Parameters Of Lipid Metabolism Research Articles

PF-05231023 reduces lipid deposition in apolipoprotein E-deficient mice by inhibiting the expression of lipid synthesis genes

Fibroblast growth factor 21 (FGF21) is a peptide hormone that is primarily expressed and secreted by the liver. The hormone is crucial for regulation of glucose homeostasis, lipid metabolism, and energy balance. Compared with natural FGF21, FGF21 analogs have become drug candidates for the treatment of cardiovascular and metabolic diseases owing to their long half-life and greater stability in vitro. Apolipoprotein E (Apoe)-knockout (Apoe−/−) mice exhibit progressive disruptions in lipid metabolism in vivo and develop further atherosclerosis pathological features owing to Apoe deletion. Therefore, this study used an Apoe−/− mouse model to investigate the effects of a long-acting FGF21 analog (PF-05231023) on lipid metabolism and related parameters. Eighteen Apoe−/− female mice were fed a Western diet equivalent for 12 weeks, and then randomly assigned to intraperitoneally receive either physiological saline (the control group) or 10 mg/kg PF-05231023 (the treatment group) three times a week for seven consecutive weeks. Body composition, glucose tolerance, blood and liver cholesterol, triglyceride levels, liver vacuolization levels, peri-ovarian white adipocyte hypertrophy, aortic atherosclerotic plaque formation, and the expression of genes related to lipid metabolism in adipose tissue were subsequently assessed before and after treatment. The aortic atherosclerotic plaque area was reduced in mice in the PF-05231023 treatment group compared with that in the saline group. Although the effect of PF-05231023 on the plasma biochemical indexes of mice was small, it significantly reduced lipid levels and lipid droplet accumulation in the liver, and reduced adipocyte hypertrophy in white adipose tissue. Transcriptome analysis of adipose tissue showed that PF-05231023 treatment downregulated the expression of lipid synthesis-related genes and inhibited the sterol regulatory element binding transcription factor 1 gene, thereby improving lipid deposition. PF-05231023 effectively improved the lipid metabolism of Apoe−/− mice, demonstrating an anti-atherosclerotic effect and providing a scientific basis and experimental foundation for the clinical treatment of cardiovascular diseases by using long-acting FGF21 analogs.

Probiotics Alleviate Microcystin-LR-Induced Developmental Toxicity in Zebrafish Larvae.

Microcystin-LR (MCLR) poses a significant threat to aquatic ecosystems and public health. This study investigated the protective effects of the probiotic Lactobacillus rhamnosus against MCLR-induced developmental toxicity in zebrafish larvae. Zebrafish larvae were exposed to various concentrations of MCLR (0, 0.9, 1.8, and 3.6 mg/L) with or without L. rhamnosus from 72 to 168 h post-fertilization (hpf). Probiotic supplementation significantly improved survival, hatching, and growth rates and reduced malformation rates in MCLR-exposed larvae. L. rhamnosus alleviated MCLR-induced oxidative stress by reducing reactive oxygen species (ROS) levels and enhancing glutathione (GSH) content and catalase (CAT) activity. Probiotics also mitigated MCLR-induced lipid metabolism disorders by regulating key metabolites (triglycerides, cholesterol, bile acids, and free fatty acids) and gene expression (ppara, pparb, srebp1, and nr1h4). Moreover, 16S rRNA sequencing revealed that L. rhamnosus modulated the gut microbiome structure and diversity in MCLR-exposed larvae, promoting beneficial genera like Shewanella and Enterobacter and inhibiting potential pathogens like Vibrio. Significant correlations were found between gut microbiota composition and host antioxidant and lipid metabolism parameters. These findings suggest that L. rhamnosus exerts protective effects against MCLR toxicity in zebrafish larvae by alleviating oxidative stress, regulating lipid metabolism, and modulating the gut microbiome, providing insights into probiotic-based strategies for mitigating MCLR toxicity in aquatic organisms.

Visceral fat mass dynamics in a 2-year randomized STrength versus ENdurance training trial in people with obesity.

