Regulation Of Lipid Metabolism Research Articles

Efficient synthesis of polydatin by a two-enzyme coupled with one-pot method

Traditional Chinese medicine of Polygonum cuspidatum has been utilized in China for thousands of years. Its primary active compound, polydatin, exhibits a variety of pharmacological effects including the regulation of glucose and lipid metabolism, suppression of cough and asthma, as well as antibacterial and anti-inflammatory properties. However, conventional methods for polydatin production are inadequate to satisfy the market demand. This study aims to explore the green and efficient preparation of polydatin. With resveratrol as the substrate, we efficiently synthesized polydatin by using the triple mutant IGW (Y14I/I62G/M315W) of the glycosyltransferase UGTBS based on a strategy of two-enzyme coupled with one-pot and realized the recycling of uridine diphosphate-glucose (UDPG). The conditions of the two-enzyme reaction were optimized. Under the conditions of 35 ℃, pH 8.0, IGW: AtSuSy1 activity ratio of 3:4, dimethyl sulfoxide (DMSO) volume fraction of 5%, uridine diphosphate (UDP) concentration of 0.10 mmol/L, and sucrose concentration of 0.6 mol/L, the conversion of 2 mmol/L resveratrol reached 80.6% within 1 h, and the proportion of polydatin was over 90%. This study achieved the recycling of UDPG via a two-enzyme coupling system and shortened the reaction time. At the same time, the fed-batch strategy was adopted, and the yield of polydatin reached 6.28 g/L after 24 h in the one-pot coupling reaction, which provided a new strategy for green and efficient preparation of polydatin.

Curcumin enhances the anti-obesogenic activity of orlistat through SKN-1/NRF2-dependent regulation of nutrient metabolism in Caenorhabditis elegans.

Metabolic dysregulation, a defining feature of obesity, disrupts essential signalling pathways involved in nutrient sensing and mitochondria homeostasis. The nuclear factor erythroid 2-related factor 2 (NRF-2) serves as a pivotal regulator of the cellular stress response, and recent studies have implicated it in the pathogenesis of obesity, diabetes, and metabolic syndrome. Curcumin, a polyphenolic compound derived from turmeric, has been identified as a potent activator of NRF-2. Evidence suggests curcumin impacts obesity and metabolic disorders by modulating gut microbiota composition, increasing energy expenditure, and regulating lipid metabolism. Orlistat, an anti-obesity drug, inhibits fat absorption in the gastrointestinal tract, but its side effects limits its broader use. The present study aims to investigate the potential synergetic effect of a hybrid combination between orlistat and curcumin. Additionally, we provide a detailed understanding of the molecular mechanisms through which this combination mitigates glucose-induced lipid accumulation in Caenorhabditis elegans, with a focus on the role of the skinhead 1 (SKN-1) transcription factor, an orthologue of NRF2. We assessed the lipid accumulation and the changes in skn-1 transcriptional activity in C. elegans using confocal GFP-based detection, alongside mRNA expression analysis of genes from lipid metabolism and oxidative stress response in wild-type, QV225 and LD1 strains. Furthermore, we evaluated locomotion, chemotaxis and mitochondrial dynamics to enhance our understanding of the proposed molecular-based model. Our findings reveal that the orlistat/curcumin combination exerts an anti-obesogenic effect through SKN-1/NRF2-dependent regulation of conserved genes involved in carbohydrate and lipid metabolism in C. elegans. Moreover, the combination stimulates mitochondrial potential, further contributing to the observed synergistic effects. The hybrid combination of orlistat and curcumin demonstrates significant anti-obesity activity by regulating nutrient-sensing pathways through SKN-1/NRF-2 modulation. This approach may allow for the reduction of orlistat dosage, thereby minimizing its adverse effects while maintaining its therapeutic efficacy.

Effects of dietary supplementation with butyrate glycerides on lipid metabolism, intestinal morphology, and microbiota population in laying hens.

