Lipids in Health and Disease最新文献

{"title":"Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation.","authors":"Haoran Jiang, Yuan Zeng, Xiaoye Yuan, Liwen Chen, Xuni Xu, Xue Jiang, Quan Li, Gang Li, Han Yang","doi":"10.1186/s12944-024-02364-x","DOIUrl":"10.1186/s12944-024-02364-x","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) continues to pose a significant obstacle in the field of oncology. Dysregulation of lipid metabolism, notably upregulated ketogenesis, has emerged as a hallmark of TNBC, yet its role in metastasis has been elusive. Here, by utilizing clinical specimens and experimental models, the study demonstrates that increased ketogenesis fosters TNBC metastasis by promoting the up-regulation of β-hydroxybutyrate (β-OHB), a key ketone body. Mechanistically, β-OHB facilitates β-hydroxybutyrylation (Kbhb) of Calpastatin (CAST), an endogenous calpain (CAPN) inhibitor, at K43, blocking the interaction with CAPN and subsequently promoting FAK phosphorylation and epithelial‒mesenchymal transition (EMT). In conclusion, the study reveals a novel regulatory axis linking ketogenesis to TNBC metastasis, shedding light on the intricate interplay between metabolic reprogramming and tumor progression.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"371"},"PeriodicalIF":3.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAT10 promotes liver lipogenesis in mouse through N4-acetylcytidine modification of Srebf1 and Scap mRNA.","authors":"Zhouqi Wang, Xinxing Wan, Md Asaduzzaman Khan, Lin Peng, Xiaoying Sun, Xuan Yi, Ke Chen","doi":"10.1186/s12944-024-02360-1","DOIUrl":"10.1186/s12944-024-02360-1","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction associated steatotic liver disease (MASLD), closely linked to excessive lipogenesis, induces chronic liver disease. MASLD often cause other metabolic diseases, such as cardiovascular disease, diabetes and obesity. However, the mechanism of N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) mRNA modification in lipogenesis of MASLD has not been fully elucidated. This study investigated the role of NAT10 in lipogenesis targeting mRNA ac4C modification.</p><p><strong>Methods: </strong>The expression of NAT10 in mouse liver was assessed after a 12-week high-fat diet. In addition, the expression of NAT10 also was detected after AML12 hepatocytes cells were treated with 150 µmol/L palmitic acid (PA). The ac4C mRNA modification was performed by dot blotting. Oil red O staining and the mRNA expression of Srebf1, Acaca and Fasn were used to assess lipogenesis in AML12 cells with NAT10 overexpression or knockdown. acRIP-PCR and NAT10 RIP-PCR were used to verify the Srebf1 and Scap mRNA ac4C modification by NAT10. Furthermore, the liver lipogenesis was evaluated by AAV-mediated target knockdown of NAT10 in mouse liver and treating a specific inhibitor, Remodelin.</p><p><strong>Results: </strong>This study revealed that NAT10 is significantly upregulated in liver lipogenesis after a 12-week high-fat diet. NAT10 and ac4C mRNA modification were also drastically increased in AML12 cells after treated with 150 µmol/L PA. Silencing of NAT10 notably inhibited the lipogenesis in AML12 cells and AAV-mediated target knockdown of NAT10 in mouse liver. The acRIP-PCR and NAT10-RIP-PCR revealed that NAT10 ac4C modified Srebf1 and Scap mRNA, the critical modulator of liver lipogenesis, to regulate liver lipogenesis. Besides, Remodelin strongly inhibited liver lipogenesis, including liver TG, serum ALT, AST, TG and TC level and glucose metabolism.</p><p><strong>Conclusions: </strong>NAT10 mediates ac4C modification of Srebf1 and Scap mRNA, thereby affecting lipogenesis in the liver. This study provided a new target for the treatment of MASLD.