To compare the effectiveness of strength versus endurance training on reducing visceral fat in individuals with obesity. For the STrength versus ENdurance (STEN) 24-month randomized clinical trial, we assigned 239 participants with abdominal obesity to either strength or endurance training (two to three times a week, 60 min/training session) in addition to standard nutritional counselling to promote a healthy diet. Changes in abdominal visceral adipose tissue (VAT) area quantified by magnetic resonance imaging after 12 months were defined as a primary endpoint. Participants (aged 44 years, 74% women, body mass index: 37 kg/m2, mean VAT volume: 4050 cm3) had an approximately 50% retention rate and a 30% good training programme adherence at 12 months. There was no difference between strength and endurance training in VAT volume dynamics after 12 and 24 months (p = .13). Only in the good adherence group did we find a trend for reduced VAT volume in both training regimens. Independently of the exercise programme, there was a continuous trend for moderate loss of abdominal subcutaneous AT volume, body fat mass, body mass index and improved parameters of insulin sensitivity. Although parameters of physical fitness improved upon both exercise interventions, the dynamics of resting energy expenditure, glucose and lipid metabolism parameters were not different between the intervention groups and did not significantly improve during the 2-year trial (p > .05). Despite heterogeneous individual training responses, strength and endurance training neither affected VAT volume nor key secondary endpoints differently.

Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population

BackgroundAtherosclerosis is an inflammatory disease. Interleukin 18 (IL-18) is an inflammatory molecule that has been linked to the development of atherosclerosis and cardiovascular disease. ObjectiveTo evaluate the possible relationship between plasma levels of IL-18 and the presence of atherosclerosis evaluated at the carotid level, as well as to analyze the possible modulation by different polymorphisms in a Mediterranean population. Material and methods746 individuals from the metropolitan area of ​​Valencia were included, recruited over a period of 2 years. Hydrocarbon and lipid metabolism parameters were determined using standard methodology and IL-18 using ELISA. In addition, carotid ultrasound was performed and the genotype of 4 SNPs related to the IL-18 signaling pathway was analyzed. ResultsPatients with higher plasma levels of IL-18 had other associated cardiovascular risk factors. Elevated IL-18 levels were significantly associated with higher carotid IMT and the presence of atheromatous plaques. The genotype with the A allele of the SNP rs2287037 was associated with a higher prevalence of carotid atheromatous plaque. On the contrary, the genotype with the C allele of the SNP rs2293224 was associated with a lower prevalence of atheromatous plaque. ConclusionsHigh levels of IL-18 were significantly associated with a higher carotid IMT and the presence of atheromatous plaques, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the IL-18 receptor gene and the presence of atheroma plaque.

Effect of Lacticaseibacillus casei LC2W Supplementation on Glucose Metabolism and Gut Microbiota in Subjects at High Risk of Metabolic Syndrome: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.

Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administrationto improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020.

IMPACT OF CORONARY ARTERY DISEASE ON STEATOTIC LIVER DISEASE PROGRESSION

Introduction. Metabolic dysfunction-associated steatotic liver disease and coronary artery disease often exacerbate each other, leading to a more severe course of both conditions. The aim of this study is to evaluate the role of coronary artery disease in dislipidemia and liver fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Forty-six patients with metabolic dysfunction-associated steatotic liver disease were examined. Patients were divided into two groups based on the presence of concomitant coronary artery disease: group I (n=24) included patients with both metabolic dysfunction-associated steatotic liver disease and coronary artery disease, while group II (n=22) included patients with metabolic dysfunction-associated steatotic liver disease only. A third group (Group III) comprised healthy individuals. Specific lipid metabolism parameters, obesity stage, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) activity, and platelet count were examined. Fibrosis stage was evaluated using the FIB-4 score. The findings obtained were statistically processed. Results. Arterial hypertension was more prevalent in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease. In group I, arterial hypertension was observed in 95.8% of cases, whereas in group II, it was observed in 40.9% of cases (χ2=16.35, p=0.00005). Patients with metabolic dysfunction-associated steatotic liver disease exhibited elevated levels of total cholesterol, low-density lipoproteins, and triglycerides, leading to an increased atherogenic index. Conversely, high-density lipoprotein levels were decreased (p>0.05). The degree of fibrosis according to the FIB-4 score was 1.45 times higher in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease compared to those without coronary artery disease.

