Reduced Body Weight Research Articles

Dietary vegetable Sarcochlamys pulcherrima Gaud. And its bioactive compound myricitrin promotes white adipose browning in obese models via AMPK/SIRT1/UCP1 upregulation

Obesity, a worldwide epidemic, is a metabolic disturbance marked by acute adipose inflammation in the body due to accumulation of surplus nutrients. The aim of the study is to inverse the pathological development of obesity through conversion of WAT to brown AT by employing the traditionally acclaimed fat reducing efficacy of Sarcochlamys pulcherrima Gaud. (SP), a leafy dietary vegetable, and its isolated bioactive compound Myricitrin (MR). The study was carried out using 3T3-L1 adipocytes and HF diet C57BL/6 mice treated with SPEF (SP enriched fraction) and MR. Accumulation of triglycerides, lipids and ROS were checked along with mitochondrial biogenesis. Immunoblotting for AMPK dependent mitochondrial biogenesis, browning markers, lipogenic and inflammatory proteins were checked aided by in silico analysis. Histopathological analysis of the adipose tissue was supported with immunoblotting techniques. Treatment with MR significantly reduced the triglyceride, lipid and ROS levels with elevated mitochondrial biogenesis. MR also upregulates AMPK/SIRT1 dependent browning markers: UCP1 and PRDM16 and reduces pro-inflammatory cytokines with reduced lipogenesis. Administration of SPEF 150 and 300 mg/kg b.w for 6 weeks on HF diet mice showed significant reduction in body weight, triglyceride and cholesterol levels. Histology of adipose tissue showed brown AT depots in the treated group. In silico analysis showed the activation of SIRT1 substrate with MR leading to changes in adipose tissue morphology. The overall WAT browning efficacy of S. pulcherrima and its isolated bioactive compound MR was demonstrated in the present study. Further scientific substantiations can be carried out for the development of nature-based anti-obesogenic drugs.

Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

BACKGROUND Diabetic nephropathy (DN) is a severe microvascular complication of diabetes characterized by inflammation, oxidative stress, and renal fibrosis. Asiaticoside (AC) exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties, suggesting potential therapeutic benefits for DN. This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant pathway. AIM To investigate the renoprotective effects of AC against DN and elucidate the role of the NRF2/HO-1 pathway. METHODS The effects of AC on high glucose (HG)-induced proliferation, inflammation, oxidative stress, and fibrosis were evaluated in rat glomerular mesangial cells (HBZY-1) in vitro . A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury, inflammation, oxidative stress, and fibrosis. The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model. RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats, including reduced body weight, and elevated blood glucose, serum creatinine, blood urea nitrogen, and 24-h urine protein. Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, reactive oxygen species, and malondialdehyde levels while increasing superoxide dismutase activity. Additionally, AC suppressed the expression of fibrogenic markers such as collagen I, collagen IV, and fibronectin. AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase (Quinone) 1 protein expression in renal tissues and HG-induced HBZY-1 cells. CONCLUSION AC improves DN by reducing inflammation, oxidative stress, and fibrosis through the activation of the NRF2/HO-1 signaling pathway. These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction

GDF15 and FGF21, stress-responsive cytokines primarily secreted from the liver, are promising therapeutic targets for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the interaction between GDF15 and FGF21 remains unclear. We examined the effects of hepatocyte-specific GDF15 or FGF21 overexpression in high-fat diet (HFD)-fed mice for 8 weeks. Hydrodynamic injection of GDF15 or FGF21 sustained high circulating levels of GDF15 or FGF21, respectively, resulting in marked reductions in body weight, epididymal fat mass, insulin resistance, and hepatic steatosis. In addition, GDF15 treatment led to early reduction in body weight despite no change in food intake, indicating the role of GDF15 other than appetite loss. GDF15 treatment increased liver-derived serum FGF21 levels, whereas FGF21 treatment did not affect GDF15 expression. GDF15 promoted eIF2α phosphorylation and XBP1 splicing, leading to FGF21 induction. In murine AML12 hepatocytes treated with free fatty acids (FFAs), GDF15 overexpression upregulated Fgf21 mRNA levels and promoted eIF2α phosphorylation and XBP1 splicing. Overall, continuous exposure to excess FFAs resulted in a gradual increase of β-oxidation-derived reactive oxygen species and endoplasmic reticulum stress, suggesting that GDF15 enhanced this pathway and induced FGF21 expression. GDF15- and FGF21-related crosstalk is an important pathway for the treatment of MASLD.

