The Association Between Neutrophil/High-Density Lipoprotein Cholesterol Ratio and Non-Alcoholic Fatty Liver Disease in a Healthy Population.

Objective: Non-alcoholic fatty liver disease (NAFLD) is characterized by abnormal lipid metabolism and inflammation. This study aimed to investigate the relationship between neutrophil-HDL cholesterol ratio (NHR) and NAFLD in a healthy population. Methods: 1881 healthy people who underwent a physical examination from August to December 2023 at the Hebei General Hospital were chosen for this cross-sectional study. 936 individuals were ultimately included thanks to propensity matching and exclusion criteria. Ultrasound was used to diagnose fatty liver and a t-test or Mann-Whitney test was used to compare the clinical characteristics of participants between groups with and without fatty liver. Logistic regression was used to construct a new model that included NHR. The predictive value of NHR as well as the new model for NAFLD in a healthy population was assessed using logistic regression and subject work characteristic curves. Results: NHR levels were higher among participants in the NAFLD group than those without NAFLD(P<0.05). NHR is a risk factor for NAFLD in a healthy population(P<0.05). The odds ratios (ORs) of NHR for predicting NAFLD in Model I (adjusted for sex, age, and BMI) and Model II (adjusted for sex, age, BMI, HbA1c, TC, TG, and ALT) were 1.166 (1.022, 1.331) and 1.248 (1.110, 1.402)(P<0.05). The new model created by logistic regression predicted NAFLD with an area under the curve of 0.676 (0.645, 0.706). Compared to participants in the low NHR group, the high NHR group exhibited a higher prevalence of NAFLD(p<0.05). Conclusion: NHR is associated with NAFLD, which is a good predictor of NAFLD in a healthy population.

The Combination of Remnant Cholesterol and Waist Circumference Offers Predictive Value for Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study from a Medical Examination Center.

Objective: To explore the association between levels of remnant cholesterol (RC) and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population, ultimately leading to the assessment of a novel proposed model combining RC and waist circumference (R-W) as a predictor of NAFLD incidence. Methods: A cross-sectional analysis was conducted of 4913 subjects undergoing physical examinations at Hebei General Hospital, with ultrasound findings being used to classify patients into individuals with and without NAFLD. Median RC values were used to separate subjects into those with low and high levels of RC, after which the predictive performance of RC and the novel R-W model when used to assess NAFLD risk was assessed through multifactorial logistic regression analyses and receiver operating characteristic curves. Results: Subjects exhibiting higher RC levels were found to exhibit an elevated risk of NAFLD incidence with or without adjusting for confounding factors. The binary logistic regression analysis-based R-W model may thus offer utility as a tool to gauge the risk of NAFLD in the general population, as it outperformed RC or WC alone, particularly when assessing women or individuals < 45 years of age. The area under the ROC curve for this combined R-W model was 0.813 (0.802, 0.824), with respective sensitivity and specificity values of 83.86% and 63.91%, all of which were significantly higher than corresponding values for RC and WC (P < 0.001). Conclusion: The present supports a strong association between RC levels and NAFLD in the general populace, and the combined R-W model exhibits greater utility as a tool to predict NAFLD incidence relative to RC or WC in isolation, particularly for individuals who are female or <45 years old.

Correlation Between Fibrinogen/Albumin and Diabetic Peripheral Neuropathy.

Purpose: This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN). Patients and Methods: A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV). Results: The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94±1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P<0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c. Conclusion: The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients.

The Relationship Between Non-HDL-C /HDL-C Ratio (NHHR) and Vitamin D in Type 2 Diabetes Mellitus.

