Reduced Serum Triglyceride Research Articles

The Potential of Dehydrated Geniotrigona thoracica Stingless Bee Honey against Metabolic Syndrome in Rats Induced by a High-Carbohydrate, High-Fat Diet

Background/Objectives: Metabolic syndrome (MS) is diagnosed when at least three out of five key risk factors are present: obesity, high blood pressure, insulin resistance, high triglycerides (TG) and low high-density lipoprotein (HDL). MS is often associated with chronic low-grade inflammation. Recent studies have shown that raw stingless bee honey (SBH) can alleviate MS risk factors. However, the high moisture content in raw SBH predisposes it to fermentation, which can degrade its quality. Therefore, dehydrating SBH is necessary to prevent the fermentation process. This study aimed to compare the effects of dehydrated (DeGT) and raw (RGT) SBH from Geniotrigona thoracica species on high-carbohydrate, high-fat diet (HCHF)-induced MS in rats. Methods: Twenty-four male Wistar rats were divided into four groups: control (C), HCHF-induced MS without treatment (MS), HCHF-induced MS treated with DeGT (MS+DeGT) and HCHF-induced MS treated with RGT (MS+RGT). Group C received standard rat chow, while the other groups were fed with HCHF diet for 16 weeks. In the final eight weeks, two HCHF-induced groups received their respective SBH treatments. Results: Both DeGT and RGT treatments reduced energy intake, fat mass, high blood pressure, inflammatory (tumour necrosis factor-alpha (TNF-α)) and obesity (the leptin/adiponectin (L/A) ratio, corticosterone, 11 beta-hydroxysteroid dehydrogenase type-1 (11βHSD1)) markers, as well as prevented histomorphometry changes (prevented adipocyte hypertrophy, increased the Bowman’s space area and glomerular atrophy). Additionally, DeGT increased serum HDL levels, while RGT reduced serum TG, leptin and other inflammatory markers (interleukin-6 (IL-6) and interleukin-1 beta (IL-1β)), as well as hepatosteatosis. Conclusions: While DeGT demonstrates potential as a preventive agent for MS, RGT exhibited more pronounced anti-MS effects in this study.

Lysophospholipid Supplementation in Broiler Breeders' Diet Benefits Offspring's Productive Performance, Blood Parameters, and Hepatic β-Oxidation Genes.

The present study aimed to investigate whether supplementation of modified lysophospholipids (LPLs) in the diet of broiler breeders can benefit their offspring. A total of 264 49-week-old breeders (Ross 308) were allocated and fed based on a 2 × 2 factorial arrangement with two levels of dietary energy (normal energy = 2800 kcal/kg and low energy = 2760 kcal/kg) and two LPL levels (0 and 0.5 g/kg) for periods of 8 and 12 weeks. The offspring were assessed for growth performance, serum parameters, hepatic antioxidative capability, and expression of genes involved in liver β-oxidation at 7 days old. The LPL inclusion improved (p < 0.01) average body weight (ABW), average daily gain (ADG), and feed conversion ratio (FCR). The offspring of 61-week-old breeders fed with LPL exhibited reduced serum triglyceride levels (p < 0.01) but an increase in hepatic glutathione peroxidase (p < 0.05). The LPL increased (p < 0.001) the mRNA expression of the PGC-1α gene in the liver. Supplementing LPL in low-energy diets resulted in higher FABP1 gene expression (p < 0.05) in the intestine. In conclusion, LPL supplementation in the breeders' diet improved offspring performance by enhancing fatty acid absorption, hepatic indices, and the expression of genes involved in liver β-oxidation.

Impact of Conversion from Conventional Pemafibrate to Novel Pemafibrate XR on Hypertriglyceridemia: An Observational Retrospective Study

