ABSTRACT
Bietti crystalline dystrophy (BCD) is a rare heritable retinal disease characterized by crystal deposition primarily in the retina. It is associated with atrophy of the retinal pigment epithelium (RPE) and is caused by variants in CYP4V2 , which encodes a cytochrome P450 hemethiolate protein superfamily member. CYP4V2 is involved in the selective hydrolysis of saturated medium chain fatty acids, and patients with BCD demonstrate abnormalities in fatty acid metabolism, including abnormal lipid profiles and the accumulation of the pathogenic crystals within the RPE, which leads to the visual pathologies characteristic of BCD. However, the precise identity of the crystals is currently unknown, and BCD has no established extraocular manifestations. Here, we report granulomatous hepatitis associated with abundant diffuse crystalline clefts in the hepatic parenchyma in 3 patients with retinal dystrophy and dyslipidemia: 2 with pathogenic CYP4V2 variants and 1 patient with clinical ophthalmologic findings suggestive of BCD but without available genetic testing. The unique and striking histologic features unifying the liver biopsies in all 3 patients strongly support a process related to abnormal fatty acid metabolism underlying the genetic disease of BCD, expanding the spectrum of BCD and shedding light on the importance of CYP4V2 in systemic fatty acid metabolism.
Subject(s)
Corneal Dystrophies, Hereditary , Cytochrome P450 Family 4 , Fatty Acids , Humans , Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/pathology , Corneal Dystrophies, Hereditary/metabolism , Cytochrome P450 Family 4/genetics , Cytochrome P450 Family 4/metabolism , Female , Male , Fatty Acids/metabolism , Middle Aged , Retinal Diseases/genetics , Retinal Diseases/pathology , Adult , Liver/pathology , Liver Diseases/pathology , Liver Diseases/genetics , Liver Diseases/metabolism , Biopsy , Dyslipidemias/genetics , Dyslipidemias/pathologyABSTRACT
BACKGROUND/AIM: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis. PATIENTS AND METHODS: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles. RESULTS: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa. CONCLUSION: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication.
Subject(s)
Gastric Mucosa , Gastritis , Helicobacter Infections , Helicobacter pylori , Tertiary Care Centers , Humans , Helicobacter Infections/pathology , Helicobacter Infections/complications , Helicobacter Infections/microbiology , Male , Female , Romania/epidemiology , Helicobacter pylori/isolation & purification , Middle Aged , Gastritis/pathology , Gastritis/microbiology , Gastric Mucosa/pathology , Gastric Mucosa/microbiology , Adult , Lipids/blood , Lipids/analysis , Retrospective Studies , Aged , Metaplasia/pathology , Biopsy , Dyslipidemias/pathology , Dyslipidemias/bloodABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is associated with atherogenic dyslipidemia and an increased risk of cardiovascular events. Previous studies have suggested an inverse relationship between NAFLD severity and lipoprotein(a) [Lp(a)] level, but contemporary data from the U.S. are lacking. Lp(a), lipid profile, apolipoproteins, and nuclear magnetic resonance-based lipoprotein particle concentrations were measured in 151 patients with biopsy-proven NAFLD. Levels were compared between those with nonalcoholic fatty liver (NAFL) on histology and non-alcoholic steatohepatitis (NASH). Median age was 55 [48, 62] years, 67% of patients were women, 83% were White, 43% had NAFL, and 57% had NASH. Triglyceride level was higher and high-density lipoprotein-cholesterol (HDL-C) was lower among those with NASH as compared with NAFL. Circulating apolipoprotein-B (ApoB) and low-density lipoprotein particle concentration (LDL-P) were 9% and 17% higher in the NASH group as compared with NAFL, respectively. Contrastingly, Lp(a) concentration was 50% lower in NASH relative to NAFL group. Hepatocyte ballooning, lobular inflammation, and fibrosis on histology were inversely associated with Lp(a) concentration. NAFLD severity has a discordant association with Lp(a) and other markers of atherogenic dyslipidemia. This relationship may have implications for prognosticating cardiovascular disease risk in patients with NAFLD.