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"368"},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From gene to therapy: a review of deciphering the role of ABCD1 in combating X-Linked adrenoleukodystrophy.","authors":"Xinxin Zuo, Zeyu Chen","doi":"10.1186/s12944-024-02361-0","DOIUrl":"10.1186/s12944-024-02361-0","url":null,"abstract":"<p><p>X-linked adrenoleukodystrophy (X-ALD) is a severe genetic disorder caused by ABCD1 mutations, resulting in the buildup of very-long-chain fatty acids, leading to significant neurological decline and adrenal insufficiency. Despite advancements in understanding the mechanisms of X-ALD, its pathophysiology remains incompletely understood, complicating the development of effective treatments. This review provides a comprehensive overview of X-ALD, with a focus on the genetic and biochemical roles of ABCD1 and the impacts of its mutations. Current therapeutic approaches are evaluated, discussing their limitations, and emphasizing the need to fully elucidate the pathogenesis of X-ALD. Additionally, this review highlights the importance of international collaboration to enhance systematic data collection and advance biomarker discovery, ultimately improving patient outcomes with X-ALD.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"369"},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An equation for calculating small dense low-density lipoprotein cholesterol.","authors":"Tianjiao Han, Zhe Piao, Zhiguo Yu, Wanqi Xu, Xiaofeng Cui","doi":"10.1186/s12944-024-02345-0","DOIUrl":"10.1186/s12944-024-02345-0","url":null,"abstract":"<p><strong>Objective: </strong>Small dense low-density lipoprotein cholesterol (sdLDL-C), as an emerging atherogenic factor of cardiovascular diseases, requires additional tests. We aimed to establish a sdLDL-C equation using standard lipid profile and evaluate its capacity of identifying the residual cardiovascular risk beyond LDL-C and apolipoprotein B (ApoB).</p><p><strong>Methods: </strong>This cross-sectional study included 25 435 participants from Health Management Cohort and 11 628 participants from China Health and Retirement Longitudinal Study (CHARLS) to construct and evaluate the sdLDL-C equation by least-squares regression model. The equation for sdLDL-C depended on low-density lipoprotein cholesterol (LDL-C) and an interaction term between LDL-C and the natural log of triglycerides (TG).</p><p><strong>Results: </strong>The modified equation (sdLDL-C = 0.14*ln(TG)*LDL-C - 0.45*LDL-C + 10.88) was more accurate than the original equation in validation set (slope = 0.783 vs. 0.776, MAD = 5.228 vs. 5.396). Using the 80th percentile (50 mg/dL) as a risk-enhancer rule for sdLDL-C, accuracy of the modified equation was higher than the original equation in validation set (90.47% vs. 89.73%). The estimated sdLDL-C identified an additional proportion of high-risk individuals in BHMC (4.93%) and CHARLS (1.84%).</p><p><strong>Conclusion: </strong>The newly developed equation in our study provided an accurate tool for estimating sdLDL-C level among the Chinese population as a potential cardiovascular risk-enhancer.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"366"},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between cardiorenal syndrome and depressive symptoms among the US population: a mediation analysis via lipid indices.","authors":"Guangzan Yu, Lulu Liu, Qian Ma, Hua He","doi":"10.1186/s12944-024-02356-x","DOIUrl":"10.1186/s12944-024-02356-x","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases (CVD), chronic kidney disease (CKD), and lipids are positively correlated with the presence of depressive symptoms. However, investigation into the complex link that exists between cardiorenal syndrome (CRS) and lipid indices and depression remains scarce.</p><p><strong>Methods: </strong>This study analyzed data from 11, 729 adults in the National Health and Nutritional Examination Surveys from 2005 to 2018. Weighted regression analysis was employed to examine the relationships between CRS and depression, CRS and the Patient Health Questionnaire-9 score, and lipid indices with depression. The restricted cubic spline analysis was used to determine whether there is a linear association between lipid indices and depression. Smooth curve fitting was employed to illustrate the relationship between lipids, depression, and cardiorenal diseases. Subgroup and sensitivity analyses were also conducted to enhance the stability of the results. Finally, we applied mediation analysis to explore whether the Atherogenic Index of Plasma (AIP), triglyceride glucose (TyG) index, and remnant cholesterol (RC) mediate the association between CRS and depression.</p><p><strong>Results: </strong>After applying propensity score matching (PSM), 1,509 adults remained in the study. After PSM, more remarkable results were rendered that CRS was associated with depression compared with non-CRS (OR: 1. 