Background: Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator, which was demonstrated to reduce serum triglyceride levels with few drug-related adverse events in several clinical studies, as well as phase II and III clinical trials. One of the limitations of this medicine was the requirement of twice-daily oral administration, resulting in reduced medication adherence, particularly in elderly patients, who are rather good targets for this medicine. Recently, a once-daily extended-release (XR) tablet has been introduced. Given an improvement in medication adherence, the therapeutic efficacy of pemafibrate may be enhanced. Methods: Patients with hypertriglyceridemia, in whom conventional twice-daily immediate-release (IR) pemafibrate was converted to pemafibrate XR between 2023 and 2024, were eligible. Each type of tablet was prescribed for three months, respectively. A dose change was not attempted. The serum triglyceride levels were compared between 3 months pre-conversion and 3 months post-conversion using a Friedman test and a post hoc Wilcoxon signed-rank test. Results: A total of 46 patients were included. The median age was 62 years, and 29 were men. IR was continued for 698 (280, 1183) days before the conversion. During the last 3-month IR therapy, serum triglyceride levels remained unchanged from 171 (138, 239) mg/dL to 181 (123, 245) mg/dL (p = 0.78). Following the conversion, no patients had drug-related adverse events, and all patients completed 3-month XR therapy. At three months after the conversion, the serum triglyceride levels decreased significantly from 181 (123, 245) mg/dL to 146 (107, 184) mg/dL (p &lt; 0.001). Conclusions: Pemafibrate XR might be a more promising medication than conventional IR in improving hypertriglyceridemia, probably due to improved medication adherence.

AMPK-Mediated Hypolipidemic Effects of a Salvia miltiorrhiza and Paeonia lactiflora Mixed Extract on High-Fat Diet-Induced Liver Triglyceride Accumulation: An In Vivo and In Vitro Study.

This study investigates the hypolipidemic effects of a mixed extract of Salvia miltiorrhiza and Paeonia lactiflora (USCP119) in HFD-fed hamsters and in vitro cellular models. Over an 8-week period, HFD-fed hamsters were assigned to one of six groups: normal diet, HFD control, HFD with 50 mg/kg USCP119, HFD with 100 mg/kg USCP119, HFD with 50 mg/kg USCP119 twice daily (BID), and HFD with omega-3 fatty acids. Key outcomes assessed included body weight, serum triglycerides (TG), total cholesterol (TC), liver weight, hepatic TG levels, and epididymal fat. In cellular models, the impact of USCP119 on lipid accumulation and adipogenic markers was evaluated. USCP119 treatment at 50 mg/kg BID resulted in the lowest weight gain (15.5%) and the most significant reductions in serum TG and hepatic TG levels compared to the HFD control. The 100 mg/kg dose also led to substantial reductions in serum TG and TC levels and notable decreases in low-density lipoprotein cholesterol. USCP119 at 50 mg/kg once daily reduced TG and TC levels but was less effective than the higher doses. In cellular models, USCP119 was non-toxic up to 400 µg/mL and effectively reduced lipid accumulation, modulated adipogenic markers, and enhanced AMPK signaling, improving lipid metabolism and insulin sensitivity. All USCP119 treatments demonstrated effectiveness in managing hyperlipidemia and related metabolic disorders, with variations in impact depending on the dosage. The ability of USCP119 to reduce fat accumulation, improve lipid profiles, and enhance insulin sensitivity highlights its potential as a valuable dietary supplement for addressing high-fat diet-induced hyperlipidemia and metabolic disturbances.

Comparative efficacy of therapeutic plasma exchange and insulin in hypertriglyceridemia-induced acute pancreatitis.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) presents a therapeutic challenge with no currently definitive treatment, including therapeutic plasma exchange (TPE) and insulin. TPE aims to quickly reduce serum triglyceride (TG); however, its efficacy lacks convincing evidence. Intravenous insulin is a promising and convenient alternative, while comparative data is limited. This retrospective, single-center study compared TPE and insulin treatment in HTG-AP patients. The primary outcome measured was the percentage of TG reduction within 48hours of admission. The study included 33 TPE-treated and 56 insulin-treated patients. The TPE groups were more severe than those with medical therapy at baseline characteristics. A trend towards higher TG reduction within 24hours was observed in the TPE group (62.5% [IQR 51.7-83.3] vs. 55.7% [IQR 34.2-74.7], p = 0.038). However, no significant difference in TG reduction at 48hours was found between insulin and TPE groups (83.6% and 81.9%, respectively, p = 0.715). The TPE group exhibited extended hospital stays (10.0 [IQR 7.0-13.5] days vs. 6.0 [4.0-8.7] days, p = 0.001) without any difference in in-hospital mortality or time needed to lower TG below < 11.3mmol/L. In patients with HTG-AP, TPE decreased plasma triglyceride levels faster in the first 24hours than insulin therapy. However, there was no significant advantage after 48hours. Therefore, insulin may be a promising alternative and convenient treatment in carefully selected patients with HTG-AP.