The present study investigated the impact of butyrate glycerides (BG) on lipid metabolism, intestinal morphology, and microbiota of laying hens. Four hundred eighty 54-week-old Hy-line Brown laying hens were randomly selected and divided into five groups. The control group (ND) was fed a basal diet. Meanwhile, the remaining groups were given a basal supplemented with 0.5, 1, 2, and 4 g/kg of the product containing BG and were designated as BG-0.5, BG-1, BG-2, and BG-4 groups, respectively. The findings showed that: (1) BG supplementation significantly decreased (P < 0.001) the blood Glu levels (BG-0.5, BG-1, BG-2, and BG-4) and increased (P < 0.001) the serum HDL-C levels (BG-2, and BG-4). (2) The BG-2 and BG-4 groups showed an increase (P < 0.01) in abdominal lipid HSL activity. (3) The levels of hepatic TC and TG in all BG groups were significantly decreased (P < 0.05). (4) The addition of BG resulted in a significant reduction in the mRNA expression of the liver X receptor alpha (LXRα) (P < 0.05). (5) All BG groups presented a substantial reduction in duodenal crypt depth and a notable increase in the ratio of villus height to crypt depth (V/C) (P < 0.01). Additionally, all BG groups exhibited a significant increase in villus height in the ileum (P < 0.001). (6) Both the BG-1 and BG-4 groups exhibited a significant reduction in the amounts of n-butyric and n-glutaric acids in the cecum contents (P < 0.05). (7) The inclusion of BG did not substantially impact the diversity of cecal microbiota in laying hens. However, it dramatically boosted the proportion of the beneficial bacterium Alistipes (P < 0.05) and reduced the abundance of the harmful bacterium Verrucomicrobiota (P < 0.05). Overall, incorporating BG with glycerol monobutyrate as the diet's primary active component reduces fat accumulation in laying hens' blood and liver. It potentially regulates lipid metabolism via the PPARγ-LXRα-SREBP1c pathway. Additionally, BG has the potential to enhance the structure of the small intestine's mucous membrane and increase the presence of beneficial bacteria. Under the experimental conditions, late-laying hens supplemented with 4 g/kg BG performed best overall.

Lactobacillus acidophilus YL01 and its exopolysaccharides ameliorate obesity and insulin resistance in obese mice via modulating intestinal specific bacterial groups and AMPK/ACC signaling pathway.

Probiotics intervention by Lactobacillus acidophilus has potential effect on alleviating obesity and insulin resistance. However, the limited knowledge of functional substances and potential regulatory mechanisms hinder their widespread application. Herein, L. acidophilus YL01 was firstly isolated from Chinese traditional yogurt, demonstrating inhibitory activities on amylase and glucosidase that are comparable to those of L. rhamnosus LGG. Besides, the oral administration of L. acidophilus YL01 and its EPS significantly reduced body weight in high-fat mice (p < 0.05), as well as fat accumulation in liver and adipocytes. Moreover, they not only reduced fasting blood glucose and glucose/insulin resistance, but also improved dyslipidemia, liver function and inflammation. Further high-performance liquid chromatography analysis and Fourier transform infrared spectroscopy indicated that EPS is an acidic polysaccharide, characterized by a molecular weight of 952 kDa and predominantly composed of glucose. Additionally, the mechanism investigation revealed that the L. acidophilus YL01 and EPS demonstrated limited efficacy in restoring the composition of gut microbiota, but rather exerted an influence on the abundance of specific bacterial groups. The enrichment of the bacterial groups resulted in the increase of acetic acid and butyric acid, which further mediates the gut-liver crosstalk in regulating lipid metabolism by the activation of AMPK/ACC pathway.

