Decrease In Total Cholesterol Research Articles

Anti-hyperlipidemic effects of 500 mg spilanthol (SA3X) supplementation in people with dyslipidemia- a randomized, parallel-group placebo-controlled trial.

Dyslipidemia is a critical risk factor for cardiovascular disease. This study investigated the impact of 500 mg of spilanthol (SA3X) supplementation on lipid profiles in men with dyslipidemia using a randomized, parallel-group, placebo-controlled design. A total of 279 male participants were randomly allocated to one of four groups: SA3X without exercise, placebo without exercise, SA3X with exercise, and placebo with exercise. After a one-month control period, participants received SA3X capsules or placebo for three months. The exercise groups undertook standardized weight-lifting exercises four times weekly. Lipid profiles, biochemical parameters, and anthropometric measurements were monitored throughout and after the intervention. Both SA3X groups exhibited significant reductions in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) compared to the placebo groups. By day 90, the SA3X-no-exercise group showed a 16.78 % decrease in TC, while the SA3X-plus-exercise group demonstrated a 52.87 % decrease compared to placebo. Significant reductions in TG and LDL-C were noted at days 60 and 90 (p=0.01 and p=0.03, respectively). The SA3X-plus-exercise group also exhibited decreased random blood sugar levels at days 60 and 90 compared to placebo-plus-exercise. Moreover, decreases in C-reactive protein, creatine kinase, and serum creatinine levels were observed. SA3X supplementation, particularly when combined with exercise, effectively improved lipid profiles and various health markers in men with dyslipidemia. Adverse events, primarily taste disturbance, were mild. These findings suggest SA3X may be a promising adjunctive therapy for managing dyslipidemia, emphasizing its potential cardiovascular health benefits and supporting further investigation. CTRI/2021/05/033694; May 2021.

The Effect of Conjugated Linoleic Acid Supplementation on Lipid-Related Cardiovascular Biomarkers in Obese Adults

Background: Studies have shown incompatible findings regarding the effects of conjugated linoleic acid (CLA) supplementation on cardiovascular diseases (CVDs) risk factors. The aim of this study was to evaluate the effect of daily CLA supplementation on serum insulin and lipid- related CV biomarkers in obese adults. Methods: This randomized double-blind clinical trial was conducted on 54 adults categorized as class I obesity. The participants were randomly assigned into two groups (n=27) receiving a total of 3,000 mg/d of a 50:50 mixture of CLA isomers for three months in intervention group (IG) and 500 mg/d paraffin in placebo group (PG). Moreover, fasting serum levels of insulin, lipid profile, non-HDL-Cholesterol (non-HDL-C), atherogenic index of plasma (AIP), total triglyceride (TG)/HDL-C, and cholesterol/HDL-C ratio were measured. The main statistical analysis method was independent t-test for changes. Results: Changes between the groups showed a significant decrease in total cholesterol (P=0.03), LDL-C (P=0.04), and non-HDL-C (P=0.03), and also a significant increase in AIP (P=0.04) in IG compared to the PG. A remarkable decrease was found in HDL-C and cholesterol/HDL-C ratio. In addition, a remarkable increase was observed in TG in this context. Serum insulin, VLDL-C, and LDL-C/HDL-C ratio showed no significant changes during the intervention period. The use of CLA supplementation could help reduce some adverse fractions of serum lipid profile, particularly TC, non-HDL-C and LDL-C. Conclusions: Regarding the augmenting effects of CLA intake on AIP as a strong predictive marker for CVDs, it is difficult to confirm the beneficial effects of CLA supplementation in preventing CVDs.