Real-World Clinical Effectiveness of Liraglutide for Weight Management in Türkiye: Insights from the LIRA-TR Study

Introduction: Obesity is a complicated chronic disease associated with a series of other conditions. A weight loss of 5–10% has been shown to reduce obesity-related complications and improve quality of life. The efficacy and safety of liraglutide for reducing body weight have been demonstrated in clinical trials. This study evaluated the weight loss efficacy and adverse effects of liraglutide in those with obesity in the Turkish population. Methods: This is a retrospective cohort study; the patients that were included had a body mass index (BMI) of 27 or greater with additional comorbidities or a BMI of 30 or greater, and the patients were prescribed liraglutide for obesity treatment from the tertiary private clinic between January 2022 and January 2024. Their metabolic and anthropometric parameters were recorded at the initial appointment, and their body weight and adverse effects were followed up on during therapy. Results: For the 568 patients, of whom 487 (85.6%) were female, the mean values for age, weight, and BMI were 42.37 ± 10.50, 98.09 ± 17.48 kg, and 35.77 ± 5.45 kg/m2, respectively. Reductions in body weight at the 4th, 8th, 12th, and 24th weeks were 6.45 ± 2.32 kg, 10.66 ± 3.41 kg, 15.38 ± 8.30 kg, and 19 ± 9.06 kg, respectively; reductions in BMI at the 4th, 8th, 12th, and 24th weeks were 2.36 ± 1.00, 3.88 ± 1.25, 5.36 ± 1.76, and 7.09 ± 2.93, respectively; and the percentages of overall body weight loss at the 4th, 8th, 12th, and 24th weeks were 6.62 ± 2.1%, 10.75 ± 2.71%, 14.97 ± 6.8%, and 18.55 ± 4.63%, respectively (all p values < 0.0001). The percentage of patients who lost more than 5% and more than 10% of their initial weight was 100% at the 24th week. The most common side effect was nausea; no pancreatitis was observed. Conclusions: The results of our study indicate that liraglutide is an efficacious and safe treatment option for obesity in the Turkish population, in accordance with the findings from previous research.

Arabinoxylan Alleviates Obesity by Regulating Gut Microbiota and Bile Acid Metabolism.

Overweight and obesity are major and increasingly global public health concern. High intake of dietary fiber is negatively correlated with obesity and obesity-related metabolic diseases. Here, we investigated the impact of arabinoxylan on obesity based on the modification of gut microecology. Arabionxylan reduced body weight and improved glucose metabolism, as well as intestinal barrier function and metabolic endotoxemia in obese mice. Supplementation with arabinoxylan increased the relative abundance of Prevotellaceae_UCG_001, Lachnospiraceae_NK4A136_group, Clostridia_UCG_014, Alistipes, Bacteroides, and Ruminococcus, which was associated with the upregulated 7α-dehydroxylation function and production of secondary bile acids (deoxycholic acid and lithocholic acid). The modification of gut microbiota by arabinoxylan also influenced the production of SCFAs, genistein, daidzein, indolelactic acid, and indoleacetic acid, contributing to the amelioration of obesity. Our study highlights the antiobesity effects of arabinoxylan through the modification of gut microbiota and the production of bioactive metabolites.