Purpose: The objective of this research was to examine the relationship between non-HDL cholesterol/HDL cholesterol ratio (NHHR) and vitamin D in type 2 diabetes mellitus (T2DM). Patients and Methods: This study enrolled 617 T2DM participants. Participants were separated into two groups: no vitamin D deficiency and vitamin D deficiency. Participants were split into two categories: individuals who had a high NHHR and those with a low NHHR, with the median NHHR serving as the cut-off. Eventually, the study participants were classified into two groups by gender, which were further classified into vitamin D deficient and non-vitamin D deficient groups. Results: NHHR values were substantially greater in vitamin D deficient group than in the non-deficient group in both male and female T2DM patients (P<0.05). The high NHHR group displayed substantially lower vitamin D levels than the low NHHR group [16.21 (12.55,21.35) vs 19.05 (14.59,24.07), P<0.001]. NHHR was discovered to be negatively and independently associated with vitamin D levels, and there was no sex difference. Conclusion: For the first time, our research revealed a negative relationship between NHHR and vitamin D in patients with T2DM.

Mechanisms of Small Intestine Involvement in Obesity-Induced Atherosclerosis.

Purpose: Studies have shown that atherosclerotic plaques are associated with changes in the microbial composition of the intestinal flora and obesity, and that the small intestine plays an irreplaceable role in regulating intestinal flora homeostasis, but the role of the small intestine in the development of obesity-related atherosclerosis remains understudied. Therefore, this study explores the role of the small intestine in obesity-induced atherosclerosis and its molecular mechanisms. Methods: In the GSE59054 data, small intestine tissue samples from 3 normal and 3 obese mice were analyzed using bioinformatics methods. Screening for differentially expressed genes (DEGs) using the GEO2R tool. The DEGs were next processed for bioinformatics analysis. We constructed an obese mouse model and measured aortic arch pulse wave velocity (PWV). Aortic and small intestine tissues were stained with hematoxylin-eosin (HE) to observe pathological changes. Finally, immunohistochemistry was performed to verify the expression of small intestinal proteins. Results: We identified a total of 122 DEGs. Pathway analysis revealed that BMP4, CDH5, IL1A, NQO1, GSTM1, GSTA3, CAV1 and MGST2 were mainly enriched in the Fluid shear stress and atherosclerosis pathway. In addition, BMP4, NQO1 and GSTM1 are closely related to atherosclerosis. Ultrasound and pathological findings suggest the presence of obesity atherosclerosis. Immunohistochemistry verified high expression of BMP4 and low expression of NQO1 and GSTM1 in obese small intestine tissues. Conclusion: The altered expression of BMP4, NQO1 and GSTM1 in small intestine tissues during obesity may be related to atherosclerosis, and Fluid shear stress and atherosclerosis pathway may be the molecular mechanism of their role.

Effect of semaglutide and empagliflozin on cognitive function and hippocampal phosphoproteomic in obese mice.