Subject(s)
Dyslipidemias , Non-alcoholic Fatty Liver Disease , Humans , Female , Middle Aged , Male , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/pathology , Lipoprotein(a) , Inflammation/complications , Cholesterol, HDL , Dyslipidemias/complications , Dyslipidemias/pathology , Liver/pathologyABSTRACT
BACKGROUND: The global burden of cardiovascular diseases continues to rise, and it is increasingly acknowledged that guidelines based on traditional risk factors fail to identify a substantial fraction of people who develop cardiovascular diseases. Fat in the pancreas could be one of the unappreciated risk factors. This study aimed to investigate the associations of dyslipidemia states with fat in the pancreas. METHODS: All participants underwent magnetic resonance imaging on the same 3.0 T scanner for quantification of fat in the pancreas, analyzed as both binary (i.e., fatty change of the pancreas) and continuous (i.e., intra-pancreatic fat deposition) variables. Statistical analyses were adjusted for body mass index, glycated hemoglobin, fasting insulin, ethnicity, age, and sex. RESULTS: There were 346 participants studied. On most adjusted analyses, high-density lipoprotein cholesterol dyslipidemia was significantly associated with both fatty change of the pancreas (p = 0.010) and intra-pancreatic fat deposition (p = 0.008). Neither low-density lipoprotein cholesterol dyslipidemia nor triglyceride dyslipidemia were significantly associated with fatty change of the pancreas and intra-pancreatic fat deposition. The absence of any dyslipidemia was inversely associated with both fatty change of the pancreas (p = 0.016) and intra-pancreatic fat deposition (p < 0.001). CONCLUSIONS: Dyslipidemias are uncoupled when it comes to the relationship with fat in the pancreas, with only high-density lipoprotein cholesterol dyslipidemia having a consistent and strong link with it. The residual cardiovascular diseases risk may be attributed to fatty change of the pancreas.
Subject(s)
Cardiovascular Diseases , Dyslipidemias , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/pathology , Pancreas/diagnostic imaging , Pancreas/pathology , Risk Factors , Cholesterol, HDL , Dyslipidemias/complications , Dyslipidemias/pathologyABSTRACT
Obesity and overweight result in metabolic changes that build up as risk factors for the development of the main non-communicable diseases. Among these alterations, dyslipidemia is an important risk factor for cardiovascular diseases (CDV) and is expressed in elevated plasma levels of triacylglycerols, cholesterol, and low-density-lipoprotein (LDL, VLDL) and decreased plasma levels of high-density lipoprotein (HDL). Passiflora tenuifila Killip is a native passion fruit species of the Brazilian Midwest region and is a good source of proanthocyanidins and dietary fibers. Proanthocyanidins are a class of phenolic compounds that are attributed with improving lipoprotein profile properties, translated as improved LDL/HDL ratio. Fibers are fermented by the gut microbiota and produce short-chain fatty acids (SCFA), also involved in the regulation of energetic metabolism.. A 30-consecutive-day-long intervention with lyophilized P. tenuifila flour was performed in eutrophic and obese subjects. Passion fruit ingestion increased fecal production of acetate, key SCFA in the modulation of lipid metabolism; reduced body fat percentage in all subjects; and reduced total cholesterol (TC) of subjects who presented basal CT > 130 mg/dL. After the intervention, plasma lipidomic analysis detected 44 statistically significant lipids, regardless of BMI. Considering the study population with altered TC, reduced levels of glycerophospholipids were observed, a lipid class studied for their involvement in CVD. The intake of P. tenuifila contributed to the improvement in cardiovascular risk markers and acts on lipid metabolism. These effects may be due to synergic action between the bioactive compounds in the fruit. Still, other studies are necessary to identify mechanisms related to the action of bioactives of P. tenuifila, which can be better directed by this lipidomic approach
