1.Natural diosmin alleviating obesity and nonalcoholic fatty liver disease by regulating the activating the AMP-activated protein kinase (AMPK) pathway.
Can LIU ; Siyu HAO ; Mengdi ZHANG ; Xueyu WANG ; Baiwang CHU ; Tingjie WEN ; Ruoyu DANG ; Hua SUN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):863-870
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage*
;
Animals
;
AMP-Activated Protein Kinases/genetics*
;
Humans
;
Non-alcoholic Fatty Liver Disease/enzymology*
;
Mice
;
Obesity/enzymology*
;
Hep G2 Cells
;
Male
;
3T3-L1 Cells
;
Mice, Inbred C57BL
;
Signal Transduction/drug effects*
;
Lipid Metabolism/drug effects*
;
Chrysanthemum/chemistry*
;
Lipogenesis/drug effects*
2.Hydrogen Sulfide Alleviates Lipid Peroxidation-Mediated Carbonyl Stress in Uranium-Intoxicated Kidney Cells via Nrf2/ARE Signaling.
Jia Lin LIU ; Min WANG ; Rui ZHANG ; Ji Fang ZHENG ; Xi Xiu JIANG ; Qiao Ni HU
Biomedical and Environmental Sciences 2025;38(4):484-500
OBJECTIVE:
To explore the protective effects and underlying mechanisms of H 2S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.
METHODS:
Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression.
RESULTS:
GYY4137 (an H 2S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability.
CONCLUSION
H 2S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H 2S axis. Simultaneously, the Nrf2-controlled CBS/H 2S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H 2S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
NF-E2-Related Factor 2/genetics*
;
Animals
;
Hydrogen Sulfide/pharmacology*
;
Rats
;
Signal Transduction/drug effects*
;
Lipid Peroxidation/drug effects*
;
Cell Line
;
Uranium/toxicity*
;
Antioxidant Response Elements
;
Kidney/metabolism*
;
Oxidative Stress/drug effects*
;
Cell Survival/drug effects*
;
Apoptosis/drug effects*
3.Regulatory roles of DGAT and PDAT genes in plant oil synthesis.
Yang WU ; Mengjuan LIU ; Youning WANG ; Dexiao LI ; Yuhua YANG ; Tingjun ZHANG ; Huiwen ZHOU
Chinese Journal of Biotechnology 2025;41(1):216-229
There is a large gap between production and demand of plant oil in China, which leads to the heavy reliance on imports. Diacylglycerol acyltransferase (DGAT) and phospholipid: diacylglycerol acyltransferase (PDAT) are two key enzymes responsible for the synthesis of triacylglycerol, thereby affecting the yield and quality of plant oil. This paper comprehensively reviews the research progress in DGAT and PDAT in terms of their biological functions in plant oil synthesis, the molecular mechanisms of regulating plant lipid metabolism, growth, and development under stress, and their roles in driving oil synthesis under the background of synthetic biology. Furthermore, future research and application of DGAT and PDAT are prospected. This review aims to provide a basis for deeply understanding the molecular mechanism of plant oil synthesis and improving the quality and productivity of oil crops by the utilization of DGAT and PDAT genes.
Diacylglycerol O-Acyltransferase/physiology*
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Plant Oils/metabolism*
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Acyltransferases/metabolism*
;
Lipid Metabolism/genetics*
;
Gene Expression Regulation, Plant
;
Triglycerides/biosynthesis*
4.Effect of heterologous expression of Scenedesmus quadricauda malic enzyme gene SqME on photosynthetic carbon fixation and lipid accumulation in tobacco leaves.