Eicosapentaenoic acid supplementation alleviates pruritus, enhances skin moisture, and mitigates depression in maintenance hemodialysis patients

BackgroundThe objective of this study is to investigate the effects of oral supplementation with eicosapentaenoic acid (EPA) on circulating inflammatory factors, cardiometabolic parameters, skin moisturization, and the consequent symptoms of pruritus and depression in maintenance hemodialysis patients.Materials and methodsA total of 60 maintenance hemodialysis patients with severe pruritus symptoms completed this randomized, placebo-controlled study. Subjects of treatment group (n = 30) were instructed to consume 1000 mg fish oil (>900 mg EPA) and subjects of placebo group (n = 30) were instructed to consume 1000 mg soybean oil twice daily for 3 months. 5-D pruritus scoring, the Beck Depression Inventory (BDI) scale, skin moisture, serum creatinine, inflammatory factors, and cardiometabolic parameters were examined at baseline, and at the first, second, and third month post-supplementation.ResultsA significantly decreased pruritus level was observed in the treatment group, whereas an opposite result was observed in the placebo group. Increased skin moisture levels on both the face and arms were observed in the treatment group, but not in the placebo group. Supplementation of EPA significantly decreased serum CRP and IL-6 levels. Significant decreases in total cholesterol (CHO), and triglycerides (TG) levels were observed; however, a decrease in high-density lipoprotein (HDL) level was observed in the treatment group. There was no change in plasma creatinine (CR) observed in both groups. A significantly decreased BDI score was observed, whereas the opposite result was observed in the placebo group. A correlational study showed that the severity of pruritus was significantly associated with skin moisture and serum CRP. The severity of pruritus was also positively correlated with the BDI score.ConclusionSupplementation of EPA may provide multiple benefits including alleviating pruritus symptoms, addressing skin dryness, and mitigating depression in maintenance hemodialysis patients.

Changes in the exposure to cardiovascular disease risk factors in an 18 year follow-up study of a cohort of middle age urban residents. The Polish arm of the HAPIEE study.

Cross-sectional studies revealed that risk factor exposure increases with age but after reaching its peak decreases. This decline may be attributed to higher mortality among exposed individuals, lifestyle, or natural physiological changes related to age. Only prospective observations at the individual level provide credible insights of exposure during the transition from middle to old age. This study addresses changes in cardiovascular risk factors among older urban residents in Poland over an 18-year period. The study analyzed data from the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) project, a prospective cohort study investigating cardiovascular disease determinants. The sample included 312 participants (46-69 years). Data on demographic characteristics, blood lipids, blood pressure, body mass index (BMI), fasting glucose, and smoking status were collected at baseline and during re-examination. The analysis yielded a decrease in diastolic blood pressure, total cholesterol, LDL-cholesterol, and non-HDL cholesterol concentrations. However, BMI and fasting glucose levels increased. The decrease in blood pressure was mainly attributed to treatment effects, while the reduction in lipid concentrations was observed regardless of treatment. In addition, smoking prevalence decreased over the course of 18 years. The results of the prospective nearly 20 year observation at the individual level confirm findings from repeated cross-sectional studies on decrease in lipid concentrations, blood pressure and prevalence of smoking in older individuals.

Very Low Calorie Ketogenic Diet: What Effects on Lipid Metabolism?

This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia. The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.

The State of Lipid Metabolism in Old Rats in High Altitude Conditions Against the Background of the Use of Coenzyme Q10

The problem of population aging is relevant both in Kyrgyzstan and in the global space. At the same time, the preservation of the functional capabilities of the body of elderly people living in adverse climatic conditions is of particular importance. 20-30% of the inhabitants live in the mountainous area of Kyrgyzstan at an altitude of 2000-4000 meters above sea level. It is known that in high-altitude conditions, the body is influenced by extreme factors of the highlands, which accelerate the aging process and reduce life expectancy. This article presents data from experimental studies of energy metabolism disorders in old rats and its correction of coenzyme Q10 at an altitude of 3200 m above sea level. It was found that in old rats, under conditions of short-term adaptation in the mountains, an increase in the level of total cholesterol, triglycerides and low-density lipoproteins was shown, and the level of high-density lipoproteins decreased, indicating a violation of lipid metabolism. Also, due to oxidative stress in high-altitude conditions, the level of malondialdehyde, superoxide dismutase and catalase in the blood of animals was increased. Oral administration of coenzyme Q10 at a dose of 30 mg/kg of body weight 1 time per day for 30 days to old rats led to a decrease in total cholesterol, low-density lipoproteins, triglycerides and an increase in high-density lipoproteins, due to the fact that coenzyme Q10 protects the plasma membrane of the cell from lipid peroxidation, preventing oxidative modifications lipids, which leads to a reduced risk of coronary heart disease, heart attack and stroke.