A novel compounded cyproheptadine hydrochloride oral solution: Accelerated stability study and effects on glucose and lipid metabolism in Wistar rats

The present study developed a compounded oral solution (COS) containing an active component cyproheptadine hydrochloride (CY) in association with pharmaceutical adjuvants. The main objective is to demonstrate the stability of this solution and the in vivo effects on serum and liver parameters of glucose and lipid metabolism. After 180 days of analysis the COS showed physicochemical stability (pH and specific gravity) when submitted to different temperatures (24 °C and 40 °C), but the chemical stability, presented by the content of CY (%) in the formulation, showed that the degradation rate of CY increased 20x when submitted to a stress condition (40 °C). Male Wistar rats were treated with IOS 1.5 (industrial oral solution 1.5 mg.kg-1) or saline for 21 days and IOS 5.0 or COS (5 mg.kg-1) or placebo by gavage for 23 days. Treatment with IOS 1.5 increased liver cholesterol by 30 % without changing liver and body weight in this group. In contrast, treatment with IOS and COS (5 mg.kg-1) increased final body weight by 8 % compared to placebo. Interestingly, the COS group had increased liver glycogen accompanied by reduced food intake compared to IOS. However, COS and IOS 5.0 did not induce changes in adipose tissue weight, liver weight, as well as serum glucose, triacylglycerol and cholesterol levels. This work provides us with data that prove the stability of the compound solution at room temperature, as well as inducing an increase in the final body weight of rats with no alteration in glucose and lipid metabolism.

Evaluation of the Clinical Effectiveness of the Drug Laennec in Complex Rehabilitation of Patients with Post-COVID Syndrome: a Randomized Trial

INTRODUCTION. The development of post-COVID syndrome is accompanied by an increase in markers of systemic inflammation, a violation of the detoxification function of the liver, caused by both direct viral damage to hepatocytes and an increased iatrogenic load on the hepatobiliary system due to polypharmacy. AIM. Studying the use of the drug Laennec in the rehabilitation period as a hepatoprotector and immunomodulator in patients with post-COVID syndrome. MATERIALS AND METHODS. The study included 40 patients with post-COVID syndrome aged 30 to 60 years, with steatosis and steatohepatitis (increased levels of liver transaminases). The clinical effectiveness of Laennec was assessed based on the dynamics of pro-inflammatory biomarkers, liver metabolism indicators, as well as functional tests and psychological questionnaires. RESULTS. The inclusion of Laennec in the rehabilitation program for patients with post-COVID syndrome leads to a more pronounced improvement in lipid metabolism parameters, correction of liver metabolism parameters, a decrease in the level of pro-inflammatory biomarkers, and an improvement in the quality of life of patients than in the control group. DISCUSSION. Significantly significant positive dynamics in the severity of complaints of general weakness and sleep disturbance, as well as indicators of memory impairment and impaired concentration in the main group could indicate the achievement of anabolic, neurotrophic and bioenergetic effects of the Laennec drug. A significantly significant decrease in the level of liver transaminases in the main group indicates the hepatoprotective effect of the drug Laennec, due to the amino acids, vitamins and microelements included in the drug, which support the reactions of phases 1 and 2 of liver detoxification. Normalization of elevated pro-inflammatory markers (ferritin, IL-6, CRP) in patients of the main group may indicate the presence of anti-inflammatory and immunoregulatory effects of the Laennec drug. CONCLUSIONS. A course prescription of the drug Laennec for the purpose of correcting pro-inflammatory markers and hepatoprotection can be recommended for use in complex non-drug rehabilitation to increase its clinical effectiveness, as well as improve subjective indicators of the quality of life of patients with post-COVID syndrome.

Clinical and pathogenetic informativeness of laboratory parameters of inflammation and lipid metabolism in patients with chronic epitympano-antral purulent otitis media

Clinical and pathogenetic informativeness of laboratory parameters of inflammation and lipid metabolism in patients with chronic epitympano-antral purulent otitis media

Clinical markers of cognitive impairment in patients with chronic heart failure of ischemic origin during out-patient regular follow-up: a cross-sectional study