A obesidade e o sobrepeso são preocupações resultam em alterações metabólicas que se acumulam como fatores de risco para o desenvolvimento a longo prazo das principais doenças crônicas não transmissíveis. Dentre essas alterações, a dislipidemia um importante fator de risco para doenças cardiovasculares (DCV), expressa em níveis plasmáticos elevados de triacilgliceróis, colesterol e das lipoproteínas de baixa densidade (VLDL, LDL), e níveis diminuídos da lipoproteína de alta densidade (HDL). Passiflora tenuifila Killip é uma espécie de maracujá nativa da região Centro-Oeste brasileira, e é uma boa fonte de proantocianidinas e fibras alimentares. As proantocianidinas são compostos fenólicos com reportados efeitos na melhora do perfil de lipoproteínas, traduzida como a relação LDL/HDL. As fibras são fermentadas pela microbiota intestinal e produzem ácidos graxos de cadeia curta (AGCC), metabólitos também envolvidos na regulação do metabolismo energético.. Assim, a lipidômica não-target é aplicada como ferramenta exploratória neste estudo: uma intervenção de 30 dias consecutivos de ingestão de P. tenuifila na forma de farinha liofilizada em indivíduos eutróficos e obesos. O consumo do maracujá promoveu aumento da produção fecal de acetato, AGCC importante na modulação do metabolismo lipídico; a redução do percentual de gordura corporal em todos os indivíduos; e redução do colesterol total (CT) para os indivíduos com CT > 130 mg/dL. A análise lipidômica do plasma detectou 44 lipídios estatisticamente relevantes, independentemente do IMC, após a intervenção. Considerando a população do estudo com CT alterado, foi observada uma redução de glicerofosfolipídios, classe de lipídios estudada pelo seu envolvimento em DCV. Assim, a ingestão de P. tenuifila contribui para a melhora nos marcadores de risco cardiovascular e atua no metabolismo lipídico. Estes efeitos podem ser decorrentes de sinergia entre os diversos compostos bioativos do fruto. Ainda, outros estudos são necessários para identificar mecanismos relacionados a ação dos bioativos da P. tenuifila e estes podem ser mais bem direcionados pela lipidômica
Subject(s)
Passiflora/adverse effects , Lipidomics/instrumentation , Heart Disease Risk Factors , Obesity/complications , Dyslipidemias/pathologyABSTRACT
This study aimed to investigate the effect of cerium oxide nanoparticles (CeO2-NPs) on non-alcoholic fatty liver disease in postmenopausal obesity and the underlying mechanisms.64 adult female rats were allocated into Sham, ovariectomized (OVX), high-fat high-fructose dietfed- OVX (HFHF-OVX), and HFHF-OVX-CeO2-NPs-treated (CeO2-HFHF-OVX) groups. OVX and HFHF-OVX rats presented a significant increase in overall and visceral obesity, dyslipidemia, liver enzymes, serum malondialdehyde, liver TNF-α, TGF-ß1 and free fatty acids, liver X receptor (LXR) expression associated with decreased serum total antioxidant capacity and liver short heterodimer partner (SHP) expression vs. Sham group. Also, histomorphometric studies displayed a significant higher scores of liver steatosis, inflammation and fibrosis. All these parameters were significantly improved by CeO2-NPs treatment in CeO2-HFHF-OVX vs. HFHF-OVX rats. Thus, CeO2-NPs treatment ameliorates liver steatosis, steatohepatitis, and fibrosis in postmenopausal obese rats via alleviation of obesity, dyslipidemia, modulating liver genes involved in lipid metabolism (LXR and SHP), decreasing liver lipogenesis besides its antioxidant and anti-inflammatory effects.
Subject(s)
Dyslipidemias , Nanoparticles , Non-alcoholic Fatty Liver Disease , Animals , Female , Humans , Rats , Anti-Inflammatory Agents , Antioxidants/metabolism , Cerium , Dyslipidemias/complications , Dyslipidemias/metabolism , Dyslipidemias/pathology , Fatty Acids, Nonesterified/metabolism , Fibrosis , Fructose/metabolism , Liver/metabolism , Liver X Receptors/metabolism , Malondialdehyde/metabolism , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/complications , Obesity/drug therapy , Obesity/metabolism , Ovariectomy , Postmenopause , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1ß-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer.
