High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

Metabolites, Год журнала: 2023, Номер 13(2), С. 253 - 253

Опубликована: Фев. 9, 2023

Alterations affecting high-density lipoproteins (HDLs) are one of the various abnormalities observed in dyslipidemia type 2 diabetes mellitus (T2DM) and obesity. Kinetic studies have demonstrated that catabolism HDL particles is accelerated. Both size lipidome proteome significantly modified, which likely contributes to some functional defects HDLs. Studies on cholesterol efflux capacity yielded heterogeneous results, ranging from a defect an improvement. Several indicate HDLs less able inhibit nuclear factor kappa-B (NF-κB) proinflammatory pathway, subsequently, adhesion monocytes endothelium their recruitment into subendothelial space. In addition, antioxidative function diminished, thus facilitating deleterious effects oxidized low-density vasculature. Lastly, HDL-induced activation endothelial nitric oxide synthase effective T2DM metabolic syndrome, contributing several defects, such as impaired promote vasodilatation repair, difficulty counteracting production reactive oxygen species inflammation.

Язык: Английский

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The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 9, 2024

Abstract Atherosclerosis is one of the leading causes death worldwide. miR-26 a potential biomarker atherosclerosis. Standardized diagnostic tests for (MIR26-DX) have been developed, but fastest progress has in predicting efficacy IFN-α therapy hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as ACC1/2 inhibitors GS-0976, PF-05221304, MK-4074; DGAT2 IONIS-DGAT2Rx, PF-06427878, PF-0685571, PF-07202954; COL1A1 inhibitor HT-100; stimulants 68 Ga-CBP8 RCT-01; CPT1A etomoxir, perhexiline, teglicar; FBP1 CS-917 MB07803; SMAD7 mongersen, investigated clinical trials. Interestingly, better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, LIB003, Recombinant was also Therefore, promising target agent development. promotes foam cell formation reducing ABCA1 ARL4C Multiple materials can be used to deliver miR-26, it unclear which material most suitable mass production applications. This review focuses on use treating support it.

Язык: Английский

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Unravelling cysteine-deficiency-associated rapid weight loss

Nature, Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

Around 40% of the US population and 1 in 6 individuals worldwide have obesity, with incidence surging globally1,2. Various dietary interventions, including carbohydrate, fat and, more recently, amino acid restriction, been explored to combat this epidemic3-6. Here we investigated impact removing individual acids on weight profiles mice. We show that conditional cysteine restriction resulted most substantial loss when compared essential amounting 30% within week, which was readily reversed. found deficiency activated integrated stress response oxidative response, amplify each other, leading induction GDF15 FGF21, partly explaining phenotype7-9. Notably, observed lower levels tissue coenzyme A (CoA), has considered be extremely stable10, resulting reduced mitochondrial functionality metabolic rewiring. This results energetically inefficient anaerobic glycolysis defective tricarboxylic cycle, sustained urinary excretion pyruvate, orotate, citrate, α-ketoglutarate, nitrogen-rich compounds acids. In summary, our investigation reveals by depleting GSH CoA, exerts a maximal loss, metabolism signalling other restrictions. These findings suggest strategies for addressing range diseases growing obesity crisis.

Язык: Английский

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Quartet of APOCs and the Different Roles They Play in Diabetes

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2023, Номер 43(7), С. 1124 - 1133

Опубликована: Май 25, 2023

APOA1 and APOB are the structural proteins of high-density lipoprotein APOB-containing lipoproteins, such as low-density very lipoprotein, respectively. The 4 smaller APOCs (APOC1, APOC2, APOC3, APOC4) exchangeable apolipoproteins; they readily transferred among lipoproteins lipoproteins. regulate plasma triglyceride cholesterol levels by modulating substrate availability activities enzymes interacting with interfering uptake through hepatic receptors. Of APOCs, APOC3 has been best studied in relation to diabetes. Elevated serum predict incident cardiovascular disease progression kidney people type 1 Insulin suppresses levels, accordingly, elevated associate insulin deficiency resistance. Mechanistic studies a mouse model diabetes have demonstrated that acts causal pathway diabetes-accelerated atherosclerosis. mechanism is likely due ability slow clearance triglyceride-rich their remnants, thereby causing an increased accumulation atherogenic remnants lesions Less known about roles APOC1, APOC4

Язык: Английский

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APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Март 21, 2024

Abstract Background Recent studies have demonstrated that APOC1 is associated with cancer progression, exerting cancer-promoting and immune infiltration-promoting effects. Nevertheless, there currently no report on the presence of in ovarian (OV). Method In this study, we conducted data analysis using GEO TCGA databases. We a thorough bioinformatics to investigate function OV, utilizing various platforms including cBioPortal, STRING, GeneMANIA, LinkedOmics, GSCALite, TIMER, CellMarker. Additionally, performed immunohistochemical staining tissue microarrays vitro cellular assays validate our findings. Result Our findings reveal expression significantly upregulated OV compared normal tissues. Importantly, patients high levels show poorer prognosis. Furthermore, study exerted crucial promoting capacity cells proliferate, migrate, invade. identified genes co-expressed are primarily adaptive responses. Notably, exhibit correlation M2 Tumor-associated Macrophages (TAMs). Conclusion emerges as promising prognostic biomarker for exhibits significant association TAMs OV.