Dietary silymarin improves performance by altering hepatic lipid metabolism and cecal microbiota function and its metabolites in late laying hens

BackgroundLiver lipid dysregulation is one of the major factors in the decline of production performance in late-stage laying hens. Silymarin (SIL), a natural flavonolignan extracted from milk thistle, is known for its hepatoprotective and lipid-lowering properties in humans. This study evaluates whether SIL can provide similar benefits to late-stage laying hens. A total of 480 68-week-old Lohmann Pink laying hens were randomly assigned into 5 groups, each group consisting of 6 replicates with 16 hens each. The birds received a basal diet either without silymarin (control) or supplemented with silymarin at concentrations of 250, 500, 750, or 1,000 mg/kg (SIL250, SIL500, SIL750, SIL1000) over a 12-week period.ResultsThe CON group exhibited a significant decline in laying rates from weeks 9 to 12 compared to the initial 4 weeks (P = 0.042), while SIL supplementation maintained consistent laying rates throughout the study (P > 0.05). Notably, the SIL500 and SIL750 groups showed higher average egg weight than the CON group during weeks 5 to 8 (P = 0.049). The SIL750 group had a significantly higher average daily feed intake across the study period (P < 0.05), and the SIL500 group saw a marked decrease in the feed-to-egg ratio from weeks 5 to 8 (P = 0.003). Furthermore, the SIL500 group demonstrated significant reductions in serum ALT and AST levels (P < 0.05) and a significant decrease in serum triglycerides and total cholesterol at week 12 with increasing doses of SIL (P < 0.05). SIL also positively influenced liver enzyme expression (FASN, ACC, Apo-VLDL II, FXR, and CYP7A1; P < 0.05) and altered the cecal microbiota composition, enhancing species linked to secondary bile acid synthesis. Targeted metabolomics identified 9 metabolites predominantly involved in thiamin metabolism that were significantly different in the SIL groups (P < 0.05).ConclusionsOur study demonstrated that dietary SIL supplementation could ameliorate egg production rate in late stage laying hens, mechanistically, this effect was via improving hepatic lipid metabolism and cecal microbiota function to achieve. Revealed the potentially of SIL as a feed supplementation to regulate hepatic lipid metabolism dysregulation. Overall, dietary 500 mg/kg SIL had the best effects.Graphical

Anti-Obesity Activity of Sanghuangporus vaninii by Inhibiting Inflammation in Mice Fed a High-Fat Diet.

Obesity is an unhealthy condition associated with various diseases characterized by excess fat accumulation. However, in China, the prevalence of obesity is 14.1%, and it remains challenging to achieve weight loss or resolve this issue through clinical interventions. Sanghuangpours vaninii (SPV) is a nutritional fungus with multiple pharmacological activities and serves as an ideal dietary intervention for combating obesity. In this study, a long-term high-fat diet (HFD) was administered to induce obesity in mice. Different doses of SPV and the positive drug simvastatin (SV) were administered to mice to explore their potential anti-obesity effects. SPV regulated weight, serum lipids, and adipocyte size while inhibiting inflammation and hepatic steatosis. Compared with the vehicle-treated HFD-fed mice, the lowest decreases in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were 9.72%, 9.29%, and 12.29%, respectively, and the lowest increase in high-density lipoprotein cholesterol (HDL-C) was 5.88% after treatment with different doses of SPV. With SPV treatment, the analysis of gut microbiota and serum lipids revealed a significant association between lipids and inflammation-related factors, specifically sphingomyelin. Moreover, Western blotting results showed that SPV regulated the toll-like receptor (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in HFD-diet mice, which is related to inflammation and lipid metabolism. This research presents empirical proof of the impact of SPV therapy on obesity conditions.