Objective: Based on the 4D label-free phosphoproteomic technique, we examined the differences in cognitive function and hippocampal phosphorylated protein expression in high-fat diet-induced obese mice after the intervention of semaglutide and empagliflozin, as well as the effects of both on protein activity and function in obese mice's hippocampal tissues and the signaling pathways involved. Methods: Thirty-two C57BL/6JC male mice were assigned to two groups randomly: A control group (group C, 10% of energy is from fat, n = 8) and a high-fat diet group (group H, 60% of energy is from fat, n = 24). The high-fat diet-induced obese mice were screened after 12 weeks of feeding based on the criterion that the bodyweight of mice in fat rich diet group was greater than or equal to 20% of the average body weight of the mice in the blank control group. Group H separate into group H (n = 8), group Semaglutide (group S, n = 8), and group empagliflozin (group E, n = 8). For a total of 12 weeks, group S received 30 nmol/kg/d bodyweight of semaglutide intraperitoneally, group E received 10 mg/kg/d bodyweight of empagliflozin via gavage, and groups C and H received equal amounts of saline by intraperitoneal injection and gavage. At the end of treatment, the mice were appraised for cognitive function employing the Morris water maze (MWM), and serum fasting glucose, lipids, and inflammatory parameters were measured. The 4D label-free phosphoproteomics method was employed to screen the differential phosphoproteins and loci in hippocampal tissues of mice in different treatment groups, and bioinformatics was used to analyze the biological processes, signaling pathways, and related protein-protein interaction (PPI) network analysis of these differentially phosphorylated proteins. Results: In comparison to normal controls, The escape latency of obese mice induced by high-fat diet was prolonged, the percentage of swimming time in the target quadrant was reduced, and the number of times of crossing the platform was reduced, whereas semaglutide and empagliflozin treatment reduced escape latency, increase the percentage of swim time in the target quadrant and increase the frequency of passing through the platform area, although there is little difference in the effect of the two drugs. The phosphoproteomic results showed 20,493 unique phosphorylated peptides, representing 21,239 phosphorylation sites and 4,290 phosphorylated proteins. Further analysis revealed that the proteins corresponding to these differentially phosphorylated sites are jointly distributed in signaling pathways such as dopaminergic synapses and axon guidance, and are involved in biological processes such as neuronal projection development, synaptic plasticity, and axonogenesis. Notably, the key factors voltage-dependent L-type calcium channel subunit alpha-1D (CACNA1D), voltage-dependent P/Q-type calcium channel subunit alpha-1A (CACNA1A), and voltage-dependent N-type calcium channel subunit alpha-1B (CACNA1B) were all found to be involved in the dopaminergic synapse pathway, and their expression was upregulated by semaglutide and empagliflozin. Conclusion: We found for the first time that a high-fat diet decreased CACNA1D, CACNA1A, and CACNA1B protein serine phosphorylation, which may affect neuronal development, synaptic plasticity, and cognitive function in mice. Notably, semaglutide and empagliflozin increased the phosphorylation of these proteins.

Association Between Vitamin D Levels and the Atherogenic Index of Plasma Among Chinese with Type 2 Diabetes Mellitus.

Purpose: The relationship between atherogenic index of plasma (AIP) values and 25-hydroxyvitamin D (25[OH] D) was examined in type 2 diabetes mellitus (T2DM). Patients and Methods: Six hundred and ninety-eight T2DM patients were included. Patients were allocated to two groups, namely, the vitamin D-deficient and non-deficient groups (threshold of 20 ng/mL). The AIP was determined as log (TG [mmol/L] / HDL-C [mmol/L]). The patients were then allocated to two further groups according to the median AIP value. Results: AIP level in the vitamin D-deficient group was significantly higher than that in non-deficient group (P<0.05). Patients with high AIP values had markedly reduced levels of vitamin D levels compared with those in the low-AIP group [15.89 (11.97, 20.29) VS 18.22 (13.89, 23.08), P<0.001]. Patients in the high AIP group had a higher rate of vitamin D deficiency (73.3% VS 60.6%). It was found that AIP values were adversely and independently correlated with vitamin D levels. The AIP value was shown to independently predict vitamin D deficiency risk in T2DM patients. Conclusion: Patients with T2DM were shown to have an increased risk of vitamin D insufficiency when their AIP levels were low. This suggests that AIP is associated with vitamin D insufficiency in Chinese patients with type 2 diabetes.

Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice.

Purpose: Semaglutide, a new long-acting glucagon-like peptide-1 analogue, has shown benefits for renal diseases, but its direct role on kidney metabolism under obesity remains unclear. The study aims to elucidate the protective effect and metabolic modulation mechanism of semaglutide on obesity-related kidney injury. Methods: Male C57BL/6J mice were divided into control and obesity groups. Mice in the obesity group had a high-fat diet and were treated with or without semaglutide (30nmol/kg/day). The study assayed blood biochemistry and then evaluated renal pathological injury through Periodic Acid-Schiff staining and electron microscopy. Metabolomics was utilized to analyze obesity-related metabolites in kidney samples. Results: Semaglutide significantly improved glucose homeostasis, insulin resistance, and kidney injury in obese mice. We successfully identified 377 altered metabolites (P<0.05). It was suggested that semaglutide directly improved oxidative stress and inflammation-related metabolites such as nicotinamide adenine dinucleotide (NAD+) and adenosine in the kidney of obese mice, which have not been documented in obesity-related kidney injury. Relevant enriched pathways were included phospholipids and lysophospholipids metabolism, purine metabolism, NAD+ metabolism, and insulin resistance-related metabolism. They could serve as potential targets for intervention of obesity-related kidney injury. Conclusion: Our study revealed the metabolomics-based renoprotective mechanism of semaglutide in obese mice for the first time. The innovation lied in the identified metabolites such as NAD+ and adenosine targeted by semaglutide, which have not been documented in obesity-related kidney injury. Semaglutide may be a promising therapy for obesity-related kidney diseases.