240, 95% CI: 1. 237 ~ 1. 243), only-CVD (OR: 0. 646, 95% CI: 0. 644 ~ 0. 649), and only-CKD (OR: 1.432, 95% CI: 1.428 ~ 1.437) in a fully corrected model. Smooth curve fitting shows that the intersection point of the lines of CRS and non-CRS occurs at a higher value on the horizontal axis than the intersection point of the lines representing CVD and non-CVD. In the fully corrected model, AIP, TyG, and RC did not independently mediate the association between CRS and depression.</p><p><strong>Conclusion: </strong>There was a significant association between CRS and depression and a linear relationship between AIP, TyG, and RC and depression. However, the above lipid indicators did not mediate the association between CRS and depression.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"365"},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Plasma lipids and glycaemic indices in Australians following plant-based diets versus a meat-eating diet.","authors":"Grace Austin, Jessica J A Ferguson, Shaun Eslick, Christopher Oldmeadow, Lisa G Wood, Manohar L Garg","doi":"10.1186/s12944-024-02362-z","DOIUrl":"10.1186/s12944-024-02362-z","url":null,"abstract":"","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"364"},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association analysis of gut microbiota with LDL-C metabolism and microbial pathogenicity in colorectal cancer patients.","authors":"Mingjian Qin, Zigui Huang, Yongqi Huang, Xiaoliang Huang, Chuanbin Chen, Yongzhi Wu, Zhen Wang, Fuhai He, Binzhe Tang, Chenyan Long, Xianwei Mo, Jungang Liu, Weizhong Tang","doi":"10.1186/s12944-024-02333-4","DOIUrl":"10.1186/s12944-024-02333-4","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression.</p><p><strong>Methods: </strong>This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms.</p><p><strong>Results: </strong>The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically.</p><p><strong>Conclusions: </strong>The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"367"},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the associations and potential mediators between lipid biomarkers and the risk of developing gout: NHANES 2007-2018.","authors":"Yuzhe Huang, Ying Li, Zhounan Wu, Yuhang Liang, Jinshen He","doi":"10.1186/s12944-024-02346-z","DOIUrl":"10.1186/s12944-024-02346-z","url":null,"abstract":"<p><strong>Background: </strong>Gout stands as a prevailing manifestation of inflammatory arthritis. While it is linked to several well-established risk factors, the associations between lipid profiles and the risk of gout remain unclear.</p><p><strong>Methods: </strong>This research involved National Health and Nutrition Examination Survey data (2007-2018). The cardiometabolic index, which incorporates the Triglycerides (TG)/High-density lipoprotein cholesterol (HDL) ratio and waist to height ratio (WHtR), was used to assess lipid profiles and metabolic health. Multivariate logistic regression analysis, propensity score matching, and mediation analyses were utilized to evaluate the associations of lipid profiles and the cardiometabolic index with the risk of developing gout.</p><p><strong>Results: </strong>Among 11,032 participants, each 1-unit increase in TG levels was associated with a 65% increase in the odds of developing gout before matching [1.65 (1.15-2.38), P = 0.007] and a 155% increase in the odds of developing gout after matching [2.55 (1.59-4.09), P = 0.007]. Each 1-unit increase in the cardiometabolic index was linked to an 81% increase in the odds of developing gout before matching [1.81 (1.22-2.70), P = 0.004] and a 215% increase in the odds of developing gout after matching [3.15 (1.84-5.40), P < 0.001]. The participants with HDL levels in the third quartile presented a 35% reduction in gout risk relative to those with HDL levels in the first quartile before matching [0.65 (0.46-0.92), P = 0.014] and a 51% reduction in gout risk after matching [0.49 (0.32-0.75), P < 0.001]. Mediation analyses revealed that BMI, WHtR, and homeostatic model assessment for insulin resistance (HOMA-IR) mediated the relationships between TG levels and the risk of developing gout at 18.75%, 24.28%, and 5.35%, respectively. For the association between HDL levels and the risk of developing gout, the mediating effects of BMI, WHtR, leukocytes, γ-glutamyltransferase (in those with HDL < 56 mmol/L), and HOMA-IR were 57.98%, 69.03%, 8.77%, 5.18%, and 11.14%, respectively.