Yizhen LIU ; Mengyuan LI ; Zhanqian LI ; Yushuang GUO ; Jingfang JI ; Wenchao DENG ; Ze YANG ; Yan SUN ; Chunhui ZHANG ; Jin'ai XUE ; Runzhi LI ; Chunli JI
Chinese Journal of Biotechnology 2025;41(7):2829-2842
Microalgae possess high photosynthetic efficiency, robust adaptability, and substantial biomass, serving as excellent biological resources for large-scale cultivation. Malic enzyme (ME), a ubiquitous metabolic enzyme in living organisms, catalyzes the decarboxylation of malate to produce pyruvate, CO2, and NAD(P)H, playing a role in multiple metabolic pathways including energy metabolism, photosynthesis, respiration, and biosynthesis. In this study, we identified the Scenedesmus quadricauda malic enzyme gene (SqME) and its biological functions, aiming to provide excellent target genes for the genetic improvement of higher plants. Based on the RNA-seq data from S. quadricauda under the biofilm cultivation mode with high CO2 and light energy transfer efficiency and small water use, a highly expressed gene (SqME) functionally annotated as ME was cloned. The physicochemical properties of the SqME-encoded protein were systematically analyzed by bioinformatics tools. The subcellular localization of SqME was determined via transient transformation in Nicotiana benthamiana leaves. The biological functions of SqME were identified via genetic transformation in Nicotiana tabacum, and the potential of SqME in the genetic improvement of higher plants was evaluated. The ORF of SqME was 1 770 bp, encoding 590 amino acid residues, and the encoded protein was located in chloroplasts. SqME was a NADP-ME, with the typical structural characteristics of ME. The ME activity in the transgenic N. tabacum plant was 1.8 folds of that in the wild-type control. Heterologous expression of SqME increased the content of chlorophyll a, chlorophyll b, and total chlorophyll by 20.9%, 26.9%, and 25.2%, respectively, compared with the control. The transgenic tobacco leaves showed an increase of 54.0% in the fluorescence parameter NPQ and a decrease of 30.1% in Fo compared with the control. Moreover, the biomass, total lipids, and soluble sugars in the transgenic tobacco leaves enhanced by 20.5%, 25.7%, and 9.5%, respectively. On the contrary, the starch and protein content in the transgenic tobacco leaves decreased by 22.4% and 12.2%, respectively. Collectively, the SqME-encoded protein exhibited a strong enzymatic activity. Heterologous expressing of SqME could significantly enhance photosynthetic protection, photosynthesis, and biomass accumulation in the host. Additionally, SqME can facilitate carbon metabolism remodeling in the host, driving more carbon flux towards lipid synthesis. Therefore, SqME can be applied in the genetic improvement of higher plants for enhancing photosynthetic carbon fixation and lipid accumulation. These findings provide scientific references for mining of functional genes from S. quadricauda and application of these genes in the genetic engineering of higher plants.
Nicotiana/genetics*
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Photosynthesis/physiology*
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Malate Dehydrogenase/biosynthesis*
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Plant Leaves/genetics*
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Scenedesmus/enzymology*
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Carbon Cycle/genetics*
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Lipid Metabolism/genetics*
;
Plants, Genetically Modified/metabolism*
5.Chronic prostatitis/chronic pelvic pain syndrome induces metabolomic changes in expressed prostatic secretions and plasma.
Fang-Xing ZHANG ; Xi CHEN ; De-Cao NIU ; Lang CHENG ; Cai-Sheng HUANG ; Ming LIAO ; Yu XUE ; Xiao-Lei SHI ; Zeng-Nan MO
Asian Journal of Andrology 2025;27(1):101-112
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans
;
Male
;
Prostatitis/blood*
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Adult
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Pelvic Pain/blood*
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Metabolomics
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Prostate/metabolism*
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Middle Aged
;
Chronic Pain/blood*
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Metabolome
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Case-Control Studies
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Tryptophan/blood*
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Depression/blood*
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Oxidative Stress/physiology*
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Chronic Disease
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Lipid Metabolism/physiology*
6.Pachymic acid promotes brown/beige adipocyte differentiation and lipid metabolism in preadipocytes.
Kunling CHEN ; Xiaobing DOU ; Yiyou LIN ; Danyao BAI ; Yangzhou LUO ; Liping ZHOU
Journal of Zhejiang University. Medical sciences 2025;54(3):333-341
OBJECTIVES:
To investigate the effect of pachymic acid on brown/beige adipocyte differentiation and lipid metabolism in preadipocytes.
METHODS:
3T3-L1 MBX cells were induced to differentiate into beige adipocytes using a brown cocktail method. The impact of pachymic acid on the viability of 3T3-L1 MBX cells was evaluated using the CCK-8 assay. The formation of lipid droplets following treatment with pachymic acid was observed by oil red O staining. The mRNA expression levels of key browning genes, including uncoupling protein (Ucp) 1, the peroxisome proliferator activated receptor-γ coactivator (Pgc)-1α, and the PR domain-containing protein 16 (Prdm16), as well as the mRNA expression of sterol regulatory element-binding protein (Srebp) 1c, acetyl-coA carboxylase (Acc), fatty acid synthase (Fas), and hormone-sensitive triglyceride lipase (Hsl), adipose triglyceride lipase (Atgl), and carnitine palmitoyltransferase (Cpt) 1 were detected by quantitative reverse transcription polymerase chain reaction. The protein expression of Ucp1, Pgc-1a, and Prdm16 was detected by Western blotting.