Anti-Obesity Activity of Sanghuangporus vaninii by Inhibiting Inflammation in Mice Fed a High-Fat Diet

Obesity is an unhealthy condition associated with various diseases characterized by excess fat accumulation. However, in China, the prevalence of obesity is 14.1%, and it remains challenging to achieve weight loss or resolve this issue through clinical interventions. Sanghuangpours vaninii (SPV) is a nutritional fungus with multiple pharmacological activities and serves as an ideal dietary intervention for combating obesity. In this study, a long-term high-fat diet (HFD) was administered to induce obesity in mice. Different doses of SPV and the positive drug simvastatin (SV) were administered to mice to explore their potential anti-obesity effects. SPV regulated weight, serum lipids, and adipocyte size while inhibiting inflammation and hepatic steatosis. Compared with the vehicle-treated HFD-fed mice, the lowest decreases in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were 9.72%, 9.29%, and 12.29%, respectively, and the lowest increase in high-density lipoprotein cholesterol (HDL-C) was 5.88% after treatment with different doses of SPV. With SPV treatment, the analysis of gut microbiota and serum lipids revealed a significant association between lipids and inflammation-related factors, specifically sphingomyelin. Moreover, Western blotting results showed that SPV regulated the toll-like receptor (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in HFD-diet mice, which is related to inflammation and lipid metabolism. This research presents empirical proof of the impact of SPV therapy on obesity conditions.

P-331 Unlocking metformin’s potential: exploring its impact on inflammation and oxidative pathways in an endometriosis mouse model