Effect of high-fat diet and empagliflozin on cardiac proteins in mice.

Using proteomic techniques the impact of the sodium-glucose transport protein 2 inhibitor empagliflozin on cardiac protein expression in a mouse model was assessed under normal and high-fat diet (HFD) conditions. We examined the effect of obesity on serological markers and heart function in obese mice treated with or without empagliflozin and used proteomic techniques to investigate alterations in cardiac protein expression. Using bioinformatic techniques, data were screened for differentially expressed proteins (DEPs) implicated in the putative mechanism of empagliflozin's cardioprotective effects. In C57BL/6 mice, HFD increased body weight, blood lipid, and glucose levels and was associated with structural damage to the heart. Empagliflozin reduces body weight, improves glucose and lipid metabolism, alleviates obesity-induced cardiac ventricular wall thickening, and lowers cardiac tissue collagen. The expression of several proteins was altered in the heart, mainly related to lipid metabolism. Following empagliflozin treatment, the expression of several lipid metabolism-related proteins was considerably reduced. Further examination of DEPs revealed that following empagliflozin treatment, the expressions of Apoe, Apoc1, Saa2, Apoa2, and Pon1 altered dramatically, suggesting that these proteins may be the main proteins that empagliflozin uses to treat obesity-induced aberrant lipid metabolism. Empagliflozin may protect the heart by altering the expression of genes including Apoe, Apoc1, Saa2, Apoa2, and Pon1, which are all involved in lipid metabolism disturbance in obesity.

The Correlation Between Estimated Glucose Disposal Rate and Coagulation Indexes in Type 2 Diabetes Mellitus.

Purpose: To study the correlation between estimated glucose disposition rate (eGDR) and coagulation parameters in type 2 diabetes patients (T2DM). Materials and Methods: A total of 948 patients suffering from T2DM were enrolled for this research. Various blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were assessed. Body mass index (BMI), hypertension, and the levels of glycated hemoglobin (HbA1c) were used to calculate the patients' eGDRs. All patients were sorted into two groups: those with high eGDRs (eGDR≥7.5) and those with low eGDRs (eGDR<7.5). The patients were then separated into groups of men and women. The connection between eGDR and coagulation indexes was examined using Spearman correlation, Pearson correlation, and multiple linear regression analysis. Results: In comparison to the high-eGDR group, reduced PT and APTT levels with increased FIB levels were observed in the low-eGDR group (P =0.006, P <0.001, and P = 0.035, respectively). The eGDR showed a positive relation with APTT (r = 0.142, P < 0.001), a negative relation with FIB (r = -0.082, P = 0.012), and no correlation with PT (r =0.064, P =0.050) in the all patients. As well as, the eGDR demonstrated a positive relation with APTT (r = 0.173, P < 0.001), a negative relation with FIB (r = -0.093, P = 0.03), and no relation with PT (r = 0.045, P = 0.300) in the male subgroups. Additionally, this correlation persisted following the adjustment of other factors in multilinear regression analysis. However, the female subgroup demonstrated no correlation among eGDR and PT, APTT or FIB (r = 0.086, P = 0.083, r = 0.097, P = 0.05;r = -0.058, P = 0.240, respectively). Conclusion: Our study is the first to prove that eGDR demonstrates a correlation with coagulation indexes in T2DM patients. And, this correlation is gender-specific.

Single-cell transcriptome reveals effects of semaglutide on non-cardiomyocytes of obese mice.