Background: Cognitive impairment (CI) is present in 25–50% of chronic heart failure (CHF) patients. Doctors who monitor patients with cardiovascular disorders do not have clearly set criteria for their referral to a neurologist in case of suspected CI. Therefore, CHF patients do not receive treatment for CI on time.
 Aim: To identify significant clinical markers of CI in patients with CHF of ischemic origin.
 Materials and methods: This cross-sectional cohort study included 134 patients with CHF of ischemic origin (mean age 63.36 ± 10.63 years; men, 76.12%), who were regularly monitored in a municipal polyclinic. All patients were tested for CI with the Montreal Cognitive Assessment Scale (MoCA); basic hemodynamic parameters, lipid profile, brain natriuretic peptide (NT-proBNP) were assessed, and triglyceride-glucose index (TyG) and body mass index (BMI) were calculated. Cardio-ankle vascular index (CAVI) was measured, echocardiography and a 6-minute walk test (SMWТ) were performed and past history of CHF, arterial hypertension (AH) and diabetes mellitus (DM) was collected.
 Results: CI (MoCA score ≤ 25) was detected in 85 (63.43%) outpatients with CHF of ischemic origin; the group without CI (MoCA score 26) included 49 (36.67%) patients. There were significant correlations between MoCA and CAVI scores (partial correlation coefficient, r = -0.802, p 0.001; adjusted squared multiple correlation coefficient (adj. R2) = 0.881, p 0.001), MoCA and TyG (r = -0.357, p = 0.029; adj. R2 = 0.363, p 0.001), MoCA and SMWТ (r = -0.211, p = 0.037; adj. R2 = 0.696, p 0.001). The multivariate test for significance of planned comparisons between CAVI and MoCA scores (Wilks' lambda) was 0.005 (F = 4.74; p 0.001).
 Conclusion: CAVI, TyG and SMWТ values are the clinical markers of CI in patients with CHF of ischemic origin. There is a direct association between increased CAVI and the presence of CI, regardless of age, lipid metabolism parameters, structural and functional heart parameters, CHF duration, AH and DM. Identification of these markers could be an indication for an in-depth assessment of CHF patients by a neurologist.

Influence of dapagliflozin on cardiovascular remodeling in hypertensive patients with accompanying type 2 diabetes

Aim. To compare the results of 12-week treatment of patients with stage II hypertension (HTN) with accompanying diabetes mellitus (DM) type 2 between the combination of metformin + dapagliflozin and metformin monotherapy by studying changes in the elastic properties of the common carotid arteries (CCA), echocardiographic indicators, 24-hour ambulatory blood pressure monitoring (ABPM) and laboratory parameters of lipid and carbohydrate metabolism. Materials and methods. 24 patients with stage II HTN with type 2 DM were involved in the study, the average age was 60.4 years, 50 % – men. Patients in the first group were randomized to receive metformin, and the second group – to receive a combination of metformin and dapagliflozin. At inclusion and after 3 months of treatment, basic anthropometric data, laboratory indicators of lipid and carbohydrate metabolism, ABPM, echocardiography, and indicators of CCA local stiffness were studied. Statistical analysis was performed, the probability of differences is at the level of p < 0.05. Results. In both observation groups, there was a comparable decrease in SCORE 2-Diabetes range, glucose and glycated hemoglobin, total cholesterol, LDL cholesterol, average daily systolic blood pressure (SBP), daily SBP load, day and night pulse BP, as well as an increase in speed systolic movement of the lateral fibrous ring of the mitral valve (S lat). Only in the metformin + dapagliflozin group a decrease in the adipose tissue level, the average daily diastolic blood pressure (DBP), the burden of DBP, the size of the left atrium and right ventricle, an increase in the movement speeds of the medial (e’med), lateral (e’lat) ring of the mitral and of the tricuspid (e’tk) valve in the period of early diastolic filling of the ventricles, velocities of systolic movement of the medial fibrous ring of the mitral (S med) and tricuspid (S tk) valves, a decrease in the ratio E/e’, and an improvement in the elastic properties of general carotid arteries were observed. Conclusions. In persons with HTN stage II with DM type 2 the addition of dapagliflozin to the treatment regimen was associated with better control of blood pressure, improvement of diastolic function and longitudinal contractility of the left ventricle, elastic properties of CCA.

Laboratory indicators of hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different subtypes of ischemic stroke