Язык: Английский

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A Novel Macrophage Subpopulation Conveys Increased Genetic Risk of Coronary Artery Disease

Circulation Research, Год журнала: 2024, Номер 135(1), С. 6 - 25

Опубликована: Май 15, 2024

Coronary artery disease (CAD), the leading cause of death worldwide, is influenced by both environmental and genetic factors. Although over 250 risk loci have been identified through genome-wide association studies, specific causal variants their regulatory mechanisms are still largely unknown, particularly in disease-relevant cell types such as macrophages.

Язык: Английский

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Stereo-seq of the prefrontal cortex in aging and Alzheimer’s disease

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 8, 2025

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in prefrontal cortex (PFC). We present first subcellular-resolution spatial transcriptome atlas of human (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages age-matched controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions laminar structure, exposed AD-related shifts layer-to-layer cell-cell interactions. Notably, we identified genes highly upregulated stressed neurons nearby glial cells, where diminished stress-response interactions that promote Aβ clearance. Further, cell-type-specific co-expression analysis three neuronal modules linked to neuroprotection, protein dephosphorylation, regulation, all downregulated as progresses. ZNF460 a transcription factor regulating these modules, offering potential therapeutic target. In summary, this provides valuable insight into AD's molecular mechanisms. (AD). Here, authors AD, revealing alterations.

Язык: Английский

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Effects of a dietary intervention with lacto-ovo-vegetarian and Mediterranean diets on apolipoproteins and inflammatory cytokines: results from the CARDIVEG study

Nutrition & Metabolism, Год журнала: 2024, Номер 21(1)

Опубликована: Фев. 1, 2024

Abstract Background Apolipoproteins have been recently proposed as novel markers of cardiovascular disease (CVD) risk. However, evidence regarding effects diet on apolipoproteins is limited. Aim To compare the Mediterranean (MD) and lacto-ovo vegetarian (VD) traditional CVD risk factors in participants with low-to-moderate Methods Fifty-two (39 women; 49.1 ± 12.4 years), followed MD VD for 3 months each. Medical dietary information was collected at baseline. Anthropometric parameters blood samples were obtained beginning end interventions. Results resulted significant improvement anthropometric lipid profiles. Both diets led to a reduction most inflammatory parameters. As apolipoproteins, change observed ApoC-I after (+ 24.4%; p = 0.020). negative correlation between ApoC-III carbohydrates (R − 0.29; 0.039) whereas ApoD saturated fats 0.38; 0.006). A positive emerged HDL 0.33; 0.017) plasma triglycerides 0.32; 0.020) 0.30; 0.031). IL-17 be positively correlated ApoB 0.31; 0.028) 0.019). Subgroup analysis revealed from both diets, especially women, individuals older than 50 years-old or < factors. Conclusions seem improve risk, however, showed greater effect some subgroups, thus suggesting how may influence new potential Trial registration : registered clinicaltrials.gov (identifier: NCT02641834) December 2015.

Язык: Английский

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Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

BioFactors, Год журнала: 2024, Номер 50(5), С. 922 - 956

Опубликована: Апрель 25, 2024

Abstract High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved cholesterol transport inflammation modulation. The proteome of HDL particles is indeed complex distinct from other components the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on 15 or so traditionally named “apo” lipoproteins. Important metabolizing enzymes closely working apolipoproteins also discussed. Apolipoproteins stand out for their integral stability, structure, function, metabolism. unique structure functions each apolipoprotein influence important processes such regulation These interactions shape stability performance particles. HDLs multifaceted roles beyond diseases (CVDs) various physiological disease states. Therefore, detailed exploration these can offer valuable insights into potential diagnostic markers therapeutic targets. This comprehensive article aims to provide an in‐depth understanding apolipoproteins, highlighting structures, functions, contributions processes. Exploiting knowledge holds great improving enhancing efflux, modulating inflammatory processes, ultimately benefiting individuals by limiting risks CVDs inflammation‐based pathologies. Understanding nature all expands our metabolism, sheds light pathological implications, paves way advancements diagnosis, prevention, treatment inflammatory‐related disorders.

Язык: Английский

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Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling

Clinical Proteomics, Год журнала: 2024, Номер 21(1)

Опубликована: Март 1, 2024

In persons with dyslipidemia, a high residual risk of cardiovascular disease remains despite lipid lowering therapy. Current prediction mainly focuses on low-density lipoprotein cholesterol (LDL-c) levels, neglecting other contributing factors. Moreover, the efficacy LDL-c by statins resulting in reduced is only partially effective. Secondly, from metrological viewpoint falls short as reliable measurand. Both direct and calculated tests produce inaccurate test results at low end under aggressive As underperform both clinically metrologically, there an urging need for molecularly defined biomarkers. Over years, apolipoproteins have emerged promising biomarkers context they are functional workhorses metabolism. Among these, apolipoprotein B (ApoB), present all atherogenic particles, has demonstrated to outperform LDL-c. Other apolipoproteins, such Apo(a) - characteristic emerging factor lipoprotein(a) -, ApoC-III inhibitor triglyceride-rich clearance attracted attention well. To support personalized medicine, we move markers, like apolipoproteins. Molecularly diagnosis targeted therapy require measured This review provides summary scientific validity (patho)physiological role nine serum Apo(a), ApoB, ApoC-I, ApoC-II, ApoC-III, ApoE its phenotypes, ApoA-I, ApoA-II, ApoA-IV, metabolism, their association disease, potential markers when multiplex panel.

Язык: Английский

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