Non-cardiomyocytes (nonCMs) play an important part in cardiac fibrosis pathophysiology, but the underlying molecular pathways are unknown. Semaglutide has cardioprotective properties, but it is still unclear whether it helps with cardiac fibrosis and what the processes are. The goal of this study is to use single cell transcriptomics approaches to investigate the molecular mechanism of semaglutide's cardioprotective action in obese mice. We found 15 non-CMs, with fibroblasts making up the majority of them. We found eight DEGs that altered significantly following semaglutide treatment by screening for differentially expressed genes (DEGs). DEGs were shown to have biological activities primarily related to extracellular matrix and collagen synthesis and distribution, with Serpinh1 and Pcolce expression being the most dramatically altered. Serpinh1 and Pcolce were mostly found in fibroblasts, which play a key role in the fibrosis of the heart. Furthermore, we discovered that semaglutide lowered cardiac collagen content and alleviated obesity-induced ventricular wall hypertrophy. As a result, our findings show that Serpinh1 and Pcolce, which are expressed by fibroblasts, may play a role in the development of obese cardiac fibrosis. By reducing Serpinh1 and Pcolce expression and delaying cardiac fibrosis, semaglutide may have a cardioprotective effect.

A metabonomics-based renoprotective mechanism analysis of empagliflozin in obese mice.

With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease.

UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury.

Background: This study is aimed at exploring the key genes and the possible mechanism of heart damage caused by obesity. Methods: We analyzed the GSE98226 dataset. Firstly, differentially expressed genes (DEGs) were identified in heart tissues of obese and normal mice. Then, we analyzed DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Thirdly, we constructed a protein-protein interaction (PPI) network and key modules and searched hub genes. Finally, we observed the pathological changes associated with obesity through histopathology. Results: A total of 763 DEGs were discovered, including 629 upregulated and 134 downregulated genes. GO enrichment analysis showed that these DEGs were mainly related to the regulation of transcription, DNA-templated, nucleic acid binding, and metal ion binding. KEGG pathway analysis revealed that the DEGs were enriched in long-term depression, gap junction, and sphingolipid signaling pathways. Finally, we identified UTP14A, DKC1, DDX10, PinX1, and ESF1 as the hub genes. Histopathologic analysis showed that obesity increased the number of collagen fibers and decreased the number of microvessels and proliferation of the endothelium and increased endothelial cell damage which further leads to dysfunction of cardiac microcirculation. Conclusion: UTP14A, DKC1, DDX10, PinX1, and ESF1 have been identified as hub genes in obesity-induced pathological changes in the heart and may be involved in obesity-induced cardiac injury by affecting cardiac microcirculatory function.

Single-cell transcriptomics identifies Col1a1 and Col1a2 as hub genes in obesity-induced cardiac fibrosis.

Obesity is a risk factor for cardiovascular disease, leading to ventricular dysfunction and cardiac fibrosis, in which non-cardiomyocytes (nonCMs) play an important role. Early detection and treatment of heart illness may help to limit its progression. We screened for key markers of obesity-induced cardiac fibrosis using single-cell transcriptomics techniques. To begin, an obese mouse model was constructed using a high-fat diet. From a pathogenic perspective, pathological alterations in the obesity-induced heart were found. Differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. Then, to look for hub genes, key modules of DEGs were built. Finally, the cellular location of the hub genes was investigated. In mice, a high-fat diet raised body weight, messed up myocardial shape, and increased cardiac collagen content. NonCMs transcriptome data revealed 15 different cell types, including fibroblasts, immunological cells, and endothelial cells. There were a total of 33 DEGs found, with 22 up-regulated genes and 11 down-regulated genes. DEGs have a high connection with collagen and extracellular matrix (ECM), according to functional enrichment analysis. Col1a1 and Col1a2 scored well in module analysis and hub gene screening, and were chosen as hub genes. Col1a1 and Col1a2 were shown to be mostly expressed by fibroblasts after localization study. As a result, we believe Col1a1 and Col1a2 may be important markers of obesity-induced cardiac fibrosis, in which fibroblasts play a critical role.