Objective: to evaluate laboratory parameters of hemostasis, lipid metabolism and endothelial dysfunction and their relationship in men aged 18–50 years with atherothrombotic (ATS), lacunar (LS) and cardioembolic (CES) stroke. Material and methods. The study included 89 men with ATS (n=36), LS (n=34) and CES (n=19). Neuroimaging, ultrasound and laboratory blood serum analyses were performed in all patients. Results. The mean age of the patients was 42.6±5.3 years. The main risk factors for ATS, LS and CES included: arterial hypertension (75; 97.8 and 73.7% of cases, respectively), dyslipidemia (60; 41.3 and 42.1%), tobacco smoking (71.7; 67.4 and 52.6%), regular alcohol consumption (35; 19.6 and 36.8%), obesity (23.3; 8.7 and 15.8 %), diabetes mellitus (8.3; 6.5 and 10.5 %). Lower tissue plasminogen activator levels were found in patients with CES (2.66±1.77 ng/ml) compared to patients with LS (3.38±3.0 ng/ml) and ATS (3.48±2.45 ng/ml). Plasminogen activator inhibitor-1 levels were significantly increased in all stroke subtypes. The mean level of soluble thrombomodulin was highest in patients with LS (100.86±58.22 pg/ml) compared to patients with ATS (96.37±85.71 pg/ml) and CES (75.28±39.36 pg/ml). The level of asymmetric dimethylarginine was higher in patients with ATS (1.46±0.42 μmol/l) and in patients with LS (0.79±0.37 μmol/l), and in patients with CES (0.4±0.13 μmol/l) it was within the reference values. Conclusion. We noted differences in laboratory parameters of the hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different stroke subtypes (ATS, LS and CES), as well as clinical and laboratory correlations.

A Cross-Sectional Pilot Study on Association of Ready-to-Eat and Processed Food Intakes with Metabolic Factors, Serum Trans Fat and Phospholipid Fatty Acid Compositions in Healthy Japanese Adults.

Frequently consuming processed and ready-to-eat (RTE) foods is regarded as unhealthy, but evidence on the relationships with circulating metabolic parameters is lacking. Japanese residents of a metropolitan area, 20 to 50 years of age, were studied in terms of anthropometric and biochemical parameters, including circulating trans fat and serum phospholipid fatty acid levels. Processed foods, except drinks and dairy items, were categorized according to requirements for additional ingredients and cooking before eating. Processed and RTE foods were divided according to fat and/or oil content into non-fatty or fatty foods. The participants were grouped into tertiles based on the energy percent (En%) derived from fatty-RTE foods. Fatty-RTE En% showed negative associations with fish, soybean and soybean products, dairy, eggs, vegetables, seaweed/mushrooms/konjac, fruit and non-oily seasonings reflecting lower dietary fiber, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and mineral and vitamin intakes, while the associations with fat/oil, confectionaries, and sweet beverages were positive. Fatty-RTE En% consumption was positively associated with alkaline phosphatase, leucine aminopeptidase, direct bilirubin, elaidic acid, and C18:2 but inversely associated with HDL cholesterol, C15:0, C17:0, EPA, and DHA. A higher fatty-RTE food intake was suggested to contribute to unbalanced nutrient intakes, as reflected in lipid metabolic parameters. Further large-scale studies are needed to evaluate the quality and impacts of RTE foods.

Oral supplementation of Njansan (Ricinodendron heudelotii Bail) and sardine fillets (Sardina pilchardus) oils alleviate high-fat diet-induced obesity in rats by regulating lipid metabolism and stress oxidative parameters

Background: Obesity has become one of the most common metabolic disorders in the world, characterized by the accumulation of excess fat in the body. Research into natural compounds to improve obesity has become increasingly important. Aims and Objectives: The aim of the study was to explore the effects of Sardina pilchardus and Ricinodendron heudelotii oils on the management of obesity. Materials and Methods: Njansan (R. heudelotii) oil was extracted by cold pressing using an automatic oil press machine and Sardine fish oil by a cooking method. To evaluate the anti-obesity effect of these oils, six groups of six male Wistar rats were fed different diets: C0 group received a normal diet; HFD was fed a high-fat diet; N1, N2, F1 and F2 followed by a high-fat diet supplemented with njansan and sardine oils at 1 g/kg body weight/day and 2 g/kg body weight/day, respectively. Results: There was an increase in body weight, relative abdominal fat, and liver weight in the HFD group compared to the control group. There was also a decrease in anthropometric parameters such as the Lee index of the HFD group treated with njansan and fish oils, regardless of the concentration. The hyperlipidemic state in the HFD-fed rats was then normalized after treatment with both oils as well as hyperglycemia compared to the control group. Besides, fish and njansan oils attenuated HFD-induced oxidative stress, as indicated by a significant increase CA and superoxide dismutase. Conclusion: This study demonstrated that njansan oils at a low daily dose (1 g/kg body weight) can be helpful in managing obesity and also reduce the risk of developing coronary heart diseases.