RESULTS:
The 3T3-L1 MBX cells were induced in vitro to form beige adipocytes with high expression of key browning genes(Ucp1, Pgc-1α, and Prdm16), and beige adipose-marker genes (Cd137, Tbx1, and Tmem26). Concentrations range of 0-80 μmol/L pachymic acid were non-cytotoxic to 3T3-L1 MBX cells. Pachymic acid treatment significantly inhibited the differentiation of 3T3-L1 MBX cells, resulting in a notable decrease in lipid accumulation. There was a marked increase in the expression of key browning genes and their proteins products, such as Ucp1, Pgc-1α, and Prdm16, while the expressions of fat synthesis-related genes Srebp1c, Acc and Fas were significantly decreased (all P<0.05). The expressions of lipolysis-related genes (Hsl, Atgl, and Cpt1) were significantly increased (all P<0.05). Treatment with 20 μmol/L pachymic acid showed the most pronounced effect.
CONCLUSIONS
Pachymic acid can inhibit fat synthesis and promote lipid decomposition by regulating the brown formation and lipid differentiation of preadipocytes.
Animals
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Lipid Metabolism/drug effects*
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Mice
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Cell Differentiation/drug effects*
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Adipocytes, Beige/drug effects*
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3T3-L1 Cells
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Adipocytes, Brown/drug effects*
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Triterpenes/pharmacology*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Uncoupling Protein 1
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Sterol Regulatory Element Binding Protein 1/metabolism*
7.Research progress on glycolipid metabolism of Sertoli cell in the development of spermatogenic cell.
Shuhao LI ; Liang KONG ; Jingyan LIANG ; Tan MA
Journal of Zhejiang University. Medical sciences 2025;54(2):257-265
Sertoli cells play an important role in the process of spermatogenesis, and the abnormalities in spermatogenesis are closely related to disruptions in glycolipid metabolism. The metabolic environment of Sertoli cells is hypoxic, with glycolysis and fatty acid β-oxidation being the primary metabolic pathways. In Sertoli cells, glycolysis produces lactate to provide energy for spermatogenic cells, while fatty acid β-oxidation generates ATP. Currently, the relationship between glycolipid metabolism in Sertoli cells and spermatogenic cell development, as well as the interplay between glucose and lipid metabolism remain unclear. Various hormones, including sex hormones, can affect glucose metabolism in Sertoli cells by endocrine regulation. The activation or inhibition of signaling pathways such as AMPK, mTOR, and Akt can alter the expression levels of glycolysis-related transporter genes and the synthesis of fatty acids, thereby affecting glycolipid metabolism in Sertoli cells. Some transcription factors such as PPARγ can regulate downstream fatty acid metabolism-related genes by directly binding to their response elements and promoting the oxidation of fatty acids in Sertoli cells. In this article we elaborate on the key factors influencing glycolipid metabolism in Sertoli cells and their interconnections, as well as their potential clinical implications, offering new insights for precisely targeted treatments of male infertility.
Sertoli Cells/cytology*
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Male
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Glycolipids/metabolism*
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Spermatogenesis/physiology*
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Humans
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Lipid Metabolism
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Animals
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Fatty Acids/metabolism*
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Signal Transduction
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Glycolysis
8.The role of polyunsaturated fatty acid lipid peroxidation in ferroptosis after intracerebral hemorrhage: a review of mecha-nisms and therapeutic implications.
Man GUO ; Guohui ZHAO ; Zhibiao CAI ; Zhenyu ZHANG ; Jie ZHOU
Journal of Zhejiang University. Medical sciences 2025;54(5):694-704
Ferroptosis, a regulated cell death process distinct from apoptosis, is characterized by iron dysregulation and reactive oxygen species (ROS) accumulation. After intracerebral hemorrhage (ICH), decreased cerebral blood flow and iron released from erythrocytes trigger lipid peroxidation-particularly of polyunsaturated fatty acids (PUFAs)-through a cascade of reactions in local brain tissues, promoting ferroptosis. Mitochondrial dysfunction and neuroinflammation further elevate ROS, exacerbating lipid peroxidation and accelerating neuronal ferroptosis. Thus, PUFA peroxidation and associated metabolic pathways play a critical role in ICH-related neuronal damage. This review summarizes current understanding of how PUFA peroxidation contributes to ferro-ptosis after ICH, discusses key regulatory mechanisms involving lipid and iron metabolism, and highlights potential therapeutic strategies targeting ferroptosis to improve neurological outcomes.