Abstract Study question Could endometriosis-associated pro-oxidative and pro-inflammatory condition be mitigated by metformin? Summary answer Metformin treatment tends to reduce fibrosis in ectopic tissues, while up-regulating anti-oxidative response enzymes. What is known already Endometriosis is a pro-inflammatory and pro-oxidative disease, which causes pain and infertility. Hormonal treatments used to control the disease must be stopped when a woman attempts to conceive, meaning new therapies are necessary. We had shown that endometriosis reduces fertility in a mouse model, which metformin treatment led to its reversal. Metformin, in addition to reducing blood glucose, reduces inflammation and systemic oxidation. It has also been shown to mitigate the growth of endometrial implants in the animal model. The objective of this work is to evaluate the intervention of metformin in the inflammatory and oxidative response pathways associated with endometriosis. Study design, size, duration Female mice were randomly divided into groups: 1-Endometriosis (n = 24); 2-Sham (n = 12); 3-Endometriosis with metformin (n = 21); 4-Sham with metformin (n = 16). Endometriosis was surgically induced by heterologous transplantation of endometrium from a donor into recipients of the same strain. Metformin (0,5mg/mL) was administered orally for 3 months. Half of the mice in each group were mated for the fertility study. Tissues analysed are described with “Eu” for eutopic and “Ec” for ectopic tissues, respectively. Participants/materials, setting, methods The implants were confirmed and monitored by ultrasound and serum glucose, estradiol and lipoprotein values were quantified by enzymatic-colorimetric methods. Fibrosis in eutopic and ectopic tissues was quantified after computer-assisted analysis in Masson’s Trichrome images. Dual-labelling immunofluorescence was performed for the proteins F4/80 and Galectin-3 (gal-3) and Western Blot (WB) was performed to quantify their expression and also NFkB, HO-1 and GPX-1, both in eutopic and ectopic tissues. Main results and the role of chance No differences were found in serum analysis between groups, apart from a decrease in total cholesterol and an increase in estradiol in pregnant compared to non-mated mice. Masson’s Trichrome stained sections revealed increased stromal fibrosis in both eutopic and ectopic tissues of non-mated Endometriosis groups compared to Sham groups(EuEnd vs. EuSham p = 0.018; EcEnd vs. EuSham p = 0.022; EuEnd vs. EuShamMet p = 0.0008; EcEnd vs EuShamMet p = 0,001). Metformin treatment showed a decreasing trend in fibrosis both in non-mated and pregnant, particularly in ectopic tissue, although statistical significance was not reached. Both eutopic and ectopic endometrium presented positive cells for f4/80 and gal-3, with some co-localization, in all groups. Metformin treatment led to the increase of the inflammation markers in the tissues of mice with ENDO: F4/80 was increased in eutopic tissue(p = 0.0002), while gal-3 (p = 0.004) and NF-kB (p = 0.03) augmented in ectopic tissue of non-mated. Pregnancy condition, on the other hand had a tendency for the decrease of these proteins. Metformin increased the expression of antioxidant defense enzymes HO-1 (p = 0,005) and GPX-1 (p = 0,0001) in the ectopic endometrium of non-mated mice. Metformin has shown to act in the up-regulation of anti-oxidative defenses that intervene in the control of endometriosis progression, but this effect was not evident during pregnancy. Limitations, reasons for caution Caution is necessary when extrapolating animal model data to humans due to species-specific differences in endometriosis patterns. Further studies, assessing pro-oxidative species, total antioxidant capacity, and potential anti-inflammatory roles of studied molecules, are essential to clarify the unexpected results in inflammatory pathways. Wider implications of the findings These findings highlight metformin, in a subtherapeutic dose, as a novel and safe approach to alleviate oxidative stress in endometriosis, offering a promising pharmacological solution for improving endometriosis-associated infertility, once we also had shown the reversal of infertility associated with endometriosis through metformin treatment. Trial registration number not applicable

Effect of Omega-3 Fatty Acids Supplementation in Pediatric Patients with Type 1 Diabetes Mellitus

Abstract Background Omega-3 fatty acids (O3FAs) are polyunsaturated fatty acids derived from fish oil. Beneficial effects of O3FA supplementation in a wide range of disease condition have been well studied. However; the role of O3FA in management of type 1 diabetes mellitus (T1DM) remains unclear and controversial. Objectives Therefore, we performed a randomized-controlled trial to assess the effect of oral O3FAssupplementation on glycemic control and lipid profile in pediatric patients with T1DM. Methods This study included 70 children and adolescents with T1DM. Patients were randomly assigned into two groups; intervention group and received oral O3FAs capsules (1 gram daily). The other group did not receive any supplementation and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c and fasting lipids. Results Supplementation with O3FAs was safe and well-tolerated. After 6 months, O3FAs adjuvant therapy for the intervention group resulted in a significant decrease of systolic blood pressure, insulin dose, FBG, HbA1c, triglycerides, total cholesterol and LDL-cholesterol compared with baseline levels and compared with the control group (p &amp;lt; 0.05). On the other hand, T1DM patients without O3FAs adjuvant therapy (control group) had higher blood glucose levels and HbA1c at study end compared with baseline levels (p &amp;lt; 0.001). Conclusions O3FAs as an adjuvant therapy to insulin improved blood glucose levels, glycemic control and dyslipidemia leading to reduction in insulin dose in pediatric patients with T1DM.

