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* ; Adult ; Nutrition Surveys ; Intra-Abdominal Fat ; Lipid Accumulation Product ; Middle Aged ; Obesity, Abdominal/complications* ; Adiposity ; Risk Factors ; Logistic Models

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

OBJECTIVES: To explore the association between Chinese visceral adiposity index (CVAI) and the risk of nephrolithiasis. METHODS: This cross-sectional study analyzed data from 78 438 Chinese adults who underwent ultrasound examinations during health screening at the Health Examination Center of Affiliated Hospital of Yangzhou University. Participants were divided into quartiles (Q1-Q4 groups) based on CVAI. Multivariate logistic regression models were utilized to evaluate the association between CVAI and nephrolithiasis risk, followed by subgroup analyses to further explore potential relationships. The performance of CVAI in predicting the risk of nephrolithiasis was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Increased CVAI was significantly associated with a higher risk of nephrolithiasis, with prevalence rising from 3.36% in the Q1 group to 10.67% in the Q4 group (P<0.01). In adjusted models, CVAI was positively correlated with the prevalence rate of nephrolithiasis (OR=1.002, 95%CI: 1.001-1.004, P<0.01). The risks of nephrolithiasis in the Q2, Q3, and Q4 groups were 1.196-fold (95%CI: 1.069-1.338, P<0.01), 1.260-fold (95%CI: 1.109-1.433, P<0.01), and 1.316-fold (95%CI: 1.125-1.539, P<0.01) higher than in the Q1 group, respectively. Subgroup analysis revealed that CVAI was positively associated with the risk of nephrolithiasis in male participants, individuals aged <60 years, the hypertension group, populations with or without diabetes mellitus, and the normal body mass index subgroup. Genders and age had an interaction effect on the correlation between CVAI and the risk of nephrolithiasis development (both P<0.05). The ROC curve analysis demonstrated that CVAI exhibited superior predictive efficacy compared to waist circumference, body mass index, visceral adiposity index, weight-adjusted waist index, cardiometabolic index and body shape index, with an area under the curve of 0.622. CONCLUSIONS In Chinese adults, CVAI is positively associated with the risk of nephrolithiasis development, which may serve as a potential predictive marker for nephrolithiasis.
Humans ; Nephrolithiasis/etiology* ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; Intra-Abdominal Fat ; Risk Factors ; China/epidemiology* ; Adiposity ; Aged ; Logistic Models ; Obesity, Abdominal/epidemiology* ; East Asian People

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

Humans ; Intra-Abdominal Fat/diagnostic imaging* ; Coronary Artery Disease ; Body Mass Index

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1β, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.
Mice ; Animals ; Adipose Tissue, Brown ; Molecular Docking Simulation ; PPAR alpha/metabolism* ; Adipose Tissue, White ; RNA, Messenger/metabolism*

Objective: To explore abdominal fat mass distribution and contents among obese children via magnetic resonance imaging (MRI), and analyze the correlations of abdominal adipose tissue with anthropometric and metabolic parameters. Methods: Cross-sectional study. There were 60 obese children admitted to the Children's Health Care Department and Endocrinology Department at Children's Hospital of Nanjing Medical University from July 2016 to December 2018. Children's gender, age, height, weight, body composition, waist circumference and blood pressure were recorded. The levels of fasting blood glucose, lipids, insulin were measured, and liver ultrasound was performed, and the body mass index Z score (BMI-Z), waist-to-height ratio (WHtR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. In addition, contents of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) were calculated according to feedback of abdominal MRI scan images. The associations between the contents of abdominal adipose tissue, physical examination status and metabolic disorders among obese children were analyzed through correlation analysis and regression analysis. Receiver operating characteristic (ROC) curve was used to compare the accuracy of fat mass in different parts of the abdomen in predicting their metabolic disorders. Results: A total of 60 children were enrolled in the study, included 44 boys and 16 girls, with age of (9.2±1.4) years. The contents of SAT, VAT and TAAT among the 60 children were positively associated with BMI-Z (r=0.60, 0.46, 0.59), body fat percentage (r=0.64, 0.67, 0.68) and waist-to-height ratio (r=0.60, 0.57, 0.61) (all P<0.01). Meanwhile, contents of SAT and TAAT were also positively correlated with systolic blood pressure (r=0.47, 0.49), triglyceride (r=0.33, 0.35) and HOMA-IR (r=0.33, 0.28)(all P<0.05). In order to adjust the confounding effects among various variables, regression analysis was applied and the result showed that the body fat percentage (β=0.59, 0.66, 0.65) and waist-to-height ratio (β=0.53, 0.63, 0.59) were most related to abdominal fat contents (all P<0.01), including SAT, VAT and TAAT among obese children. According to ROC, SAT had outstanding evaluation performances for the diagnosis of insulin resistance and metabolic syndrome, while VAT had excellent evaluation performances for non-alcoholic fatty liver disease (area under curve=0.68, 0.69, 0.69, 95%CI 0.54-0.82, 0.55-0.84, 0.53-0.85, P=0.017, 0.014, 0.019). Conclusions: As one of the best indexes, body fat percentage and WHtR can be used to predict the contents of SAT, VAT and TAAT among obese children. With the increase of abdominal SAT or VAT, the risks for insulin resistance, metabolic syndrome and non-alcoholic fatty liver disease would increase. Assessment of abdominal fat and metabolic risks in obese children should combine BMI-Z with waist circumference and body composition analysis.
Abdominal Fat/metabolism* ; Body Mass Index ; Child ; Cross-Sectional Studies ; Female ; Humans ; Insulin Resistance ; Magnetic Resonance Imaging ; Male ; Metabolic Diseases/metabolism* ; Metabolic Syndrome/metabolism* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/metabolism*

BACKGROUND: Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders. METHODS: Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders. RESULTS: In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups. CONCLUSIONS Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.
Adipose Tissue ; Animals ; Diet, High-Fat/adverse effects* ; Insulin Resistance ; Liver ; Male ; Mice ; Mice, Inbred C57BL ; Obesity ; Subcutaneous Fat