Anti-Obesity Properties of Boesenbergia rotunda Rhizome Extract: Regulation of Inflammation, Lipid Metabolism, and Insulin Signaling in ob/ob Mice

Anti-Obesity Properties of Boesenbergia rotunda Rhizome Extract: Regulation of Inflammation, Lipid Metabolism, and Insulin Signaling in ob/ob Mice

Plasma adiponectin and biomarker-confirmed Alzheimer's disease in a tertiary memory clinic.

Alzheimer's disease (AD) is associated with early metabolic dysfunction and adiponectin, which may play a pathophysiological role. Adiponectin is implicated in the regulation of energy homeostasis, carbohydrate, and lipid metabolism, as well as in inflammation modulation. The aim of this study was to study whether plasma adiponectin levels were different between patients with AD confirmed by biomarkers and neurological control subjects. We performed a monocentric, retrospective, cross-sectional, observational study in AD patients and neurological controls recruited from daily clinical practice in a tertiary memory clinic. Plasma adiponectin levels were measured using a chemiluminescent enzyme immunoassay. We analyzed the relationship between adiponectin and AD using linear regression models including age, gender, and BMI. We also described the distribution of adiponectin concentrations, across age, and gender categories. Two hundred and six patients (142 AD patients and 64 neurological controls) were included, with mean age = 68.8 ± 10.0 years, and 56% were women. Higher adiponectin concentrations were observed in females and in older adults. Plasma adiponectin levels were significantly higher in AD patients (mean = 6.45 ± 3.42 μg/mL) than neurological controls (4.85 ± 3.54 μg/mL) (p < .001). This association was mediated by age, gender, and BMI, which were significantly and independently associated with plasma adiponectin levels (p < .01 for each), while adiponectin was no longer associated with AD in multivariate models. Patients with AD showed higher adiponectin levels, but this association was driven by older age, female gender, and lower BMI in the AD group. Further studies are needed to better characterize the hormonal signature of AD.

Total saponin extracts of Pseudostellaria heterophylla ameliorates meibomian gland dysfunction through SCD1/SPT1/ceramide axis.

Pseudostellaria heterophylla (Tài Zǐ Shēn, TZS) is a traditional Chinese medicine with spleen and qi benefits. Its immunomodulatory, anti-fatigue, anti-stress, and lipid metabolism regulation effects have been clinically confirmed, but its role in meibomian gland dysfunction (MGD) is still unclear. This study aims to investigate the effect and mechanism of action of TZS in treating MGD. Several therapeutic agents were used to predict MGD treatment using the "Disease-Syndrome-TCM" network mechanism. We then performed a network pharmacology analysis to identify possible targets and pathways for drug treatment of the disease. It was then validated by in vitro experiments. The animal models were taken and analyzed by slit lamp and stereo microscope. HE and ORO staining analysis were then performed. Next, the expressions of key protein indicators were tested by IF, and finally the metabolism of key substances such as lipids and ceramides were detected by SRS imaging. The "Disease-Syndrome-TCM" network mechanism was used to predict several therapeutic agents for MGD treatment including TZS et al. Network pharmacology analysis revealed that the targets of active components in the total saponins of TZS (PHS) were significantly enriched in the pathways of PPAR and AMPK. Subsequently, seven targets of PHS were identified, which were enriched in signaling pathways associated with lipid metabolism and inflammation. Furthermore, in vivo experiments showed that PHS alleviated meibomian glands (MG) obstruction and atrophy induced by A939, a SCD1 inhibitor. PHS treatment significantly increased PPAR-γ proteins in MGs, contributing to the normal differentiation of acini. Additionally, PHS treatment resulted in a reduction in the number of K10-positive cells, which partially prevented keratinization and abnormal differentiation of acinar cells. TUNEL assay results indicated that PHS mitigated apoptosis in MGs. Detailed exploration using Raman spectroscopy imaging showed that PHS could enhance the expression of SCD1 protein and the unsaturation degree of fatty acids, which in turn downregulated SPT1 protein and endogenous ceramides de novo biosynthesis. This study elucidated the effects of PHS in alleviating MGD and highlighted the pharmacological mechanisms involved, specifically the upregulation of SCD1 and inhibition of de novo ceramides biosynthesis. These findings provided a research basis for advancing its clinical application in MGD treatment.