Efficacy and Safety of Resveratrol in Patients with Type 1 Diabetes Mellitus

Abstract Background Resveratrol is a food component found in grapes, peanuts, cranberries.. It has a wide range of effects including antimicrobial, anti-inflammatory and anti-apoptotic effects. Resveratrol could ameliorate diabetes in diabetic animals and it showed beneficial effects in adults with type 1 diabetes mellitus (T1DM). Objectives This randomized-controlled trial assessed the efficacy and safety of oral resveratrol supplementation on glycemic control and lipid profile in pediatric patients with T1DM. Methods This study included 60 children and adolescents with T1DM. Enrolled patients aged 12- 18 years with disease duration &amp;gt; 5 years. Patients were randomly assigned into two groups; intervention group who received oral resveratrol tablets 250 mg twice daily. The other group (did not receive any supplementation and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c% and fasting lipid profile. Results After 6 months, resveratrol therapy resulted in a significant decrease of FBG, HbA1c, triglycerides and total cholesterol compared with baseline levels and compared with the control group (p &amp;lt; 0.001). No significant difference was found between Patients with T1DM without resveratrol adjuvant therapy at baseline and at 6 months as regards any of the studied variables except for triglycerides and total cholesterol which were significantly increased at study end. Conclusions Resveratrol as an adjuvant therapy to insulin improved blood glucose levels, glycemic control and dyslipidemia without adverse effects in pediatric patients with T1DM.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome

BackgroundSmith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. MethodsPeople with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. Results12 individuals, ages 11–39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was − 0.28 % [(95 % CI, −2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. ConclusionsIn this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

Mechanism of Yupingfeng Powder on hepatic insulin resistance in type 2 diabetes mellitus rats by regulating IRS/PI3K/Akt pathway

Based on the insulin receptor substrate(IRS)/phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) pathway, the intervention effect of Yupingfeng Powder on type 2 diabetes mellitus(T2DM) rats was studied, and the potential mechanism of improving T2DM hepatic insulin resistance was explored. A T2DM rat model was established by feeding with high-fat and high-sugar feed combined with intraperitoneal injection of streptozotocin. Successfully modeled rats were selected and divided into a model group, a positive control group(MET), and a Yupingfeng Powder group. At the same time, a blank group was set up, and corresponding drugs were given by gavage. The model group and blank group were given an equal amount of physiological saline by gavage. During the experiment, body mass and fasting blood glucose were regularly measured, and glucose tolerance and insulin tolerance were measured at the end of the experiment. After the experiment, the levels of blood glucose, insulin, blood lipids, and related liver function indicators were measured; changes in liver pathological damage were observed, levels of liver monoamine oxidase were detected, and qRT-PCR was used to detect mRNA expression levels of IRS/PI3K/Akt pathway related genes. Compared with the model group, the Yupingfeng Powder group had an increase in body weight, a decrease in fasting blood glucose, fasting insulin, and steady-state model evaluation index, a decrease in the area under the curve of glucose tolerance and insulin tolerance tests, a decrease in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol content, and an increase in high-density lipoprotein cholesterol content. Compared with the model group, the Yupingfeng Powder group showed a decrease in liver monoamine oxidase levels, a decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and an increase in total protein and albumin levels. Hematoxylin-eosin(HE) staining showed a reduction in pathological liver cell damage. Compared with the model group, the Yupingfeng Powder group showed a significant increase in the mRNA expression levels of IRS1, PI3K, and Akt in the liver of rats, as well as a significant decrease in the mRNA expression levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). This indicates that Yupingfeng Powder can regulate the IRS/PI3K/Akt signaling pathway and glucose and lipid metabolism disorders, increase insulin sensitivity, improve hepatic insulin resistance, and thus play a therapeutic role in T2DM.

Epigenetic age acceleration is associated with blood lipid levels in a multi-ancestry sample of older U.S. adults.

Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids. After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages.

Identifying novel mechanisms of per- and polyfluoroalkyl substance-induced hepatotoxicity using FRG humanized mice.