Bacterial and clinical metabolic signatures and their interactions in obese patients post-bariatric surgery

BackgroundObesity is a growing health concern in China, closely linked to metabolic disorders such as type 2 diabetes. Laparoscopic Sleeve Gastrectomy (LSG) is effective in promoting weight loss and improving metabolic outcomes. Emerging evidence highlights the role of gut microbiota in metabolic regulation, yet the specific alterations in gut microbiota and their association with metabolic changes post-surgery in Chinese patients remain unclear. Understanding these shifts could provide key insights into optimizing treatment strategies for metabolic improvement following bariatric surgery.MethodsStool samples and clinical data were collected from 30 obese patients before and 6 months after surgery. The composition of the gut microbiota was analyzed through 16S rRNA sequencing, and Spearman correlation analysis was used to determine the association between gut microbiota and clinical indicators.ResultsThe analysis of 30 patients showed a significant decrease in Body Mass Index (BMI) (36.75 ± 4.09 kg/m2 vs 26.37 ± 3.47 kg/m2, p < 0.0001). Glucose metabolism, including Hemoglobin A1C levels, improved significantly (6.05 ± 0.96 vs 5.05 ± 0.25, p < 0.0001), and liver function as well as serum lipid levels were also notably improved. LSG increased the richness and composition of gut microbiota in obese patients post-surgery. These changes in gut microbiota were closely associated with improved clinical metabolic parameters.ConclusionLSG not only significantly reduces body weight while also alleviating metabolic syndrome and comorbidities by altering gut microbiota.

Effects of Specially Designed Energy-Restricted Diet on Anthropometric Parameters and Cardiometabolic Risk in Overweight and Obese Adults: Pilot Study.

This study examined the effects of a specially designed energy-restricted diet with alternate carbohydrate intake on body composition and cardiometabolic risk factors in overweight and obese adults. The aim was to assess whether the intervention could lead to significant weight loss, improve body composition, and reduce cardiometabolic risks. Sixty-five participants (34 women, 31 men) with an average BMI of 31.8 ± 9.1 kg/m2 (women) and 34.1 ± 6.4 kg/m2 (men) participated in a 14-week intervention. The diet included different days of carbohydrate intake and a 20% reduction in total daily energy consumption. Anthropometric measurements and biochemical parameters, including predictive indices of cardiometabolic risk, were determined at baseline and after the intervention. The intervention resulted in a significant reduction in body weight (mean weight loss of 17%, p < 0.001), with 64.6% of participants achieving a weight loss of at least 10%. Muscle mass as a percentage of total body weight increased. Cardiometabolic improvements were observed in fasting blood glucose (from 5.4 to 4.9 mmol/L, p < 0.001) and LDL cholesterol (from 3.38 to 2.81 mmol/L, p < 0.001). Gender-specific differences were found, particularly in HDL-C, which decreased significantly in women (p = 0.013), while there was a non-significant increase in men. Cardiometabolic indices, including the Visceral Adiposity Index (VAI) and the Cardiometabolic Index (CMI), also improved significantly. The alternate carbohydrate diet improved body composition, cardiometabolic health, and treatment adherence through metabolic flexibility. However, the short duration of this study and the lack of a control group suggest that further research is needed to assess long-term sustainability.

Effect of the consumption of probiotic foods in overweight/obese individuals: A systematic review and meta-analysis

This study aimed to assess whether the consumption of probiotic foods reduces anthropometric measurements in overweight and obese individuals through a systematic review and meta-analysis of randomized controlled trials. Of the 4370 identified studies, eight were eligible and included in the meta-analysis, which showed that there was a significant reduction in the variables body mass index, visceral fat area, subcutaneous fat area, body fat mass, fat percentage, waist circumference, hip circumference, and waist-to-hip ratio in the probiotic food consumption group compared to the control group. There was no significant reduction in body weight and lean mass. When evaluating meta-analyses of subgroups of microorganisms, positive outcomes in Lactobacillus gasseri (Lg2 and Lg3) are observed. Regarding the intervention period, the longer the duration of the intervention with probiotic foods, the better the outcome. In subgroup analyses, promising results were observed with the probiotic microorganism strain Lactobacillus gasseri SBT2055.