Ferroptosis/physiology*
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Humans
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Cerebral Hemorrhage/pathology*
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Lipid Peroxidation
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Fatty Acids, Unsaturated/metabolism*
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Reactive Oxygen Species/metabolism*
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Iron/metabolism*
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Animals
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Mitochondria/metabolism*
9.Efficacy of "Biaoben acupoint compatibility" moxibustion for abdominal obesity and its effect on lipid accumulation.
Chengwei FU ; Lihua WANG ; Xia CHEN ; Yanji ZHANG ; Yingrong ZHANG ; Wei HUANG ; Hua WANG ; Zhongyu ZHOU
Chinese Acupuncture & Moxibustion 2025;45(5):614-619
OBJECTIVE:
To observe the efficacy of "Biaoben acupoint compatibility" moxibustion for abdominal obesity and its effect on blood lipid, lipid accumulation product (LAP) and cardiometabolic index (CMI).
METHODS:
A total of 150 patients with abdominal obesity were randomly divided into an observation group (75 cases, 5 cases dropped out) and a control group (75 cases, 6 cases dropped out). The control group received lifestyle guidance. The observation group received "Biaoben acupoint compatibility" moxibustion at Zhongwan (CV12), Guanyuan (CV4) and bilateral Tianshu (ST25), Zusanli (ST36) on the basis of the control group, 20 min each time, once every other day, 3 times a week for 8 weeks. Before and after treatment, the waist circumference, hip circumference, weight, body mass index (BMI) were observed, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the LAP and CMI were calculated in the two groups.
RESULTS:
After treatment, the waist circumference, weight and BMI were decreased compared with those before treatment in both groups (P<0.05), the changes of the above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the hip circumference, TC level, TG level, LAP and CMI in the observation group were decreased compared with those before treatment (P<0.05), the HDL-C level was increased compared with that before treatment (P<0.05);the changes of the TC level, TG level, LAP, CMI and HDL-C level in the observation group were larger than those in the control group (P<0.05).
CONCLUSION
"Biaoben acupoint compatibility" moxibustion can reduce the degree of obesity in patients with abdominal obesity, and improve blood lipid and reduce lipid accumulation.
Humans
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Acupuncture Points
;
Moxibustion
;
Male
;
Female
;
Middle Aged
;
Obesity, Abdominal/blood*
;
Adult
;
Lipids/blood*
;
Lipid Metabolism
;
Triglycerides/blood*
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Young Adult
;
Treatment Outcome
;
Aged
10.Association of lipid accumulation product, visceral adiposity index and endometriosis: A cross-sectional study from the 1999-2006 NHANES.
Yue HOU ; Yingyi GUO ; Jinshuang WU ; Ning LOU ; Dongxia YANG
Annals of the Academy of Medicine, Singapore 2025;54(10):605-615
INTRODUCTION:
Endometriosis (EMS) is a common gynaecological disorder linked to metabolic disturbances. However, evidence on the associations between lipid accumulation product (LAP) and visceral adiposity index (VAI) with the risk of EMS remains limited. This study aimed to explore the potential associations between LAP, VAI and EMS.
METHOD:
Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES), including a total of 2046 samples. Weighted multivariable logistic regression models and smoothed curve fitting were used to assess the associations between LAP, VAI and EMS. Additionally, subgroup analyses and interaction tests were conducted to evaluate intergroup differences in the associations between LAP, VAI and EMS.
RESULTS:
In the fully adjusted model, higher Log2 LAP (odds ratio [OR] 1.256, 95% confidence interval [CI] 1.102-1.431, P=0.0014) and Log2 VAI (OR 1.287, 95% CI 1.105-1.498, P=0.0022) were significantly associated with increased EMS risk. Participants in the highest quartile of Log2 LAP (OR 1.983, P=0.0029) and Log2 VAI (OR 1.690, P=0.0486) had a higher risk of EMS. Subgroup analysis showed stronger associations among women with diabetes (Log2 LAP OR 3.681, P=0.009; Log2 VAI OR 4.849, P=0.041).
CONCLUSION
Elevated LAP and VAI were independently associated with an increased risk of EMS. LAP and VAI may serve as potential indicators for assessing EMS-related risk, suggesting that visceral obesity and lipid metabolic disturbances might play roles in the pathophysiological process of EMS. These findings underscore the potential of LAP and VAI as non-invasive markers for EMS risk, warranting further validation in clinical settings.
Humans
;
Female
;
Cross-Sectional Studies
;
Endometriosis/metabolism*
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Adult
;
Nutrition Surveys
;
Intra-Abdominal Fat
;
Lipid Accumulation Product
;
Middle Aged
;
Obesity, Abdominal/complications*
;
Adiposity
;
Risk Factors
;
Logistic Models

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