Dapagliflozin modulates hepatic lipid metabolism through the proprotein convertase subtilisin/kexin type 9/low density lipoprotein receptor pathway.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is mainly secreted by the liver, and plays a crucial role in lipid metabolism disorder. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can regulate lipid metabolism through various pathways, including reducing visceral fat accumulation, modulating serum lipoprotein levels and alleviating hepatic steatosis. However, the specific regulatory mechanisms remain unclear. We built a model of glucose and lipid metabolism disorder in vivo and in vitro, and explored the regulatory mechanism of dapagliflozin in regulating liver lipid metabolism. We found that the SGLT2i dapagliflozin significantly reduced serum levels of PCSK9, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) in high-fat diet (HFD)-fed mice, while also improving hepatic steatosis. In vitro studies confirmed that dapagliflozin increased LDL receptor (LDLR) expression in HepG2 cells, enhancing their ability to uptake LDL-C. Further mechanistic studies revealed that the hepatocyte nuclear factor-1-alpha (HNF1α)/PCSK9/LDLR signalling pathway may be involved in dapagliflozin's regulation of lipid metabolism homeostasis.

Transcriptome Analysis Reveals the Molecular Mechanism of PLIN1 in Goose Hierarchical and Pre-Hierarchical Follicle Granulosa Cells.

PLIN1, a member of the PAT family, is expressed in both adipocytes and steroidogenic cells. In this study, we used cell transfection technology combined with transcriptome sequencing to investigate the regulatory mechanism of PLIN1 in goose follicular GCs. Gene Ontology (GO) analysis revealed that in the four groups (phGC: over_vs_over-NC; hGC: over_vs_over-NC; phGC: si_vs_si-NC; hGC: si_vs_si-NC), most differentially expressed genes (DEGs) were significantly enriched (p < 0.05) in pathways related to biological processes (BPs), particularly those associated with the regulation of cellular lipid metabolism and oxidative stress. KEGG analysis further identified significant enrichment (p < 0.05) in pathways related to cell apoptosis and the cell cycle. A joint analysis of KEGG and PPI on the upregulated and downregulated DEGs revealed that the TGF-β signaling pathway was the only pathway significantly enriched among both upregulated and downregulated DEGs after PLIN1 overexpression in hGCs and phGCs. Based on these findings, we hypothesize that PLIN1 overexpression may promote granulosa cell proliferation and apoptosis by activating the TGF-β signaling pathway in goose follicular GCs. Additionally, nine potential candidate genes were identified: PPARγ, MGLL, PTEN, BAMBI, BMPR2, JUN, FST, ACSF3, and ACSL4. These results address a significant research gap concerning the role of this gene in granulosa cells and contribute to the understanding of its molecular regulatory mechanisms.

Ganoderma lucidum spore oil attenuates acute liver injury by modulating lipid metabolism and gut microbiota.

The incidence of acute liver injury is increasing and poses a significant threat to human health. Ganoderma lucidum spore oil (GLSO), a lipid substance extracted from Ganoderma lucidum spore powder using supercritical CO2 technology, has been investigated for its potential to prevent acute liver injury. However, the specific mechanism underlying the protective effects of GLSO remains incompletely understood. In this study, we investigated the preventive effect of GLSO on acute liver injury in rats, focusing on the gut microbiome and serum metabolomics. GLSO effectively alleviated liver dysfunction and reduced inflammation, leading to the prevention of acute liver injury in rats. Serum metabolomics analysis revealed that GLSO primarily modulated lipid metabolic pathways related to glycerophospholipid metabolism and sphingolipid metabolism. Specifically, GLSO decreased the levels of metabolites such as lysophosphatidylcholine (LPC), glycerophosphatidylcholine (GPC), and sphinganine 1-phosphate (SA1P), while increasing the levels of phosphatidylglycerol (PG) and digalactosylceramide (DGC). Gut microbiomics data indicated that GLSO effectively regulated the composition of the gut microbiota in rats with acute liver injury. Specifically, it increased the abundance of Firmicutes and decreased the abundance of Proteobacteria. Mantel test correlation analysis revealed a close relationship between gut microbial Burkholderiales and lipid metabolites in GLSO-mediated prevention of acute liver injury. GLSO exerts its preventive effects on acute liver injury by remodeling the gut microbiota and regulating lipid metabolism. These findings provide novel insights and potential directions for the development of new drugs targeting acute liver injury.

Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.

Spinal Muscular Atrophy is an autosomal dominant disease caused by mutations and deletions within the SMN1 gene, with predominantly childhood onset. Although primarily a motor neuron disease, defects in non-neuronal tissues are described in both patients and mouse models. Here, we have undertaken a detailed study of the heart in the Smn2B/- mouse models of SMA, and reveal a thinning of the ventriclar walls as previously described in more severe mouse models of SMA. However most structural changes are resolved by accounting for the smaller body size of the SMA mouse, as was also confirmed in the SMN∆7 model. Echocardiography revealed increased systolic function, which was particularly pronounced in subsets of mice and an increase in global longitudinal strain, collectively indicative of increased cardiac stress in the Smn2B/- mouse model. We have used TMT proteomics to perform a longitudinal study of the proteome of the hearts of Smn2B/- mice and reveal a progressive dysregulation of LXR/RXR signalling which is a regulator of lipid metabolism. We further show consistent perturbations in lipid metabolism in the Smn2B/-, Smn-/-;SMN2;SmnΔ7and SmnΔ7/Δ7;SMN2 mouse models of SMA on the day of birth. This work indicates that although structural changes in the heart can be overstated by failing to account for body size, there are functional defects which could predispose the heart to subsequent failure. We identify a common molecular signature across mouse models pointing to a dysregulation in lipid metabolism, and suggest that manipulation of LXR/RXR signalling offers an opportunity to impact upon these pathways.

Born of frustration: the emergence of Camelina sativa as a platform for lipid biotechnology.

The emerging crop Camelina sativa (L.) Crantz (camelina) is a Brassicaceae oilseed with a rapidly growing reputation for the deployment of advanced lipid biotechnology and metabolic engineering. Camelina is recognised by agronomists for its traits including yield, oil/protein content, drought tolerance, limited input requirements, plasticity and resilience. Its utility as a platform for metabolic engineering was then quickly recognised, and biotechnologists have benefited from its short life cycle and facile genetic transformation, producing numerous transgenic interventions to modify seed lipid content and generate novel products. The desire to work with a plant that is both a model and crop has driven the expansion of research resources for camelina, including increased availability of genome and other "-omics" data sets. Collectively the expansion of these resources has established camelina as an ideal plant to study the regulation of lipid metabolism and genetic improvement. Furthermore, the unique characteristics of camelina enables the design-build-test-learn cycle to be transitioned from the controlled environment to the field. Complex metabolic engineering to synthesize and accumulate high levels of novel fatty acids and modified oils in seeds, can be deployed, tested and undergo rounds of iteration in agronomically relevant environments. Engineered camelina oils are now increasingly being developed and used to sustainably supply, improved nutrition, feed, biofuels and fossil fuel replacements for high-value chemical products. In this review, we provide a summary of seed fatty acid synthesis and oil assembly in camelina, highlighting how discovery research in camelina supports the advance of metabolic engineering towards the predictive manipulation of metabolism to produce desirable bio-based products. Further examples of innovation in camelina seed lipid engineering and crop improvement are then provided, describing how technologies (e.g., genetic modification (GM), gene editing (GE), RNAi, alongside GM and GE stacking) can be applied to produce new products and denude undesirable traits. Focusing on the production of long chain polyunsaturated omega-3 fatty acids in camelina, we describe how lipid biotechnology can transition from discovery to a commercial prototype. The prospects to produce structured triacylglycerol with fatty acids in specified stereospecific positions are also discussed, alongside the future outlook for the agronomic uptake of camelina lipid biotechnology.