The role of α-lipoic acid in the treatment of patients with gastroesophageal reflux disease against the background of type 2 diabetes mellitus

Objective — to study the role of α‑lipoic acid (ALA) in the treatment of patients with gastroesophageal reflux disease (GERD) in combination with type 2 diabetes mellitus (T2DM).
 Materials and methods. The study involved 120 subjects, who were divided into four groups: 1st group included 60 patients with GERD against the background of T2DM, 2nd group consisted of 20 patients with GERD and 3rd group included 20 patients with isolated T2DM. Additionally, the 1st group was divided into 2 subgroups: 25 patients receiving standard treatment and 29 patients receiving standard treatment + ALA supplementation. The control group consisted of 20 practically healthy age‑matching subjects. Ghrelin and leptin levels were determined by enzyme‑linked immunosorbent assay (ELISA) on the analyzer «Labline‑90» (Austria).
 Results. The comparison of the standard treatment regimen and proposed treatment demonstrated significantly lower frequency of such symptoms as epigastric pain, regurgitation and symptoms, specific for ischemic heart disease, in the subgroup with the proposed treatment regimen (p <0.05). Investigation of carbohydrate and lipid metabolism in a subgroup of patients receiving standard treatment, showed improvements in all parameters, but significant (p <0.05) improvement in patients on the standard therapy was recorded in glucose, insulin, glycosylated hemoglobin (HbA1C) levels, and insulin resistance index (HOMA‑IR). In the subgroup receiving ALA, improvement was gained in the indices of glucose, glycosylated hemoglobin, HOMA‑IR, triglycerides, cholesterol, high and very low‑density lipoproteins and atherogenicity coefficient. After the treatment in the subgroups of standard therapy and therapy with the ALA addition, an increase in ghrelin levels was registered from 0.99±0.41 to 1.09±0.45 ng/ml and from 0.93±0.52 to 1.22±0.59 ng/ml, respectively, and decrease in leptin levels from 19.04±9.48 to 16.66±7.14 ng/ml and from 20.75±9.09 to 16.39±6.88 ng/ml. However, in the first subgroup, the difference between the indicators before and after treatment did not reach the level of statistical significance (p=0.421 and p=0.320, respectively), while in the subgroup where ALA was used, the difference was significant (p <0.05).
 Conclusions. It has been established that ALA positively influences on the state of carbohydrate and lipid metabolism, improving these parameters. The addition of ALA to the standard treatment for GERD against the background of type 2 diabetes showed significant improvement in the studied parameters. Since reference values for ghrelin and leptin levels have not been established yet, it can be assumed that increase in ghrelin and decrease in leptin levels against the background of decrease in well‑studied parameters of lipid and carbohydrate metabolism, have a positive impact on the clinical manifestation of GERD against T2DM background. This assumption may be used as a marker for effective treatment of GERD in combination with T2DM.

The structural characterization of a novel Chinese yam polysaccharide and its hypolipidemic activity in HFD-induced obese C57BL/6J mice

Obesity was considered as a rapidly growing chronic disease that influences human health worldwide. In this study, we investigated the primary structure characteristics of Chinese yam polysaccharide (CYP) and its role in regulating lipid metabolism in a high-fat diet (HFD)-fed obese mice. The molecular weight of CYP was determined to be 3.16 × 103 kDa. Periodic acid oxidation & smith degradation and nuclear magnetic resonance results suggested that CYP consists of 1 → 2, 1 → 2, 6, 1 → 4, 1 → 4, 6, 1→, or 1 → 6 glycoside bonds. The in vivo experiment results suggested that the biochemical indices, tissue sections, and protein regulation associated with lipid metabolism were changed after administering CYP in obese mice. In addition, the abundances of short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Lachnospiraceae_NK4A136_group, and Ruminococcaceae_UCG-014 were increased, and the abundances of bacteria Desulfovibrionaceae and Ruminococcus and metabolites of arginine, propionylcarnitine, and alloisoleucine were decreased after CYP intervention in obese mice. Spearman's correlation analysis of intestinal flora, metabolites, and lipid metabolism parameters showed that CYP may affect lipid metabolism in obese mice by regulating the intestinal environment. Therefore, CYP may be used as a promising nutritional intervention agent for lipid metabolism.

The Degree of Inulin Polymerization Is Important for Short-Term Amelioration of High-Fat Diet (HFD)-Induced Metabolic Dysfunction and Gut Microbiota Dysbiosis in Rats.