Lipid-lowering and antioxidant properties of probiotic Bifidobacterium animalis MSMC83 in rats on a high-fat diet.

Hyperlipidaemia, the abnormally high concentration of lipids such as cholesterol in the body, has a series of deleterious effects on health that are least in part are due to increased inflammation and oxidative stress. Probiotics are living microorganisms that possess the efficacy to improve health. Among the many effects that have been ascribed to probiotics is the potential to lower the body lipid content. Here, we used a rat model of induced hyperlipidaemia to assess the lipid-lowering and antioxidant properties of the probiotic strain Bifidobacterium animalis MSMC83 as well as its impact on intestinal barrier immunity and the intestinal microbiota. Oral probiotic intake led to a reduction of body weight, fasting blood glucose, and lipid levels, and increased expression of cholesterol-7α-hydroxylase and antioxidant enzymes. Additionally, B. animalis MSMC83 decreased the levels of liver enzymes and pro-inflammatory cytokines, leading to reduced hepatic steatosis. Furthermore, it re-established intestinal barrier integrity as shown by restoration of the tight junction protein zonula occludens-1 amount and reduced pathogen-induced inflammation in the intestinal epithelium as shown by readjusted expression of toll-like receptors (TLRs). Moreover B. animalis MSMC83 contributed to the maintenance of a balanced, diverse microbiome. Thus, our results indicate that B. animalis MSMC83 alleviates risk factors associated with hyperlipidaemia, suggesting its use as a probiotic to counter the effects associated with unhealthy diets.

Akkermansia muciniphila for the Prevention of Type 2 Diabetes and Obesity: A Meta-Analysis of Animal Studies

Background: More than half of the states in the U.S. report that over 30% of adults are obese. Obesity increases the risk of many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease, and can even reduce one’s lifespan. Similarly, the prevalence of type 2 diabetes follows a comparable trend. As a result, researchers are striving to find solutions to reduce obesity rates, with a particular focus on gut health, which has been previously linked to both obesity and type 2 diabetes. Recent studies suggest that Akkermansia muciniphila (Akk) may have a positive probiotic effect on preventing the onset of type 2 diabetes and obesity. Methods: We conducted a quantitative meta-analysis of 15 qualified animal studies investigating the effects of Akk administration as a probiotic. Results: The statistical analyses showed that Akk administration significantly reduced body weight gain by 10.4% and fasting blood glucose by 21.2%, while also significantly improving glucose tolerance by 22.1% and increasing blood insulin levels by 26.9%. However, our analysis revealed substantial heterogeneity between the control and experimental groups across all subgroups. Conclusions: Overall, Akk appears to be effective at reducing the onset of type 2 diabetes and diet-induced obesity. Long-term studies with larger sample sizes are needed to confirm these beneficial effects, as the current animal studies were of short duration (less than 20 weeks).

Toxicology profile of a novel GLP-1 receptor biased agonist-SAL0112 in nonhuman primates

Oral small-molecule GLP-1 receptor biased agonists exhibit promising treatment efficacy of type 2 diabetes and obesity. SAL0112 is a novel compound that has demonstrated remarkable efficacy in preclinical animal models. Herein, both in vitro and in vivo preclinical toxicity investigations were conducted to explore the safety profile of SAL0112. The HTRF assay and TR-FRET assay were utilized for cAMP detection. Patch clamp assay was employed for hERG potassium ion channel determination. Cynomolgus monkeys were used in a cardiovascular safety pharmacology study and a 13-week repeated dose toxicity study. The telemetry system was employed to detect cardiovascular indicators such as ECG, HR, and BP. During the repeated dose toxicity study, body weight, food intake, hematology, coagulation function test, serum biochemistry tests, and urine analysis were measured. Macroscopic and microscopic observations were conducted at the end of the study. TK studies were conducted on Day 1 and Day 91. SAL0112 exhibited a high degree of potency in activating the monkey GLP-1 receptor whereas had no effect on the rodent GLP-1 receptor. In contrast to Danuglipron, which demonstrated high potency on hERG with an IC50 value of 6.9 μM, the IC50 of SAL0112 on hERG was greater than 100 μM. Compared to the Vehicle Control group, no significant changes in cardiovascular indicators were observed in the cardiovascular safety pharmacology study after a single dose of SAL0112 up to 250 mg/kg (P > 0.05). A repeated dose toxicity study revealed moderate anorexigenic effects and a reduction in body weight, effects that were found to be reversible and not associated with any pathological changes. The NOAEL of SAL0112 is 150 mg/kg, providing an approximate safety margin of threefold. SAL0112 demonstrated a favorable safety profile in cynomolgus monkeys, with a substantial therapeutic window that supports the progression of this compound into clinical studies.