Per- and polyfluoroalkyl substances (PFAS) such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) and perfluoro-2-methyl-3-oxahexanoic acid (GenX), the new replacement PFAS, are major environmental contaminants. In rodents, these PFAS induce several adverse effects on the liver, including increased proliferation, hepatomegaly, steatosis, hypercholesterolemia, nonalcoholic fatty liver disease and liver cancers. Activation of peroxisome proliferator receptor alpha by PFAS is considered the primary mechanism of action in rodent hepatocyte-induced proliferation. However, the human relevance of this mechanism is uncertain. We investigated human-relevant mechanisms of PFAS-induced adverse hepatic effects using FRG liver-chimeric humanized mice with livers repopulated with functional human hepatocytes. Male FRG humanized mice were treated with 0.067mg/L of PFOA, 0.145mg/L of PFOS, or 1mg/L of GenX in drinking water for 28days. PFOS caused a significant decrease in total serum cholesterol and LDL/VLDL, whereas GenX caused a significant elevation in LDL/VLDL with no change in total cholesterol and HDL. All three PFAS induced significant hepatocyte proliferation. RNA-sequencing with alignment to the human genome showed a total of 240, 162, and 619 differentially expressed genes after PFOA, PFOS, and GenX exposure, respectively. Upstream regulator analysis revealed that all three PFAS induced activation of p53 and inhibition of androgen receptor and NR1D1, a transcriptional repressor important in circadian rhythm. Further biochemical studies confirmed NR1D1 inhibition and in silico modeling indicated potential interaction of all three PFAS with the DNA-binding domain of NR1D1. In conclusion, our studies using FRG humanized mice have revealed new human-relevant molecular mechanisms of PFAS including their previously unknown effect on circadian rhythm.

Investigation of acute, sub-chronic toxicity, effects of mangiferin and mangiferin solid dispersion (HPTR) on Triton WR1339-induced hyperlipidemia on Swiss albino mice

Mangiferin is a xanthonoid found in Mango leaves in abundance with many effects as a hypoglycemic, antioxidant, and anti-inflammatory agent, plant metabolite, and so on. However, nowadays, mango leaves are merely a waste product in Vietnam. To take advantage of this valuable medicinal resource, extraction conditions of mangiferin using classical and ultrasound methods were researched, and mangiferin was purified from Cat Chu mango leaves (Mangifera indica L., Anacardiaceae) collected in Dong Thap. Ultrasound-assisted extraction method was conducted with the following conditions and mangiferin was extracted at a percentage of 6.728% with a purity of 91.11%. Purified mangiferin was evaluated using molecular absorption spectroscopy UV-Vis, scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, simultaneous thermal analysis (STA: TGA/DSC), and dissolution measurement method. To optimize the solubility and permeability of mangiferin, the solid dispersion system (HPTR) was made by the combination of HPMC 6M:mangiferin at the ratio of 1:5. To investigate the acute, sub-chronic toxicity and hypolipidemia effect of HPTR as compared to purified mangiferin, we followed guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD, and used tyloxapol (Triton WR1339, 400 mg/kg, i.p.) to induce hyperlipidemia. Our results indicated that purified mangiferin and HPTR extract showed no acute toxicity and sub-chronic toxicity and has potential as an antihyperlipidemic agent. The HPTR brought about a significant decrease in total cholesterol, triglycerides and LDL-c when compared to mangiferin, however there was no significance between them.

Biological evaluation of nutritional traditional fruit Mangifera camptosperma against diabetes and hyperlipidemia