Inulin, a non-digestible polysaccharide, has gained attention for its prebiotic properties, particularly in the context of obesity, a condition increasingly understood as a systemic inflammatory state linked to gut microbiota composition. This study investigates the short-term protective effects of inulin with different degrees of polymerization (DPn) against metabolic health deterioration and gut microbiota alterations induced by a high-fat diet (HFD) in Sprague Dawley rats. Inulin treatments with an average DPn of 7, 14, and 27 were administered at 1 g/kg of bodyweight to HFD-fed rats over 21 days. Body weight, systemic glucose levels, and proinflammatory markers were measured to assess metabolic health. Gut microbiota composition was analyzed through 16S rRNA gene sequencing. The results showed that inulin27 significantly reduced total weight gain and systemic glucose levels, suggesting a DPn-specific effect on metabolic health. The study also observed shifts in gut microbial populations, with inulin7 promoting several beneficial taxa from the Bifidobacterium genera, whilst inducing a unique microbial composition compared to medium-chain (DPn 14) and long-chain inulin (DPn: 27). However, the impact of inulin on proinflammatory markers and lipid metabolism parameters was not statistically significant, possibly due to the short study duration. Inulin with a higher DPn has a more pronounced effect on mitigating HFD-induced metabolic health deterioration, whilst inulin7 is particularly effective at inducing healthy microbial shifts. These findings highlight the benefits of inulin as a dietary adjuvant in obesity management and the importance of DPn in optimizing performance.

G protein-coupled receptor 146: new insights from genetics and model systems.

Atherosclerotic cardiovascular diseases continue to be a significant global cause of death. Despite the availability of efficient treatments, there is an ongoing need for innovative strategies to lower lipid levels, especially for individuals experiencing refractory dyslipidemias or intolerable adverse effects. Based on human genetic findings and on mouse studies, the G protein-coupled receptor 146 (GPR146) emerges as a promising target against hypercholesterolemia and atherosclerosis. The present review aims at providing a thorough summary of the latest information acquired regarding GPR146, encompassing genetic evidence, functional insights, and its broader implications for cardiometabolic health. Human genetic studies uncovered associations between GPR146 variants, plasma lipid levels and metabolic parameters. Additionally, GPR146's influence extends beyond lipid regulation, impacting adipocyte differentiation, lipolysis, and inflammation pathways. Despite GPR146's orphan status, ongoing efforts to deorphanize it, suggest a potential ligand with downstream effects involving Gαi coupling. Here, we outline and deliberate on recent progress focused on: enhancing comprehension of the effects of inhibiting GPR146 in humans through genetic instruments, evaluating the extra-hepatic functions of GPR146, and discovering its natural ligand(s). Grasping these biological parameters and mechanisms is crucial in the exploration of GPR146 as a prospective therapeutic target.

A mediation analysis of the role of total free fatty acids on pertinence of gut microbiota composition and cognitive function in late life depression

BackgroundExtensive evidence demonstrates correlations among gut microbiota, lipid metabolism and cognitive function. However, there is still a lack of researches in the field of late-life depression (LLD). This research targeted at investigating the relationship among gut microbiota, lipid metabolism indexes, such as total free fatty acids (FFAs), and cognitive functions in LLD.MethodsTwenty-nine LLD patients from the Cognitive Outcome Cohort Study of Depression in Elderly were included. Cognitive functions were estimated through the Chinese version of Montreal Cognitive Assessment (MoCA). Blood samples were collected to evaluate serum lipid metabolism parameters. Fecal samples were evaluated for gut microbiota determination via 16S rRNA sequencing. Spearman correlation, linear regression and mediation analysis were utilized to explore relationship among gut microbiota, lipid metabolism and cognitive function in LLD patients.ResultsSpearman correlation analysis revealed significant correlations among Akkermansia abundance, total Free Fatty Acids (FFAs) and MoCA scores (P < 0.05). Multiple regression indicated Akkermansia and total FFAs significantly predicted MoCA scores (P < 0.05). Mediation analysis demonstrated that the correlation between decreased Akkermansia relative abundance and cognitive decline in LLD patients was partially mediated by total FFAs (Bootstrap 95%CI: 0.023–0.557), accounting for 43.0% of the relative effect.ConclusionThese findings suggested a significant relationship between cognitive functions in LLD and Akkermansia, as well as total FFAs. Total FFAs partially mediated the relationship between Akkermansia and cognitive functions. These results contributed to understanding the gut microbial-host lipid metabolism axis in the cognitive function of LLD.

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study

BackgroundContinued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism.MethodsThis single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined.ResultsSixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline.ConclusionsSwitching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.