Metabolic Reprogramming in Prostate Cancer: The Roles of HOXB13 and FASN in Tumor Progression and Therapy

Metabolic reprogramming, particularly lipid metabolism, is a hallmark of cancer progression and a critical vulnerability in prostate cancer (PCa). Two pivotal studies, one by Lu et al. and the other by Dairo et al., have illuminated the roles of HOXB13, a transcriptional regulator, and fatty acid synthase (FASN), a key enzyme in lipid biosynthesis, in the metabolic dysregulation of PCa. The Lu et al. study highlights HOXB13’s role in androgen receptor (AR)-independent PCa, where it regulates lipid metabolism via epigenetic mechanisms involving histone deacetylase HDAC3. A G84E mutation in HOXB13 disrupts this regulation, leading to increased lipid synthesis and a pro-metastatic phenotype. The Dairo et al. study demonstrates that FASN hypomethylation, coupled with increased expression, drives lipid biosynthesis critical for tumor growth. Both studies establish a link between HOXB13 mutations and FASN dysregulation, underscoring their interplay in PCa biology. Therapeutically, pharmacological inhibition of FASN mitigates the aggressive features of HOXB13-deficient or mutant PCa, highlighting lipid metabolism as a promising target. Despite their strengths, including robust methodologies, limitations include reliance on preclinical models and the need for broader patient diversity. These studies collectively emphasize the potential of metabolic and epigenetic interventions for precision medicine in PCa, paving the way for novel therapies targeting lipid metabolism in patients with specific genetic and epigenetic profiles.

The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer’s disease

Microglia are progressively activated by inflammation and exhibit phagocytic dysfunction in the pathogenesis of neurodegenerative diseases. Lipid-droplet-accumulating microglia were identified in the aging mouse and human brain; however, little is known about the formation and role of lipid droplets in microglial neuroinflammation of Alzheimer’s disease (AD). Here, we report a striking buildup of lipid droplets accumulation in microglia in the 3xTg mouse brain. Moreover, we observed significant upregulation of PKM2 and sterol regulatory element binding protein 1 (SREBP1) levels, which were predominantly localized in microglia of 3xTg mice. PKM2 dimerization was necessary for SREBP1 activation and lipogenesis of lipid droplet-accumulating microglia. RNA sequencing analysis of microglia isolated from 3xTg mice exhibited transcriptomic changes in lipid metabolism, innate inflammation, and phagocytosis dysfunction; these changes were improved with capsaicin-mediated pharmacological activation of TRPV1 via inhibition of PKM2 dimerization and reduction of SREBP1 activation. Lipid droplet-accumulating microglia exhibited increased mitochondrial injury accompanied by impaired mitophagy, which was abrogated upon of TRPV1 activation. Capsaicin also rescued neuronal loss, tau pathology, and memory impairment in 3xTg mice. Our study suggests that TRPV1-PKM2-SREBP1 axis regulation of microglia lipid metabolism could be a therapeutic approach to alleviate the consequences of AD.

Lipid metabolism and microbial regulation analyses provide insights into the energy-saving strategies of hibernating snakes

Hibernation is a necessary means for animals to maintain survival while coping with low temperatures and food shortages. While most studies have largely focused on mammalian hibernation, its reptilian equivalent has been less studied. In order to provide insights into the energy metabolism and potential microbial regulatory mechanisms in hibernating snakes, the serum, liver, gut content samples were measured by multi-omic methods. Here we show the active snakes have more vigorous lipid metabolism, whereas snakes in hibernation groups have higher sphingolipid metabolism. Furthermore, the results indicate that the potential energy supply pathway was gluconeogenesis. Microbial analysis reveals that Proteobacteria and Firmicutes showed dynamic changes with the transformation among active, pre-hibernation and hibernation periods. The correlation analysis reveals the potential role of Romboutsia, Providencia and Vagococcus in regulating above metabolism by producing certain metabolites. The results advance the understanding of the complex energy-saving strategy in hibernating poikilotherms.