Reducing cardiovascular risk - are omega 3 fatty acids the solution?

Introduction and objective Omega-3 fatty acids possess numerous physiological characteristics, including anti-inflammatory, lipid-lowering, antiarrhythmic, and antithrombotic effects. There has been an ongoing discussion about their potential positive effects on human health and the extent of their influence. In this review, we will explore the current understanding of how omega-3 fatty acids impact the development of cardiovascular diseases. Review methods A review of publications on the effects of omega 3 fatty acids was conducted using the PubMed platform. The main keywords used in the search were "omega 3 fatty acids" and "cardiovascular diseases". The search included a review of the latest scientific work on the effects of omega 3 fatty acids on the body. Abbreviated description of the state of knowledge Omega-3 fatty acids exhibit diverse molecular mechanisms that are beneficial in combating cardiovascular diseases. Reducing serum triglycerides is one of the ways in which omega 3 fatty acids have an advantageous effect on the cardiovascular system. Dietary sources and supplementation offer potential benefits. Summary Omega-3 fatty acids, including EPA and DHA, exhibit various molecular mechanisms such as antithrombotic, anti-inflammatory, and lipid-lowering effects, which are crucial in combating CVDs. Dietary sources of omega-3 include both animal and plant products. Supplementing with omega-3 fatty acids, particularly in patients with elevated triglyceride levels, can significantly reduce CVD risk factors and mortality rates. Recommendations suggest consuming 2 servings of fish per week or supplementing with DHA + EPA to support cardiovascular health. Despite some controversies in research findings, omega-3 supplementation remains beneficial. Ongoing research continues to explore the optimal use and efficacy of omega-3 fatty acids in cardiovascular health.

Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. In this trial, 97 out of 100 randomized participants (mean age: 64.65±4.84years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3months of intervention, significant improvements in waist circumference (83.48±10.22 vs. 82.5±9.88 vs. 82.37±9.42cm, P for trend=0.046), 6-min walking distance (525.65±58.46 vs. 534.47±51.87 vs. 552.02±57.66m, P for trend=0.001), five-time sit-to-stand time (7.63±1.63 vs. 6.81±1.8 vs. 6.4±1.42s, P for trend <0.001), grip strength (26.74±6.54 vs. 27.53±6.99 vs. 28.52±7.09kg, P for trend <0.001), and MNA score (26.8±2.14 vs. 27.73±1.74 vs. 27.55±1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32±49.84 vs. 101.36±42.58 vs. 93.43±41.49mg/dL, P for trend=0.023), increased HDL-C (60.04±16.21 vs. 60±17.37 vs. 62.55±18.27mg/dL, P for trend=0.02), and DHEA-S levels (97.11±54.39 vs. 103.39±56.75 vs. 106.83±60.56μg/dL, P for trend=0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88±5811.68 vs. 11508.97±7151.08 vs. 11220.80±7190.71pg/mL, P for trend=0.016) in controls. The intervention group showed greater improvements in 6min walking distance (β=0.71, 95% CI: 6.88 to 40.79, P=0.006), five-time sit-to-stand test (β=-0.87, 95% CI: -1.59 to -0.15, P=0.017), MNA score (β=0.96, 95% CI: 0.20 to 1.71, P=0.013), serum triglycerides (β=-15.01, 95% CI: -27.83 to -2.20, P=0.022), LDL-C (β=-9.23, 95% CI: -16.98 to -1.47, P=0.020), and DHEA-S levels (β=9.98, 95% CI: 0.45 to 19.51, P=0.04) than controls. Protein-enriched soup with weekly exercise over 12weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

MTORC2 knockdown mediates lipid metabolism to alleviate hyperlipidemic pancreatitis through PPARα.