Subject(s)
Dyslipidemias , Monocytes , Animals , Carcinogenesis/pathology , Cell Transformation, Neoplastic/pathology , Dyslipidemias/pathology , Inflammation/pathology , Mice , Mice, Inbred C57BL , Monocytes/pathology , Myeloid Cells/pathology , Tumor MicroenvironmentABSTRACT
Elevated liver de novo lipogenesis contributes to non-alcoholic steatohepatitis (NASH) and can be inhibited by targeting acetyl-CoA carboxylase (ACC). However, hypertriglyceridemia limits the use of pharmacological ACC inhibitors as a monotherapy. ATP-citrate lyase (ACLY) generates acetyl-CoA and oxaloacetate from citrate, but whether inhibition is effective for treating NASH is unknown. Here, we characterize a new mouse model that replicates many of the pathological and molecular drivers of NASH and find that genetically inhibiting ACLY in hepatocytes reduces liver malonyl-CoA, oxaloacetate, steatosis, and ballooning as well as blood glucose, triglycerides, and cholesterol. Pharmacological inhibition of ACLY mirrors genetic inhibition but has additional positive effects on hepatic stellate cells, liver inflammation, and fibrosis. Mendelian randomization of human variants that mimic reductions in ACLY also associate with lower circulating triglycerides and biomarkers of NASH. These data indicate that inhibiting liver ACLY may be an effective approach for treatment of NASH and dyslipidemia.
Subject(s)
ATP Citrate (pro-S)-Lyase , Dyslipidemias , Non-alcoholic Fatty Liver Disease , ATP Citrate (pro-S)-Lyase/antagonists & inhibitors , Acetyl-CoA Carboxylase , Animals , Dyslipidemias/drug therapy , Dyslipidemias/pathology , Liver , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Oxaloacetates/metabolism , TriglyceridesABSTRACT
Obesity is a multi-systemic disorder of energy balance. Despite intense investigation, the determinants of energy homeostasis remain incompletely understood, and efficacious treatments against obesity and its complications are lacking. Here, we demonstrate that conferred arginine iminohydrolysis by the bacterial virulence factor and arginine deiminase, arcA, promotes mammalian energy expenditure and insulin sensitivity and reverses dyslipidemia, hepatic steatosis, and inflammation in obese mice. Extending this, pharmacological arginine catabolism via pegylated arginine deiminase (ADI-PEG 20) recapitulates these metabolic effects in dietary and genetically obese models. These effects require hepatic and whole-body expression of the autophagy complex protein BECN1 and hepatocyte-specific FGF21 secretion. Single-cell ATAC sequencing further reveals BECN1-dependent hepatocyte chromatin accessibility changes in response to ADI-PEG 20. The data thus reveal an unexpected therapeutic utility for arginine catabolism in modulating energy metabolism by activating systemic autophagy, which is now exploitable through readily available pharmacotherapy.
Subject(s)
Arginine/metabolism , Autophagy , Energy Metabolism , Hydrolases/chemistry , Hydrolases/metabolism , Polyethylene Glycols/chemistry , Animals , Beclin-1/metabolism , Dependovirus/metabolism , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diet, Western , Dyslipidemias/pathology , Fatty Liver/pathology , Fibroblast Growth Factors/metabolism , Glucose/metabolism , Hepatocytes/metabolism , Homeostasis , Insulin Resistance , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , ThermogenesisABSTRACT
Abstract Resistant starch is particularly concerned with beneficial effects in regulating blood glucose concentration and lipid metabolism, reducing the risk of diabetes and cardiovascular diseases. This study aimed to validate the effects of wheat starch acetate containing 32.1% resistant starch on postprandial blood glucose response and lipid profile on obesity, dyslipidemia Swiss mice induced by a high-fat diet. The result showed that there was a restriction on postprandial hyperglycemia and remained stable for 2 hours after meal efficiently comparing with the control group fed natural wheat starch. Simultaneously, when maintaining the dose of 5g/kg once or twice a day for 8 weeks, wheat starch acetate to be able to reduce body weight and blood glucose, triglyceride, cholesterol levels compared to the control group (p<0.05)
Subject(s)
Animals , Male , Mice , Dyslipidemias/pathology , Resistant Starch/analysis , Acetates , Obesity/pathology , Starch/agonists , Cholesterol/adverse effects , Glucose/adverse effectsABSTRACT
Thyroid hormones control lipid metabolism by exhibiting specific effects on the liver and adipose tissue in a coordinated manner. Different diseases of the thyroid gland can result in hypothyroidism. Hypothyroidism is frequently associated with dyslipidemia. Hypothyroidism-associated dyslipidemia subsequently results in intrahepatic accumulation of fat, leading to nonalcoholic fatty liver disease (NAFLD), which leads to the development of hepatic insulin resistance. The prevalence of NAFLD in the western world is increasing, and evidence of its association with hypothyroidism is accumulating. Since hypothyroidism has been identified as a modifiable risk factor of NAFLD and recent data provides evidence that selective thyroid hormone receptor ß (THR-ß) agonists are effective in the treatment of dyslipidemia and NAFLD, interest in potential therapeutic options for NAFLD targeting these receptors is growing. In this review, we summarize current knowledge regarding clinical and molecular data exploring the association of hypothyroidism, dyslipidemia and NAFLD.