</p><p><strong>Conclusion: </strong>This study reveals the relationship between lipid profiles and the risk of developing gout. Regularly checking TG and HDL levels and actively managing obesity, insulin resistance, oxidative stress and inflammation are important for lowering the risk of developing gout.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"363"},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of fructose-induced hepatic lipid accumulation by vitamin D₃ supplementation and high-intensity interval training in male Sprague‒Dawley rats.","authors":"Behnaz Shokri, Hamid Mohebbi, Javad Mehrabani","doi":"10.1186/s12944-024-02347-y","DOIUrl":"10.1186/s12944-024-02347-y","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic lipid accumulation (IHL), a hallmark of metabolic disorders, is closely associated with de novo lipogenesis (DNL). Notably, fructose feeding increased the DNL. Lifestyle modifications resulting from dietary changes and increased physical activity/exercise can decrease the IHL content. We examined the effects of vitamin D₃ supplementation (VDS), high-intensity interval training (HIIT), and their combination on the transcription factors and enzymes of the DNL pathway in male Sprague‒Dawley rats fed a high-fructose diet (HFrD).</p><p><strong>Methods: </strong>Forty male rats were assigned to 5 groups (n = 8): CS (the control group had a standard diet); CF (the control group had HFrD (10% (w/v) fructose solution in tap water)); and FT (HFrD + HIIT: 10 bouts of 4 min of high-intensity running, corresponding to 85-90% of the maximal speed with 2 min active rest periods of 50% maximal speed, 5 days per week); FD (HFrD + intervention of intraperitoneal injection of 10000 IU/kg/week VDS); FTD (HFrD + HIIT + VDS) that were maintained for 12 weeks. ELISA, the GOD-POD assay, folch, western blotting, and oil red O staining were used to determine insulin, fasting blood glucose (FBG), hepatic triglyceride (TG) and cholesterol levels; SREBP1c, ChREBP-β, ACC1, FASN, p-ACC1, AMPK, p-AMPK, and PKA protein expression; and IHL content, respectively.</p><p><strong>Results: </strong>Both HIIT and VDS led to significant increases in the levels of PKA, AMPK, p-AMPK, and p-ACC1, as well as significant decreases in the levels of SREBP1c, ChREBP-β, ACC1, FASN, insulin, FBG, liver TG, liver cholesterol, and IHL. HIIT exhibited superior efficacy over VDS in reducing ChREBP-β, ACC1, insulin, FBG, liver TG and cholesterol, as well as increasing p-ACC1 and PKA. Notably, the combined intervention of HIIT and VDS yielded the most substantial improvements across all the parameters.</p><p><strong>Conclusions: </strong>HFrD causes IHL accumulation and the onset of diabetes, whereas VDS and HIIT, along with their combined effects, prevent the consequences of HFrD.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"362"},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic immune-inflammation mediates the association between Klotho protein and metabolic syndrome: findings from a large-scale population-based study.","authors":"Yongzhou Liang, Ying Liu, Qin Tan, Kaiyu Zhou, Yurong Wu, Li Yu","doi":"10.1186/s12944-024-02339-y","DOIUrl":"10.1186/s12944-024-02339-y","url":null,"abstract":"<p><strong>Background: </strong>This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome.</p><p><strong>Methods: </strong>This study enrolled 13,119 participants aged 40-79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome.</p><p><strong>Results: </strong>The study participants had an average age of 56.06 years (95% CI: 55.76-56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50-980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70-0.97), hypertension (OR: 0.83, 95% CI: 0.70-0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67-0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome.</p><p><strong>Conclusion: </strong>The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"23 1","pages":"360"},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}