The supply of branched-chain amino acids and branched-chain keto acids alter lipid metabolism, oxidative stress, and apoptosis in primary bovine hepatocytes.

Fatty liver impairs liver function and reduces productivity in dairy cows. Our previous in vivo findings demonstrated that branched-chain amino acids (BCAA) or branched-chain ketoacid (BCKA) improved liver function and lactation performance in dairy cows; however, the underlying mechanisms remain unclear. This study aimed to assess the impact of BCAA or BCKA supplementation on intracellular triglyceride (TG) accumulation, lipid metabolism, antioxidant response, and apoptosis in hepatocytes. Treatments were: control (CON): customized medium with amino acids, volatile fatty acids, fatty acids (FA), glucose, choline, insulin, and albumin concentrations equal to circulating levels in cows 4d postpartum; BCAA: CON + 33% additional BCAA of plasma BCAA 4d postpartum; and BCKA: CON + 33% additional BCKA of plasma BCAA 4d postpartum. Compared to CON, BCAA and BCKA reduced intracellular TG concentration by 32% and 40%, respectively, after 72 h. BCAA and BCKA enhanced the uptake of palmitic acid, but upregulated the expression of genes regulating FA oxidation. Although mitochondrial membrane potential was reduced, oxidative protein damage (protein carbonyl levels) was decreased in BCAA- and BCKA-treated hepatocytes without changes in mitochondrial copy number. Additionally, compared to CON, BCAA and BCKA decreased the expression of executioner caspases (caspase 3 and caspase 7) and reduced the portion of hepatocytes with activated caspase 3/7, suggesting reduced apoptosis. These findings suggest that BCAA or BCKA supplementation improves hepatocyte lipid metabolism, antioxidant defenses, and apoptosis regulation, potentially mitigating the adverse effects of fatty liver. These mechanisms likely underlie the previously observed improvements in liver function and lactation performance.

Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of Ceratonia siliqua and Ocimum basilicum Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study.

Hyperlipidemia is a serious risk factor for cardiovascular diseases and liver steatosis. In this work, we explored the effect of an herbal formula (CBF) containing immature Ceratonia siliqua pods and Ocimum basilicum extracts on lipid metabolism disorders and lipoprotein-rich plasma (LRP) oxidation in mice. The phenolic composition was determined using HPLC-DAD analysis. The antioxidant activity was studied using various in vitro methods. Acute toxicity was evaluated in mice. Importantly, the effect of the CBF on lipid metabolism disorders was investigated in a high-fat diet (HFD) hyperlipidemia mouse model. An in silico study was carried out to predict underlying mechanisms. The HPLC analysis revealed gallic acid, cinnamic acid, and naringenin as major phenolics of the carob pod aqueous extract. Concerning the basil hydro-ethanolic extract, rosmarinic, chicoric, caftaric, and caffeic acids were the main phenolics. Accordingly, the CBF prevented LRP oxidation in a concentration-dependent manner. This formula is not toxic in mice (LD50 > 2000 mg/kg body weight). Moreover, animals administered the CBF at 200 mg/kg/day presented a significant decline in their body weight gain, adipose tissue weight, plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C) level, and glycaemia after 10 weeks' treatment. Accordingly, the CBF decreased the plasma atherogenic index and the LDL-C to HDL-C ratio and reduced the level of fats accumulated in the liver. The molecular docking study revealed that chicoric, rosmarinic, and caftaric acids, and naringenin bound particularly strongly to many proteins involved in the regulation of lipid and cholesterol metabolism. This includes the HMG-CoA reductase, PPARα/γ, PCSK9, Cyp7a1, and ATP-citrate lyase. The CBF could be a good source of natural supplements, functional foods, and pharmaceuticals effective in managing hyperlipidemia and oxidative stress and preventing their related cardiovascular disorders.