Subject(s)
Dyslipidemias/pathology , Hypothyroidism/complications , Insulin Resistance , Lipid Metabolism , Non-alcoholic Fatty Liver Disease/pathology , Animals , Dyslipidemias/etiology , Humans , Non-alcoholic Fatty Liver Disease/etiology , Risk FactorsABSTRACT
Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/- physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (-13.1% and -5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (-5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (ß = 0.10; p = 0.05), HbA1c (ß = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (ß = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (ß = 0.16; p = 0.02) and leptin (ß = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724).
Subject(s)
Chin/pathology , Neck/pathology , Obesity/therapy , Subcutaneous Fat/pathology , Weight Reduction Programs/methods , Adiposity , Adult , Body Composition , Body Mass Index , Chin/diagnostic imaging , Cholesterol, HDL/blood , Dyslipidemias/blood , Dyslipidemias/pathology , Dyslipidemias/therapy , Female , Humans , Insulin Resistance , Magnetic Resonance Imaging , Male , Middle Aged , Neck/diagnostic imaging , Obesity/blood , Obesity/pathology , Subcutaneous Fat/diagnostic imaging , Treatment Outcome , Triglycerides/blood , Weight Loss , Whole Body ImagingABSTRACT
Impaired hepatic glucose and lipid metabolism are hallmarks of type 2 diabetes. Increased sulfide production or sulfide donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver- enriched mitochondrial SOP enzyme thiosulfate sulfurtransferase (Tst-/- mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia, and fatty liver. Unexpectedly, hepatic sulfide levels are normal in Tst-/- mice because of exaggerated induction of sulfide disposal, with associated suppression of global protein persulfidation and nuclear respiratory factor 2 target protein levels. Hepatic proteomic and persulfidomic profiles converge on gluconeogenesis and lipid metabolism, revealing a selective deficit in medium-chain fatty acid oxidation in Tst-/- mice. We reveal a critical role of TST in hepatic metabolism that has implications for sulfide donor strategies in the context of metabolic disease.
Subject(s)
Diabetes Mellitus/pathology , Dyslipidemias/pathology , Gluconeogenesis , Liver/pathology , Sulfides/metabolism , Thiosulfate Sulfurtransferase/physiology , Animals , Diabetes Mellitus/etiology , Diabetes Mellitus/metabolism , Dyslipidemias/etiology , Dyslipidemias/metabolism , Glucose/metabolism , Lipid Metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-E2-Related Factor 2/metabolism , Proteome/metabolismABSTRACT
Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profiles; the girls were on the whole more impacted.
Subject(s)
Atherosclerosis/complications , Coronary Artery Disease/complications , Diabetes Mellitus, Type 1/etiology , Heart Disease Risk Factors , Hypertension/complications , Adolescent , Blood Pressure/physiology , Child , Dyslipidemias/pathology , Female , Humans , Hyperglycemia/pathology , Male , Obesity/pathology , Sedentary Behavior , Sex FactorsABSTRACT
CD36 (cluster of differentiation 36) is a membrane protein involved in lipid metabolism and has been linked to pathological conditions associated with metabolic disorders, such as diabetes and dyslipidemia. A case-control study was conducted and included 177 patients with type-2 diabetes mellitus (T2DM) and 173 control subjects to study the involvement of CD36 gene rs1761667 (G>A) and rs1527483 (C>T) polymorphisms in the pathogenesis of T2DM and dyslipidemia among Jordanian population. Lipid profile, blood sugar, gender and age were measured and recorded. Also, genotyping analysis for both polymorphisms was performed. Following statistical analysis, 10 different neural networks and machine learning (ML) tools were used to predict subjects with diabetes or dyslipidemia. Towards further understanding of the role of CD36 protein and gene in T2DM and dyslipidemia, a protein-protein interaction network and meta-analysis were carried out. For both polymorphisms, the genotypic frequencies were not significantly different between the two groups (p > 0.05). On the other hand, some ML tools like multilayer perceptron gave high prediction accuracy (≥ 0.75) and Cohen's kappa (κ) (≥ 0.5). Interestingly, in K-star tool, the accuracy and Cohen's κ values were enhanced by including the genotyping results as inputs (0.73 and 0.46, respectively, compared to 0.67 and 0.34 without including them). This study confirmed, for the first time, that there is no association between CD36 polymorphisms and T2DM or dyslipidemia among Jordanian population. Prediction of T2DM and dyslipidemia, using these extensive ML tools and based on such input data, is a promising approach for developing diagnostic and prognostic prediction models for a wide spectrum of diseases, especially based on large medical databases.