Hyperlipidemic pancreatitis (HP) is an inflammatory injury of the pancreas triggered by elevated serum triglyceride (TG) levels. The mechanistic target of rapamycin (mTOR) signaling pathway plays a crucial role in regulating lipid homeostasis and inflammation. This study aimed to investigate whether the activity of mTOR complex 2 (mTORC2) affects the progression of HP and its underlying mechanisms. In vivo, a high-fat diet and retrograde administration of sodium taurocholate were employed to establish theHP models in rats, with pancreatic tissue pathology evaluated. The expression of Rictor and peroxisome proliferator-activator receptor (PPAR) was examined. The serum levels of TG, fatty acid metabolites, inflammatory and lipid metabolism-related factors were determined. In vitro, pancreatic acinar cells (PACs) were exposed to palmitic acid and cholecystokinin-8. PAC apoptosis, pyroptosis, and ferroptosis were assessed. In the HP models, rats and PACs exhibited upregulated Rictor and downregulated PPARα, and Rictor knockdown promoted PPARα expression. In vivo, Rictor knockdown decreased the serum levels of TG, α-amylase, total cholesterol, low-density lipoprotein cholesterol, lactate dehydrogenase, and inflammatory factors, while increasing high-density lipoprotein cholesterol levels. Rictor knockdown increased ACOX1 and CPT1α and decreased SREBP-1, CD36, SCD1, ACLY, and ACACA. Rictor knockdown reduced damage to pancreatic tissue structure. In vitro, Rictor knockdown inhibited PAC apoptosis, pyroptosis, and ferroptosis. Treatment with the PPARα antagonist GW6471 abolished the beneficial effects of Rictor knockdown. Rictor/mTORC2 deficiency reduces serum TG levels, maintains lipid homeostasis, and suppresses inflammation by inhibiting PPARα expression. Weakening mTORC2 activity holds promise as a novel therapeutic strategy for HP.

Effect of Palmitoylethanolamide Compared to a Placebo on the Gut Microbiome and Biochemistry in an Overweight Adult Population: A Randomised, Placebo Controlled, Double-Blind Study.

This study investigates the effects of palmitoylethanolamide (PEA) on the gut microbiome of overweight adults. Fifty-eight participants (twenty males, thirty-eight females) aged 18-65 years with a BMI range of 30-40 kg/m2 were recruited. Participants were randomised to receive PEA (n = 36) or a placebo (n = 22) for 12 weeks. Microbiota composition, richness, diversity, and metabolic functions, faecal short chain fatty acids and calprotectin, pathology markers, and health-related questionnaires were analysed throughout the 12 weeks of supplementation. PEA supplementation significantly reduced triglyceride levels and IL-2 concentrations. No significant differences were found in the overall microbiota composition between the groups, and microbiota richness and diversity remained consistent for both groups. Functional analysis demonstrated no differences in functional richness and diversity, but specific pathways were modified. PEA supplementation resulted in a decrease in the abundance of pathways related to aromatic compound degradation, NAD interconversion, and L-glutamate degradation, while pathways associated with molybdopterin biosynthesis and O-antigen building blocks exhibited increased abundance. Increased production of O-antigen results in smooth LPS associated with reduced pathogenic stealth and persistence. PEA supplementation may influence specific microbial species, metabolic pathways, and reduce serum triglyceride and IL-2 concentration, shedding light on the intricate relationship between PEA, the microbiome, and host health.

Inhibition of FoxO1 ameliorates hepatic steatosis and hepatitis in nonalcoholic steatohepatitis mice through regulation of gut microbiota.

We aimed to investigate the role of forkhead box O1 (FoxO1) inhibitor AS1842856 (AS) in nonalcoholic steatohepatitis (NASH) mice and the potential mechanisms. Mice were given methionine-choline-sufficient (MCS), or methionine- and choline-deficient (MCD) diet for 5 weeks, along with AS (60 mg/kg) or vehicle gavage treatment (0.2 mL/day). Body and liver weight, serum triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose and insulin levels were measured. Liver macrophage infiltration and ileal ZO-1 protein expression were also detected. Interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, sterol regulatory element binding protein (SREBP)-1c, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase), α-smooth muscle actin (SMA), recombinant collagen type III α1 (Col3a1), and connective tissue growth factor (Ctgf) expressions were measured. Stool samples were collected for 16S rDNA sequencing. Compared to the MCD group, AS attenuated liver weight, reduced serum TG, ALT, and AST levels, increased HDL-C levels, mitigated hepatic steatosis, decreased macrophage infiltration, and augmented ileal ZO-1 proteins in NASH mice. It also reduced the levels of IL-6, IL-1β, and TNF-α, alongside with the Srebp-1c mRNA expression. However, no significant effects on Pepck, G6Pase, α-SMA, Col3a1, or Ctgf were observed. Furthermore, AS promoted diversity and altered gut microbiota composition in NASH mice, causing increased beneficial bacteria like Akkermansia muciniphila, Parabacteroides distasonis, and Prevotellamassilia, which were associated with metabolic functions. FoxO1 inhibitor AS ameliorated hepatic steatosis, inflammation, and intestinal dysbiosis in NASH mice, making it a potentially promising treatment for NASH.

