the vessel, such as phenotypic transformation of smooth muscle cells and dysfunction and apoptosis of endothelial cells. In intracranial aneurysms, the coexistence of lipid plaques is often observed, indicating localized lipid metabolism disorders. These disorders may impair the function of the vascular wall or result from it. We summarize the literature on the relationship between lipid metabolism disorders and intracranial aneurysms below.
Topics: Humans; Intracranial Aneurysm; Endothelial Cells; Lipid Metabolism; Lipid Metabolism Disorders; Lipids
PubMed: 38002334
DOI: 10.3390/biom13111652 -
Environment International Dec 2023Deoxynivalenol (DON) is a trichothecene toxin that mainly produced by strains of Fusarium spp. DON contamination is widely distributed and is a global food safety...
Deoxynivalenol (DON) is a trichothecene toxin that mainly produced by strains of Fusarium spp. DON contamination is widely distributed and is a global food safety threat. Existing studies have expounded its harmful effects on growth inhibition, endocrine disruption, immune function impairment, and reproductive toxicity. In energy metabolism, DON suppresses appetite, reduces body weight, triggers lipid oxidation, and negatively affects cholesterol and fatty acid homeostasis. In this study, high-fat diet (HFD) induced obese C57BL/6J mice were orally treated with 0.1 mg/kg bw/d and 1.0 mg/kg bw/d DON for 4 weeks. The lipid metabolism of mice and the molecular mechanisms were explored. The data showed that although DON reduced body weight and fat mass in HFD mice, it significantly increased their serum triglyceride concentrations, disturbance of serum lipid metabolites, impaired glucose, and resulted in insulin intolerance in mice. In addition, the transcriptional and expression changes of lipid metabolism genes in the liver and epididymis (EP) adipose indicate that the DON-mediated increase in serum triglycerides is caused by lipoprotein lipase (LPL) inhibition in EP adipose. Furthermore, DON down-regulates the expression of LPL through the PPARγ signaling pathway in EP adipose. These results are further confirmed by the serum lipidomics analysis. In conclusion, DON acts on the PPARγ pathway of white adipose to inhibit the expression of LPL, mediate the increase of serum triglyceride in obese mice, disturb the homeostasis of lipid metabolism, and increase the risk of cardiovascular disease. This study reveals the interference mechanism of DON on lipid metabolism in obese mice and provides a theoretical basis for its toxic effect in obese individuals.
Topics: Humans; Male; Animals; Mice; Diet, High-Fat; Lipid Metabolism; Mice, Obese; PPAR gamma; Mice, Inbred C57BL; Obesity; Body Weight; Lipid Metabolism Disorders; Cholesterol; Triglycerides; Liver
PubMed: 38008010
DOI: 10.1016/j.envint.2023.108345 -
Scientific Reports Sep 2023Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques followed by intracellular neurofibrillary tangles...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques followed by intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. An unrestrained immune response by microglia, the resident cells of the central nervous system (CNS), leads to neuroinflammation which can amplify AD pathology. AD pathology is also driven by metabolic dysfunction with strong correlations between dementia and metabolic disorders such as diabetes, hypercholesterolemia, and hypertriglyceridemia. Since elevated cholesterol and triglyceride levels appear to be a major risk factor for developing AD, we investigated the lipid metabolism transcriptome in an AD versus non-AD state using RNA-sequencing (RNA-seq) and microarray datasets from N9 cells and murine microglia. We identified 52 differentially expressed genes (DEG) linked to lipid metabolism in LPS-stimulated N9 microglia versus unstimulated control cells using RNA-seq, 86 lipid metabolism DEG in 5XFAD versus wild-type mice by microarray, with 16 DEG common between both datasets. Functional enrichment and network analyses identified several biological processes and molecular functions, such as cholesterol homeostasis, insulin signaling, and triglyceride metabolism. Furthermore, therapeutic drugs targeting lipid metabolism DEG found in our study were identified. Focusing on drugs that target genes associated with lipid metabolism and neuroinflammation could provide new targets for AD drug development.