Subject(s)
CD36 Antigens/genetics , Diabetes Mellitus, Type 2/genetics , Dyslipidemias/genetics , Genetic Predisposition to Disease , Diabetes Mellitus, Type 2/pathology , Dyslipidemias/pathology , Female , Genetic Association Studies , Humans , Machine Learning , Male , Middle Aged , Polymorphism, Single Nucleotide/geneticsABSTRACT
This study aimed to investigate the prevalence of dyslipidemia and its related factors among urban adults aged 35 to 79 years in Southwestern China. From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,221 people aged 35-79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. The prevalence of high triglycerides (≥ 2.3 mmol/L), high total cholesterol (≥ 6.2 mmol/L), high low-density lipoprotein cholesterol (≥ 4.1 mmol/L), low high-density lipoprotein cholesterol (< 1.0 mmol/L), and dyslipidemia were 15.7% (95% confidence interval, 15.0-16.4%), 5.4% (4.9-5.8%), 2.5% (2.2-2.8%), 5.7% (5.3-6.2%), and 27.4% (26.5-28.2%), respectively. The prevalence of dyslipidemia was positively correlated with higher education level, monthly income over 2000 CNY, smoking, hypertension, diabetes, overweight and obesity, and central obesity, and negatively correlated with daily physical exercise. The prevalence of dyslipidemia in Southwestern China is lower than the national average level, with high triglycerides being the most common form of dyslipidemia.
Subject(s)
Dyslipidemias/epidemiology , Adult , Aged , Biomarkers/blood , China/epidemiology , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Dyslipidemias/blood , Dyslipidemias/pathology , Female , Humans , Hypertension/blood , Hypertension/epidemiology , Male , Middle Aged , Obesity/blood , Obesity/epidemiology , Prevalence , Prognosis , Risk FactorsABSTRACT
Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 µM; 2793 ng/mL), rosuvastatin (10 µM; 4815 ng/mL), ezetimibe (1.22 µM; 500 ng/mL), atorvastatin plus ezetimibe (5 µM + 1.22 µM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 µM + 1.22 µM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 µM; 10 µg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone.