Tratamiento de la hipertrigliceridemia grave mediante recambio plasmático terapéutico en pacientes con pancreatitis aguda o en riesgo de padecerla

Introduction and objectivesTPE drastically reduces serum triglyceride (sTG), but its role in the treatment of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) or at risk of developing it, is not well established. The objectives were to assess the effectiveness and safety of TPE in the treatment of severe HTG (sHTG), as well as to evaluate the severity of HTG-AP treated with TPE. Materials and methodsObservational-retrospective-single-center study, in which a descriptive analysis of sHTG treated with TPE was conducted, with the aim of treating HTG-AP or preventing its recurrence. TPE was performed if sTG≥ 1000 mg/dL after 24 hours of admission. Results42 TPE were performed to treat 35 sHTG in 23 patients: 29 HTG-AP, and 6 sHTG with previous HTG-AP. Among the patients, 37% (13/55) were women, with 37 ± 14 years-old, 74.3% had normal BMI (25/35), 34% (12/35) were drinking > 40 g/alcohol/day and 54% (19/35) were diabetics. TPE significantly reduced the baseline sTG (4425 ± 2782 mg/dL vs. 709 ± 353 mg/dL, p < 0.001) in a single session, achieving a mean percentage reduction of 79 ± 13%; 20% (7/35) of sHTG cases required two TPE sessions to reduce sTG to < 1000 mg/dL. Adverse effects were reported in 4/42 TPE sessions (9,5%). sHTG-AP was observed in 3% of cases (1/29), and there were no deaths. sTG at 24 hours of admission showed no relation with the severity of APs. ConclusionThe treatment of sHTG with TPE, with the aim of treating HTG-AP or preventing its recurrence, reduces sTG quickly and safety.

Evaluation of chapattis fortified-diet with raw and fermented carrot powder in persons with type 2 diabetes: A randomized control pilot study

BackgroundDiabetes is a metabolic disease that is common and growing rapidly. It is characterised by high blood sugar levels and related complications to vital organs such as the kidneys, heart, blood vessels, and eyes. The most common kind of diabetes affecting people globally is type 2 diabetes (T2D). An increasing number of people are looking at natural foods and dietary supplements to manage their T2D.ObjectiveThe aim of this pilot study was to assess the glycemic index, glycemic response, sensory qualities, nutritional composition, and possible antidiabetic benefits of chapattis fortified with raw and fermented carrot powder.MethodsSeven preparations of chapattis were prepared into three variants from whole wheat flour chapattis (WWFC) as control group, raw carrot-supplemented chapattis (RCSC) with subtypes T1, T2, and T3, and fermented carrot-supplemented chapattis (FCSC) with subtypes T4, T5, and T6. The variants were provided to 11 professionally trained sensory panelists for organoleptic evaluation. The chapattis subtype with the best organoleptic properties together with the WWFC were then given randomly to a group of 30 persons with T2D respectively to see how their blood sugar levels were affected over a period of 4 weeks.Results The panelist adjudged RCSC (T2) and FCSC (T5) as the best organoleptically. The randomised control investigation demonstrated that the fasting blood glucose levels for WWFC, RCSC, and FCSC decreased (P&lt;0.05) significantly by 6.42%, 7.24%, and 12.75%, respectively. However, there was no significant different in the fasting blood sugar between the WWFC and RCSC. As for the glycemic load values of WWC, RCSC, and FCSC, which were 21, 14, and 13, respectively, there was no statistically significant difference between RCSC and FCSC, suggesting that both types of chapattis could help T2D patients regulate their blood sugar levels. The most significant changes were consistently shown by the FCSC: 17.50% reduction in random blood sugar (p = 0.03), 21.85% reduction in serum low-density lipoprotein (p = 0.051), 16.67% increase in serum HDL (p = 0.01), 11.09% decrease in serum cholesterol (p = 0.02), and 12.575% reduction in serum triglycerides (p = 0.048).ConclusionsA beneficial dietary intervention for people with T2D may involve mixing fermented carrot powder into regular chapattis. These findings contribute to the growing body of evidence in favour of using natural food-based treatments for the management of diabetes.