Stress-mediated Activation of Ferroptosis, Pyroptosis, and Apoptosis Following Mild Traumatic Brain Injury Exacerbates Neurological Dysfunctions.

Nearly half of mild traumatic brain injury (mTBI) patients continue to experience residual neurological dysfunction, which may be attributed to exposure to stress. Ferroptosis, a newly discovered form of cell death, is increasingly recognized for its involvement in the pathophysiology of TBI. Understanding the mechanisms by which stress influences mTBI, particularly through ferroptosis, is crucial for the effective treatment and prevention of mTBI patients who are sensitive to stressful events. In our study, a mouse mTBI model was established. An acute restraint stress (RS) and a chronic unpredictable mild stress (CUMS) model then were applied to make acute and chronic stress, respectively. We found acute RS significantly delayed the recovery of reduced body weight and short-term motor dysfunctions and exacerbated cell insults and blood-brain barrier leakage caused by mTBI. Further studies revealed that acute RS exacerbates neuronal ferroptosis, pyroptosis, and apoptosis by promoting iron overloading in the neocortex following mTBI. Interestingly, the inhibition of ferroptosis with iron chelators, including deferoxamine and ciclopirox, reversed pyroptosis and apoptosis. Moreover, CUMS aggravated neurological dysfunctions (motor function, cognitive function, and anxiety-like behavior) and exacerbated brain lesion volume. CUMS also exacerbates ferroptosis, pyroptosis, and apoptosis by intensifying iron deposition, along with decreasing the expression of neuronal brain-derived neurotrophic factor and glucocorticoid receptor in the neocortex post mTBI. These effects were also mitigated by iron chelators. Our findings suggest that alleviating ferroptosis induced by iron deposition may represent a promising therapeutic approach for mTBI patients who have experienced stressful events.

Types of Intermittent Fasting and Their Effects on Obesity and Type II Diabetes Mellitus

Obesity and type II diabetes mellitus affect millions of people both in Malaysia and worldwide due to sedentary lifestyles and unhealthy diets. Intermittent fasting reduces calorie intake by interweaving eating periods with prolonged fasting periods on a recurring basis. Therefore, it could be a potential solution to induce weight loss, leading to improved blood glucose level as observed in type II diabetes mellitus individuals. However, its feasibility remains unclear. This review aimed to compare the beneficial effects and adverse reactions from different types of intermittent fasting in obese and type II diabetes mellitus studies. The review was carried out by combing through several online databases. Keywords such as “Intermittent fasting”, “Obesity”, “Type II Diabetes Mellitus” were used and relevant articles were selected. The findings of this review showed that intermittent fasting is feasible and effective in reducing body weight and improving blood glucose. The beneficial effects of intermittent fasting appear to outweigh the adverse reactions. Having said that, intermittent fasting is unsuitable for individuals with packed schedules and certain health conditions such as pregnancy. This review will hopefully shed light on intermittent fasting as a potential intervention to combat obesity and type II diabetes mellitus. Further exploration of intermittent fasting could reduce both the morbidity and mortality rates from non-communicable diseases globally.

Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain.

Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain.We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity.LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex.The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10.In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions.