IntroductionThe objective of the study was to determine antidiabetic and antihyperlipidemic effects of Mangifera camptosperma leaves extract using streptozotocin-induced animal model. MethodsThe leaves of M. camptosperma extracted with hydroethanolic (50:50) solvent using soxhlet apparatus. Traditional Chinese medicine (TCM) is often given as an adjuvant to alleviate diabetic symptoms. The plant extracts were used to determine presence of phytochemicals present in them using different tests. Diabetes was induced on animals using streptozotocin (STZ) 50 mg/kg through intra-peritoneal route. Oral administration of M. camptosperma extract at doses of 200 mg/kg and 400 mg/kg was used to assess its antidiabetic and antihyperlipidemic effects. ResultsThe phytochemical analysis showing presence of carbohydrates, alkaloids, tannins, glycosides, and flavonoids. The diabetic control group had blood glucose levels of 102 mg/kg and 126 mg/kg, respectively, after receiving the test medication, but the diabetic rats treated with the extract showed a substantial decrease to 90.11 ± 5.71 (200 mg/kg) and 82.12 ± 3.99 (400 mg/kg). If compared to the diabetic control group, the administration of 400 mg/kg of M. camptosperma for 21 days resulted in a substantial decrease (p < 0.05) in serum total cholesterol (106.12 ± 5.94 mg/dL) and triglyceride (83.11 ± 4.04 mg/dL), as well as an increase in HDL cholesterol (36.15 ± 3.04 mg/dL). This study found that while administered to diabetic rats, M. camptosperma lowered blood glucose levels and improved lipid profiles. DiscussionIt can be concluded from the study that the plant extract may be useful in treating hyperlipidemic and type-2 diabetes as an alternative medicine.

Weight, anthropometric and metabolic changes after discontinuing antiretroviral therapy containing tenofovir alafenamide (TAF) in people with HIV.

Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). While weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. We included participants who received at least six months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: TDF-based ART, dolutegravir/lamivudine (DTG/3TC), or long-acting cabotegravir/rilpivirine (CAB/RPV). Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54 kg (95% CI -0.98 to -0.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (CI -2.72 to -0.97), and to a decrease in mean total cholesterol (-0.44 mmol/L) and triglycerides (-0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17 kg, CI -0.82 to 0.48) or long-acting CAB/RPV (-0.64 kg, CI -2.16 to 0.89) did not lead to reductions in weight. Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within one year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.

The maintenance of long-term weight loss after semaglutide withdrawal in obese women with PCOS treated with metformin: a 2-year observational study.

Withdrawal of semaglutide is frequently followed by weight regain due to compensatory biological changes that prevent the maintenance of long-term weight loss. There are some studies implying that metformin might attenuate weight regain. The weight trajectory after discontinuation of short-term semaglutide treatment in obese women with PCOS who continued metformin treatment has not yet been evaluated. We explored changes in body weight, cardiometabolic and endocrine parameters in obese women with PCOS who continued treatment with metformin 2 years after discontinuation of short-term intervention with semaglutide. 25 women with PCOS and obesity, aged 33.7 ± 5.3 years (mean ± SD), were treated with once-weekly subcutaneous semaglutide 1.0 mg as an adjunct to metformin 2000 mg/day and lifestyle intervention for 16 weeks. At week 16, semaglutide was discontinued. Treatment with metformin 2000 mg/day and promotion of lifestyle intervention were continued during the 2-year follow-up period. Weight change, cardiometabolic, and endocrine parameters were assessed 2 years after semaglutide discontinuation. During semaglutide treatment phase, weight decreased from 101 (90-106.8) kg to 92 (83.3-100.8) kg. Two years after semaglutide withdrawal, weight was 95 (77-104) kg. The net weight loss 2 years after discontinuation of semaglutide remained significant when compared to baseline (p=0.003). At the end of the study, 21 out of 25 subjects had lower body weight compared to baseline. Improvements in cardiometabolic parameters including decrease in total and LDL cholesterol, fasting glucose, and glucose after OGTT that had been seen during semaglutide-treatment phase reverted towards baseline two years after semaglutide cessation. Free testosterone levels significantly decreased during semaglutide treatment from 6.16 (4.07-9.71) to 4.12 (2.98-6.93) nmol/l, (p= 0.012) and did not significantly deteriorate after semaglutide discontinuation. Two years after semaglutide withdrawal, women with PCOS who continued with metformin regained about one-third of the semaglutide-induced weight loss. At the end of the follow up, 84% of women had a lower body weight than at baseline.