Dietary sugar kelp (Saccharina latissima) consumption did not attenuate atherosclerosis in low-density lipoprotein receptor knockout mice.

We previously demonstrated the beneficial effects of U.S.-grown sugar kelp (Saccharina latissima), a brown seaweed, on reducing serum triglycerides (TG) and total cholesterol (TC) and protecting against inflammation and fibrosis in the adipose tissue of diet-induced obesity mice. In this current study, we aimed to explore whether the dietary consumption of sugar kelp can prevent atherosclerosis using low-density lipoprotein receptor knockout (Ldlr KO) mice fed an atherogenic diet. Eight-week-old male Ldlr KO mice were fed either an atherogenic high-fat/high-cholesterol control (HF/HC) diet or a HF/HC diet supplemented with 6% (w/w) sugar kelp (HF/HC-SK) for 16 weeks. Consumption of sugar kelp significantly increased the body weight gain without altering fat mass and lean mass. Also, there were no significant differences in energy expenditure and physical activities between the groups. The two groups did not show significant differences in serum and hepatic TG and TC levels or the hepatic expression of genes involved in cholesterol and lipid metabolism. Although serum alanine aminotransferase (ALT) activity did not differ significantly between the two groups, there were significant increases in the expression of macrophage markers, including adhesion G protein-coupled receptor E1 and cluster of differentiation 68, as well as tumor necrosis factor alpha in the HF/HC-SK group compared to the HF/HC mice. The consumption of sugar kelp did not elicit a significant effect on the development of aortic lesions. Moreover, lipopolysaccharide-stimulated splenocytes isolated from HF/HC-SK-fed mice showed no significant changes in the mRNA levels of pro-inflammatory genes compared with those from the HF/HC mice. In summary, the consumption of dietary sugar kelp did not elicit anti-atherogenic and hepatoprotective effects in Ldlr KO mice.

Arsenic exposure at environmentally relevant levels induced metabolic toxicity in development mice: Mechanistic insights from integrated transcriptome and metabolome

Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.

A commensal-derived sugar protects against metabolic disease.

Obesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human-derived commensal bacterium, Clostridium immunis , that protects against metabolic disease by secreting a phosphocholine-modified exopolysaccharide. Genetic interruption of the phosphocholine biosynthesis locus ( licABC ) results in a functionally inactive exopolysaccharide, which demonstrates the critical requirement for this phosphocholine moiety. This C. immunis exopolysaccharide acts via group 3 innate lymphoid cells and modulating IL-22 levels, which results in a reduction in serum triglycerides, body weight, and visceral adiposity. Importantly, phosphocholine biosynthesis genes are less abundant in humans with obesity or hypertriglyceridemia, findings that suggest the role of bacterial phosphocholine is conserved across mice and humans. These results define a bacterial molecule-and its key structural motif-that regulates host metabolism. More broadly, they highlight how small molecules, such as phosphocholine, may help fine-tune microbiome- immune-metabolism interactions.

Clinical value of adding Dapagliflozin in patients with nephrotic syndrome.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors in nephrotic patients on immunosuppression are underexplored. We evaluated dapagliflozin's impact in non-diabetic primary nephrotic syndrome. Randomized controlled clinical trial was conducted on 60 non-diabetic primary nephrotic syndrome patients, equally assigned to dapagliflozin and control groups. All patients received the standard of care medication and the Dapagliflozin group received 10mg dapagliflozin in addition. Demographic data, nephrotic syndrome etiology, proteinuria levels, eGFR, and immunosuppression doses, were well-matched. After 6months of follow up primary outcomes included changes in and eGFR. Both groups exhibited significant reductions in proteinuria after 6months, with the dapagliflozin group achieving a mean UPCR reduction of - 94.7%, and the control group - 86.7% (p < 0.001). However, the comparative change in proteinuria between both groups did not reach statistical significance (p = 0.158). Dapagliflozin initially led to a transient eGFR decline. Dapagliflozin also resulted in a significant mean body weight reduction (p < 0.001) and notable improvements in triglyceride levels compared to the control group (p = 0.045). In primary nephrotic syndrome patients, adjunct dapagliflozin may enhance the standard of care. While notable, the reduction in proteinuria was comparable to that of the control group by the study's end. Furthermore, after 6months, eGFR remained stable in both groups. However, significant weight loss and serum triglyceride reduction were particularly pronounced in the dapagliflozin group. Further long-term investigations are necessary to address potential immunosuppression-related confounding effects in patients with primary glomerular disease.