Establishing a Relationship between In Vitro Potency in Cell-Based Assays and Clinical Efficacious Concentrations for Approved GLP-1 Receptor Agonists.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) play an important role in the treatment of type 2 diabetes (T2D) and obesity. The relationship between efficacy and dosing regimen has been studied extensively for this class of molecules. However, a comprehensive analysis of the translation of in vitro data to in vivo efficacious exposure is still lacking. Methods: We collected clinical pharmacokinetics for five approved GLP-1RAs to enable the simulation of exposure profiles and compared published clinical efficacy endpoints (HbA1c and body weight) with in-house in vitro potency values generated in different cell-based assays. Additionally, we investigated the correlation with target coverage, expressed as a ratio between the steady state drug exposure and unbound potency, body weight, or HbA1c reduction in patients with T2D. Results: We found that the best correlation with in vivo efficacy was seen for in vitro potency data generated in cellular assays performed in the absence of any serum albumin or using ovalbumin. Residual variability was larger using in vitro potency data generated in endogenous cell lines or in the presence of human serum albumin. For the human receptor assay with no albumin, exposures above 100-fold in vitro EC50 resulted in >1.5% point HbA1c reduction, while a 5% BW reduction was related to approximately 3× higher exposures. A similar relationship was seen in the ovalbumin assay. Conclusions: Overall, the relationship established for in vitro potency and in vivo efficacy will help to increase confidence in human dose prediction and trial design for new GLP-1RAs in the discovery and early clinical phases.

Effectiveness of a fixed combination of empagliflozin with metformin in reduction of cardiovascular risk in patients with uncontrolled arterial hypertension and decompensated type 2 diabetes mellitus

Objective is to study the effectiveness of a fixed combination of empagliflozin and metformin in reducing cardiovascular risk in patients with uncontrolled arterial hypertension (AH) and decompensated type 2 diabetes mellitus (DM). Materials and methods. 36 patients with uncontrolled AH and decompensated type 2 diabetes mellitus aged 45 to 60 were examined. Before inclusion in the study, all patients received standard antihypertensive (angiotensin‑converting enzyme (ACE) inhibitor or angiotensin‑II receptor blocker (ARB) in combination with a calcium channel blocker and a thiazide‑like diuretic), glucose‑lowering (metformin) and hypolipidemic (atorvastatin) therapy. However, target levels of blood pressure (BP), glycated haemoglobin (HbA1c) and lipids were not achieved. After the initial examination, all patients were prescribed a fixed combination of empagliflozin and metformin at a dose of 12.5 mg/1000 mg 1—2 times a day, and antihypertensive and hypolipidemic therapy was continued. Re‑examination was carried out after 20 weeks. In the work, a statistical analysis of the obtained data was carried out using standard methods using Microsoft Excel 7.0 and SPSS 19.0 application packages. Results. The transfer of the examined patients from previous ineffective hypoglycemic therapy to a fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy made it possible to achieve the target levels of HbA1c in 69% of patients and target BP levels in 64%. The frequency of reaching target BP levels in the subgroup of patients who received ARB was significantly higher than in the subgroup of patients who received ACE inhibitors. The specified therapy contributed to a significant reduction in body weight, reaching the target levels of low‑density lipoprotein cholesterol (LDL‑C) and non‑high‑density lipoprotein cholesterol (Non‑HDL‑C) in more than a third of patients, and reducing the severity of albuminuria in some patients. The tested therapy, in general, led to reduction in cardiovascular risk and did not cause side effects that could lead to discontinuation of treatment. Conclusions. The fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy in patients with uncontrolled hypertension and decompensated type 2 diabetes mellitus contributed to the achievement in the vast majority of patients of the target levels of HbA1c in the blood and BP levels, reduced body weight, positive changes in lipid metabolism and kidney function, and demonstrated the possibility of a significant reduction in cardiovascular risk. A more pronounced decrease in BP was detected in the case of a fixed combination of empagliflozin and metformin with ARB compared to ACE inhibitors in this category of patients.