Topics: Animals; Mice; Alzheimer Disease; Lipid Metabolism; Microglia; Transcriptome; Neuroinflammatory Diseases; Hypercholesterolemia; Triglycerides
PubMed: 37684405
DOI: 10.1038/s41598-023-41897-6 -
Acta Neuropathologica Communications Feb 2014Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by the accumulation of α-synuclein protein in the cytoplasm of oligodendrocytes,... (Review)
Review
Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by the accumulation of α-synuclein protein in the cytoplasm of oligodendrocytes, the myelin-producing support cells of the central nervous system (CNS). The brain is the most lipid-rich organ in the body and disordered metabolism of various lipid constituents is increasingly recognized as an important factor in the pathogenesis of several neurodegenerative diseases. α-Synuclein is a 17 kDa protein with a close association to lipid membranes and biosynthetic processes in the CNS, yet its precise function is a matter of speculation, particularly in oligodendrocytes. α-Synuclein aggregation in neurons is a well-characterized feature of Parkinson's disease and dementia with Lewy bodies. Epidemiological evidence and in vitro studies of α-synuclein molecular dynamics suggest that disordered lipid homeostasis may play a role in the pathogenesis of α-synuclein aggregation. However, MSA is distinct from other α-synucleinopathies in a number of respects, not least the disparate cellular focus of α-synuclein pathology. The recent identification of causal mutations and polymorphisms in COQ2, a gene encoding a biosynthetic enzyme for the production of the lipid-soluble electron carrier coenzyme Q10 (ubiquinone), puts membrane transporters as central to MSA pathogenesis, although how such transporters are involved in the early myelin degeneration observed in MSA remains unclear. The purpose of this review is to bring together available evidence to explore the potential role of membrane transporters and lipid dyshomeostasis in the pathogenesis of α-synuclein aggregation in MSA. We hypothesize that dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes underlies the unique neuropathology of MSA.
Topics: Alkyl and Aryl Transferases; Brain; Humans; Lipid Metabolism Disorders; Multiple System Atrophy; Mutation
PubMed: 24502382
DOI: 10.1186/2051-5960-2-15 -
International Journal of Environmental... Dec 2021The aim of this study was to assess lipid disorders in children from five ethnic groups, both urban and indigenous, from northern and central Mexico. We measured the...
The aim of this study was to assess lipid disorders in children from five ethnic groups, both urban and indigenous, from northern and central Mexico. We measured the lipid profile to determine the ability of the body mass index (BMI) to discriminate an abnormally high lipid level using receiving operating characteristics (ROC). We analyzed the association and interaction of obesity and ethnicity with lipid disorders using generalized linear models in 977 children. The highest prevalence of lipid disorders (high TG, high TC, high LDL, high APOB, and dyslipidemia) was found in central Mexico-Mexico City and urban northern Mexico. The BMI performed better at predicting low HDL in Seris, a northern indigenous group (0.95, CI: 0.69-0.85), and Mexico City (0.75, CI: 0.69-0.82), and high LDL in Puebla (central Mexico, 0.80, CI: 0.69-0.85). Obesity significantly ( < 0.05) increases lipid disorders by around two times (OR~2) for almost all lipid markers. Obesity and ethnic interaction increase the lipid disorders by more than five times for different lipid markers and ethnic groups (high total cholesterol OR = 5.31; low HDL OR = 5.11, and dyslipidemia OR = 5.68). Lipid disorders are not restricted to children with high BMIs, but obesity exacerbates these. The emerging lipid disorder risk depends on the ethnic group.
Topics: Body Mass Index; Cholesterol, HDL; Dyslipidemias; Ethnicity; Humans; Mexico; Obesity; Risk Factors; Triglycerides
PubMed: 34886385
DOI: 10.3390/ijerph182312659