Low-Iron Diet-Induced Fatty Liver Development Is Microbiota Dependent and Exacerbated by Loss of the Mitochondrial Iron Importer Mitoferrin2.

Iron deficiency is the number one nutritional problem worldwide. Iron uptake is regulated at the intestine and is highly influenced by the gut microbiome. Blood from the intestines drains directly into the liver, informing iron status and gut microbiota status. Changes in either iron or the microbiome are tightly correlated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD). To investigate the underlying mechanisms of the development of MASLD that connect altered iron metabolism and gut microbiota, we compared specific pathogen free (SPF) or germ-free (GF) mice, fed a normal or low-iron diet. SPF mice on a low-iron diet showed reduced serum triglycerides and MASLD. In contrast, GF low-iron diet-fed mice showed increased serum triglycerides and did not develop hepatic steatosis. SPF mice showed significant changes in liver lipid metabolism and increased insulin resistance that was dependent upon the presence of the gut microbiota. We report that total body loss of mitochondrial iron importer Mitoferrin2 (Mfrn2-/-) exacerbated the development of MASLD on a low-iron diet with significant lipid metabolism alterations. Our study demonstrates a clear contribution of the gut microbiome, dietary iron, and Mfrn2 in the development of MASLD and metabolic syndrome.

Recent Advances in the Therapeutic Potential of Carotenoids in Preventing and Managing Metabolic Disorders.

Carotenoids constitute compounds of significant biological interest due to their multiple biological activities, such as antimicrobial, anticancer, antiadipogenic, antidiabetic, and antioxidant properties. Metabolic syndrome (MetS) comprehends a series of metabolic abnormalities (e.g., hypertension, obesity, and atherogenic dyslipidemia) that can affect children, adolescents, and the elderly. The treatment of MetS involves numerous medications, which, despite their efficacy, pose challenges due to prolonged use, high costs, and various side effects. Carotenoids and their derivatives have been proposed as alternative treatments to MetS because they reduce serum triglyceride concentrations, promote insulin response, inhibit adipogenesis, and downregulate angiotensin-converting enzyme activity. However, carotenoids are notably sensitive to pH, light exposure, and temperature. This review addresses the activity of carotenoids such as lycopene, lutein, fucoxanthin, astaxanthin, crocin, and β-carotene towards MetS. It includes a discussion of sources, extraction methods, and characterization techniques for analyzing carotenoids. Encapsulation approaches are critically reviewed as alternatives to prevent degradation and improve the biological performance of carotenoids. A brief overview of the physiopathology and epidemiology of the diseases, including MetS, is also provided.

The Effect of Nelumbo nucifera Ethanolic Extract on Gut Microbiota in Hyperlipidemic Rats Induced by a High-Fat Diet

Objective: This study aimed to assess the effect of Nelumbo nucifera alcoholic extract (LLAE) on the intestinal microbiota in high-fat diet-induced hyperlipidemia. Methods: Thirty male-specific pathogen-free Sprague–Dawley rats were randomly divided into 3 groups: the blank control group, the model control group, and the LLAE group. The body weight of the rats was recorded during the treatment period. The serum, liver, and intestinal content samples were collected for further analysis after sacrificing. Results: The results suggest that LLAE-treated hyperlipidemic rats showed a significant reduction in serum triglycerides, total cholesterols, and low-density lipoprotein cholesterol levels. LLAE could improve hepatocyte steatosis and ameliorate hepatocyte injury. The significant variation in gut microbial alpha diversity at multiple levels, including phylum and genus levels occurred throughout treatment in the LLAE group. The intestinal microbiota of hyperlipidemic rats were disordered, and there was a correlation between the amount of intestinal flora and the level of lipids. Conclusion: LLAE may improve hepatocyte function by changing the type and abundance value of intestinal microorganisms, reducing the content of total cholesterol, total triglyceride, and low-density lipoprotein cholesterol, and thus improving hyperlipidemia.

SLC25A28 Overexpression Promotes Adipogenesis by Reducing ATGL.

Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1α. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.