Effects of Vitamin C on Aluminum Chloride- Induced Neurotoxicity on the Hippocampal Cortex of Adult Wistar Male Rats

This study aimed to evaluate the neuroprotective effects of Vitamin C on aluminum chloride (AlCl₃)- induced brain damage, focusing on behavioral, biochemical, and histomorphological outcomes in a rodent model. Study Design: A total of 42 healthy male rats were randomly assigned to three groups: control, AlCl₃ -only, and AlCl₃ plus Vitamin C (500 mg/kg and 1000 mg/kg). The AlCl₃ groups received daily doses of AlCl₃, while the Vitamin C groups received concurrent Vitamin C supplementation. Methodology: Body weight, behavioral changes, biochemical markers of oxidative stress (MDA, SOD, GSH), and inflammation (TNF-α, IL-6) were assessed. Histomorphological analysis of the hippocampus was performed to evaluate structural damage. Behavioral assessments included locomotor and exploratory activity tests. Biochemical analyses measured oxidative stress and antioxidant enzyme activities. Results: AlCl₃ administration resulted in significant body weight loss, increased oxidative stress (elevated MDA, and SOD levels), and heightened inflammation (elevated TNF-α and IL-6). Behavioral tests showed increased excitatory activities, and increased anxiety levels as seen in increased rearing and grooming activities. Histomorphological examination revealed significant hippocampal damages as seen in the pale staining, shrunken pyramidal cells. Vitamin C co- administration mitigated these adverse effects, demonstrating reduced body weight loss, lower oxidative stress, decreased inflammation, and improved behavioral performance. Histological analysis indicated less hippocampal damage in the Vitamin C treated groups. Conclusion: As an antioxidant, Vitamin C effectively attenuates the neurotoxic effects of AlCl₃ by reducing oxidative stress and inflammation, and by protecting the hippocampal cellular integrity. These findings suggest that Vitamin C holds potential as a therapeutic agent for mitigating neurotoxicity induced by aluminum compounds.

Evaluation of Comparative Efficacy of Kutaki (Picrorhiza kurroa Royle ex. Benth) versus Atorvastatin in the Management of Dyslipidemia - A Randomised Controlled Trial

Introduction: Dyslipidemia is a lipoprotein metabolism condition marked by elevated blood levels of triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol as well as decreased levels of high-density lipoprotein (HDL) cholesterol. It can be correlated with (Medoroga) Medodushti Aim and objectives: To evaluate comparative effectiveness of Kutaki (Picrorhiza kurroa Royle ex. Benth) and Atorvastatin in the management of Dyslipidemia. Methodology: Total 160 patients were randomly divided into two equal groups. Patients in Study Group A were treated with Kutaki Vati and patients in Control Group B were treated with Atorvastatin for 60 days. Data was collected by assessment of Objective parameters like body weight, BMI, lipid levels (TCH-Total serum cholesterol , HDL-High-density lipoproteins, LDL-Low-density lipoproteins, TG- Serum Triglycerides, VLDL-Serum Very Low-density lipoproteins, AST, ALT, S.Urea, S.Creatinine, Fasting blood sugar on the day 0, 30 and 60. The analysis was done with the help of inferential and descriptive statistics. Observation and Result-Kutaki and Atorvastatin both showed significant improvement in lipid levels but Kutaki showed reduction in body weight and BMI with correction in deranged Agni and bowel habit( constipation) which was not seen in Atorvastatin group. Kutaki showed no rise in AST, ALT, S Creatinin and S.urea indicating its hepatoprotective and nephroprotective properties. Conclusion-Both groups are equally effective in the management of Dyslipidemia (Medoroga).But Kutaki is effective in reducing bodyweight and BMI and safe as it showed no rise in AST, ALT, S Creatinin and S.urea.

Changes in echocardiographic parameters after hemodialysis session in a North African pediatric population with end-stage renal disease and without known heart disease.