Zhenwu Decoction Modulates PDE3A to Alleviate Inflammation in Diabetic Nephropathy

Background: Diabetic nephropathy, a complex microvascular complication of diabetes, poses substantial health and economic challenges globally. ZWD, known for its multi-component composition, has demonstrated potential therapeutic effects in DN, yet its molecular mechanisms require further elucidation to support its clinical application. Aim: This study aimed to comprehensively investigate the active components, target molecules, and molecular mechanisms of Zhenwu Decoction (ZWD), a Traditional Chinese Medicine (TCM) formula, in the treatment of diabetic nephropathy (DN), with a focus on its anti-inflammatory effects through the modulation of the PDE3A-mediated cAMP-PKA-NFκB axis. Objective: The primary objective was to identify the active components of ZWD, their targets, and the underlying molecular pathways through which ZWD exerts its therapeutic effects on DN, specifically focusing on the modulation of inflammation in renal cells under high glucose conditions. Method: A combined approach of network pharmacology, single-cell transcriptomics, and molecular docking analyses was employed to investigate the active components, target molecules, and underlying mechanisms of ZWD in treating DN. A high-glucose-induced HK-2 cell model was established to simulate in vitro DN conditions. Cell viability was assessed using the CCK-8 assay, while quantitative real-time PCR (qPCR) and Western blotting were employed to quantify gene expression and protein levels, respectively. Results: Our analysis uncovered 141 active components in ZWD, which targeted 171 proteins involved in pathways related to hypoxia response, neuroactive ligand-receptor interaction, urotensin II signaling, and other pathways implicated in diabetes and vascular diseases. Among these, 75 overlapping genes were pinpointed as potential therapeutic targets of ZWD for DN. Protein-protein interaction networks revealed three functional clusters of targets potentially associated with oxidative stress responses, lipid metabolism, and hormonal regulation. Cell-type specific analyses showed differential expression of these targets in DN, particularly in proximal tubular epithelial cells. Notably, through molecular docking, we discovered a strong binding affinity between PDE3A and betasitosterol. In vitro experiments confirmed that ZWD extract modulated PDE3A expression, leading to the suppression of the PKA/AMPK/NF-κB axis and attenuation of high glucose-induced inflammation in HK-2 cells. Conclusion: This study identified that Zhenwu Decoction (ZWD) suppressed high glucose-induced inflammation in renal cells by inhibiting the PDE3A-mediated cAMP-PKA-NFκB axis, highlighting the potential of ZWD as an effective adjunct therapy for diabetic nephropathy and paving the way for innovative anti-inflammatory treatments.

Progress in the Regulation of Lipid Metabolism by the Orphan Nuclear Receptor Nur77

Progress in the Regulation of Lipid Metabolism by the Orphan Nuclear Receptor Nur77

The therapeutic potential of apigenin against atherosclerosis.

Apigenin is a natural flavonoid abundantly found in fruits, vegetables, and medicinal plants. It possesses protective effects against cancer, metabolic syndrome, dyslipidemia, etc. Atherosclerosis, a chronic immune-mediated inflammatory disease, is the underlying cause of coronary heart disease, stroke, and myocardial infarction. Numerous in vivo and in vitro studies have shown a protective effect of apigenin against atherosclerosis, attributed to its antioxidant and anti-inflammatory properties, as well as its antihypertensive effect and regulation of lipid metabolism. This study aimed to review the effects and mechanisms of apigenin against atherosclerosis for the first time. Apigenin displays encouraging results, and this review confirms the potential value of apigenin as a candidate medication for atherosclerosis.