Subject(s)
Atherosclerosis/prevention & control , Atorvastatin/pharmacology , Dyslipidemias/prevention & control , Ezetimibe/pharmacology , Rosuvastatin Calcium/administration & dosage , Atherosclerosis/drug therapy , Atherosclerosis/genetics , Atherosclerosis/pathology , Cholesterol/blood , Cholesterol, LDL/blood , Drug Therapy, Combination , Dyslipidemias/drug therapy , Dyslipidemias/genetics , Dyslipidemias/pathology , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Intercellular Adhesion Molecule-1/genetics , Occludin/genetics , Risk Factors , Zonula Occludens-1 Protein/geneticsABSTRACT
BACKGROUND: Obesity is a metabolic chronic disease with important associated morbidities and mortality. Bariatric surgery is the most effective treatment for maintaining long-term weight loss in severe obesity and, consequently, for decreasing obesity-related complications, including chronic inflammation. AIM: To explore changes in components of the inflammasome machinery after bariatric surgery and their relation with clinical/biochemical parameters at baseline and 6 months after bariatric surgery. PATIENTS AND METHODS: Twenty-two patients with morbid-obesity that underwent bariatric surgery (sleeve gastrectomy and Roux-en-Y gastric bypass) were included. Epidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and 6 months after bariatric surgery. Inflammasome components and inflammatory-associated factors [nucleotide-binding oligomerization domain-like receptors (NLRs), inflammasome activation components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators) were evaluated in peripheral blood mononuclear cells (PBMCs) at baseline and 6 months after bariatric surgery. Clinical molecular correlations/associations were analyzed. Functional parameters (lipid accumulation/viability/apoptosis) were analyzed in response to specific inflammasome components silencing in liver HepG2 cells). RESULTS: A profound dysregulation of inflammasome components after bariatric surgery was found, especially in NLRs and cell-cycle and DNA damage regulators. Several components were associated with baseline metabolic comorbidities including type 2 diabetes (C-C motif chemokine ligand 2/C-X-C motif chemokine receptor 1/sirtuin 1), hypertension (absent in melanoma 2/ASC/purinergic receptor P2X 7), and dyslipidemia [C-X-C motif chemokine ligand 3 (CXCL3)/NLR family pyrin domain containing (NLRP) 7) and displayed changes in their molecular profile 6 months after bariatric surgery. The gene expression fingerprint of certain factors NLR family CARD domain containing 4 (NLRC4)/NLRP12/CXCL3)/C-C motif chemokine ligand 8/toll-like receptor 4) accurately differentiated pre- and postoperative PBMCs. Most changes were independent of the performed surgical technique. Silencing of NLRC4/NLRP12 resulted in altered lipid accumulation, apoptosis rate, and cell viability in HepG2 cells. CONCLUSION: Bariatric surgery induces a profound alteration in the gene expression pattern of components of the inflammasome machinery in PBMCs. Expression and changes of certain inflammasome components are associated to baseline metabolic comorbidities, including type 2 diabetes, and may be related to the improvement and reversion of some obesity-related comorbidities after bariatric surgery.
Subject(s)
Bariatric Surgery/adverse effects , Diabetes Mellitus, Type 2/pathology , Dyslipidemias/pathology , Inflammation Mediators/metabolism , Inflammation/pathology , Leukocytes, Mononuclear/pathology , Obesity, Morbid/surgery , Adult , Biomarkers/metabolism , Chronic Disease , Cohort Studies , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/metabolism , Dyslipidemias/etiology , Dyslipidemias/metabolism , Female , Follow-Up Studies , Gastrectomy/adverse effects , Humans , Inflammasomes/metabolism , Inflammation/etiology , Inflammation/metabolism , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Obesity, Morbid/pathology , PrognosisABSTRACT
BACKGROUND: The numbers of confirmed cases of coronavirus disease 2019 (COVID-19) and COVID-19 related deaths are still increasing, so it is very important to determine the risk factors of COVID-19. Dyslipidemia is a common complication in patients with COVID-19, but the association of dyslipidemia with the severity and mortality of COVID-19 is still unclear. The aim of this study is to analyze the potential association of dyslipidemia with the severity and mortality of COVID-19. METHODS: We searched the PubMed, Embase, MEDLINE, and Cochrane Library databases for all relevant studies up to August 24, 2020. All the articles published were retrieved without language restriction. All analysis was performed using Stata 13.1 software and Mantel-Haenszel formula with fixed effects models was used to compare the differences between studies. The Newcastle Ottawa scale was used to assess the quality of the included studies. RESULTS: Twenty-eight studies involving 12,995 COVID-19 patients were included in the meta-analysis, which was consisted of 26 cohort studies and 2 case-control studies. Dyslipidemia was associated with the severity of COVID-19 (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.11-1.44, P = 0.038, I2 = 39.8%). Further, patients with dyslipidemia had a 2.13-fold increased risk of death compared to patients without dyslipidemia (95% CI 1.84-2.47, P = 0.001, I2 = 66.4%). CONCLUSIONS: The results proved that dyslipidemia is associated with increased severity and mortality of COVID-19. Therefore, we should monitor blood lipids and administer active treatments in COVID-19 patients with dyslipidemia to reduce the severity and mortality.
Subject(s)
COVID-19/pathology , Dyslipidemias/pathology , Lipids/blood , Severity of Illness Index , COVID-19/mortality , Dyslipidemias/mortality , Humans , Risk Factors , SARS-CoV-2ABSTRACT
The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.