Children undergoing long-term hemodialysis (HD) face a reduction in life expectancy mostly due to cardiovascular mortality. Effects of HD on cardiac function have not been fully elucidated in pediatric population. This study aimed to assess HD session impact on cardiac function in pediatric patients using conventional and strain echocardiography. We performed a prospective, comparative study of echocardiographic parameters before and after single HD session in a chronic HD pediatric population. We enrolled between the 1st and 30th September 2023, all consecutive patients with end-stage renal disease (ESRD) aged up to 18 years old on maintenance HD three times weekly for at least three months. All patients underwent conventional and left ventricular (LV) longitudinal strain echocardiography in a window of 30-60 minutes before and after HD. 23 patients, 14.8 ± 2.1 years old and 47.8% male, were enrolled. Reductions in body weight and blood pressure were observed after HD, whereas heart rate increased. Significant decrease in LV and left atrial diameters and volumes after HD session were observed. Mitral peak E velocity, as well as average E/e' were significantly lower after HD. Although LV ejection fraction was unchanged, global longitudinal strain for LV was significantly reduced after dialysis (-17.3 ± 3.0% vs. -14.9 ± 2.4%, p=4.10-8). Patent deterioration in LV systolic function following HD was identified by speckle tracking echocardiography (STE). STE has the potential to unmask early myocardial dysfunction even when there is no evident alteration in conventional systolic function parameters in children with ESRD.

7492 Fibroblast Growth Factor 21 In The Diagnosis And Treatment Of Metabolic Disorders

Abstract Disclosure: H.M. Heshmati: None. H.S. Abu-Lebdeh: None. Background: Fibroblast growth factor 21 (FGF21), a member of the human FGF superfamily, is a 181 amino acid peptide hormone primarily produced by the liver. The gene of FGF21, located on chromosome 19, was cloned in 2000. FGF21 is involved in the maintenance of metabolic homeostasis. This review presents an update on the relevance of FGF21 in the diagnosis and treatment of metabolic disorders including obesity, nonalcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes. Methods: A systematic search of literature was conducted using the search terms fibroblast growth factor 21, obesity, nonalcoholic fatty liver disease, dyslipidemia, and type 2 diabetes. Results: FGF21 is a stress hormone with effects on energy expenditure and metabolism of lipids and glucose. FGF21 exerts its endocrine action in the central nervous system and adipose tissue. The serum FGF21 levels in normal subjects increase with aging. Stressful conditions (e.g., fasting status, protein restriction, exercise, metabolic disorders, kidney diseases, cardiovascular diseases, and sepsis) increase FGF21 secretion. Serum FGF21 levels are increased in obesity, NAFLD, dyslipidemia, and type 2 diabetes. Some of these patients may have a state of FGF21 resistance. The resistance to FGF21 is related, at least in part, to the presence of high circulating levels of fibroblast activation protein, a protease that inactivates FGF21. It has been suggested that the exercise-induced weight loss can be due to increased FGF21 secretion and decreased FGF21 resistance in adipose tissue. Serum FGF21 level has the potential to be used as a biomarker for early diagnosis of metabolic disorders (e.g., NAFLD and type 2 diabetes). Based on different metabolic properties of FGF21, FGF21-based therapy has been considered as an attractive approach for the treatment of metabolic disorders. Since native FGF21 has poor pharmacodynamic properties (e.g., short half-life and proteolytic cleavage by proteases), long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been synthesized and tested in clinical trials for the treatment of obesity, NAFLD, dyslipidemia, and type 2 diabetes. The available results show that FGF21 analogs can reduce body weight, liver fat, blood lipids, and fasting insulin/insulin resistance. Overall, the treatment with these analogs is safe and well tolerated. Conclusion: FGF21 is a predominantly liver-derived peptide hormone regulating energy expenditure and metabolism of lipids and glucose. Serum FGF21 levels are increased in several metabolic disorders including obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is an attractive target for the treatment of these metabolic disorders. Despite some promising results observed with the use of FGF21 analogs, more clinical studies are needed before recommending FGF21-based therapies in metabolic disorders. Presentation: 6/2/2024