Lipid Metabolism Balance Research Articles

Ozone-Induced Lung Injury are Mediated Via PPAR-Mediated Ferroptosis in Mice.

In recent years, the concentration of PM2.5 in China has decreased, while the concentration of ozone remains rising. Exposure to ozone contributes to respiratory illnesses; however, little is known about the underlying molecular mechanisms. The present study established an ozone-induced lung injury mice model to investigate potential molecular biomarkers and toxic mechanisms. Collected and analyzed the ozone pollution data in Xinxiang city from 2015 to 2022. At the same time, 24 male C57BL/6 mice were randomly assigned to control group and ozone exposure group. The ozone exposure concentration is 1ppm, with 4h of daily exposure for 33 consecutive days. HE staining was used to assess lung histological alterations and lung injury. High-throughput sequencing performed on the lung tissues of mice was used to analyze the differential expressed genes and signal transduction pathways. Xinxiang city is suffering from ozone pollution, especially in summer. HE staining showed that the ozone exposure could induce obvious inflammatory cell infiltration, alveolar wall thickening, or fracture. Transcriptome data revealed that there is a 145 differentially expressed genes between two groups and the genes enriched in PPAR signaling pathway, ferroptosis. The pivotal genes in the PPAR pathway including Adipoq, Lpl, Pck1, and Plin1 expression were significantly reduced. Additionally, the expression of Acsl6 and Scl7a11, which are close to PPAR pathway and ferroptosis has decreased. Ozone exposure could disrupt the lipid metabolism balance via downregulating lipid peroxidation-related genes through the PPAR signaling pathway, which further induced lung cell ferroptosis and aggravated lung injury in mice.

Stilbene glycosides alleviate atherosclerosis partly by promoting lipophagy of dendritic cells

Atherosclerosis (AS) is a chronic inflammatory disease resulting from lipid metabolism disorders and immune imbalances. Dendritic cells (DCs) are key cells that regulate adaptive and adaptive immunity. When DCs engulf excessive amounts lipids, their function is altered, thereby, accelerating the inflammatory process of AS. Cellular lipophagy serves to reduce lipid accumulation and maintain cellular lipid metabolism balance. In this study, we investigated the effectiveness of 2,3,5,4′-tetrahydroxystilbene 2-O-β-D-glucoside (TSG) in intervening in the promotion of DCs lipid accumulation by ox-LDL, as well as its role in downregulating lipophagy. Our findings indicate that TSG reduces the maturity of DCs and promotes the differentiation of T cells towards Treg, thereby correcting the imbalanced Treg/Th17. These effects of TSG are closely associated with its inhibition of the PI3K-AKT-mTOR signaling pathway. After administering TSG to ApoE-/- mice that were fed a high-fat diet, there was a noticeable decrease in harmful blood lipids found in the serum. Additionally, the imbalanced Treg/Th17 levels in the spleen were restored, and the levels of pro-inflammatory factor IL-6 and IL-17A in the serum decreased, while the level of anti-inflammatory factor IL-10 increased. Furthermore, the arterial DCs showed a decrease in P62 content. Ultimately, these changes resulted in a reduction in plaque area. It is worth noting that the autophagy inhibitor chloroquine significantly altered the effects of TSG on ApoE-/- mice. In conclusion, this study reveals that TSG can alleviate AS. This is partly achieved through the activation of autophagy in DCs. By intervening in the lipophagy of DCs, it is possible to regulate the immune function of these cells, which in turn helps control the inflammation associated with AS. This presents a potential method for intervening in AS.

Effects of low temperature air exposure and immersion on antioxidant, immune, intestinal flora and metabolome of Chinese mitten crab (Eriocheir sinensis)

The aim of this study was to investigate the effects of immersion on immune enzyme activity, haemolymph index, intestinal microbiome and metabolome of E. sinensis after low temperature air exposure. The results showed that low temperature air exposure induced stress response, which led to hepatopancreas injury and increased membrane permeability, but this situation was reversible and alleviated after immersion. In addition, after exposure to low temperature air, haemolymph metabolism-related substances such as glucose and total cholesterol were significantly different from the initial value (P < 0.05), and gradually returned to the initial level after immersion. The changes of intestinal flora and hepatopancreas metabolism caused by low temperature air exposure did not fully recover after immersion, and its negative effects did not completely disappear. The sequencing results showed that the species composition and diversity of intestinal microorganisms of Chinese mitten crabs were changed after low temperature air exposure and immersion treatment. The relative abundance of Bacteroidetes and Proteobacteria were increased, while the relative abundance of Firmicutes was decreased (P < 0.05). Metabolomics analysis showed that lysine levels increased significantly, taurocholic acid levels decreased significantly, and amino acid metabolism and lipid metabolism balance were disturbed in hepatopancreas of E. sinensis after exposure to low temperature air and immersion (P < 0.05). This study will provide new insights into the recovery mechanism of water immersion on Chinese mitten crabs after exposure to air.

Vitamin D3 alleviates the damage caused by high-fat and maintains lipid metabolism homeostasis in hepatopancreas by promoting fatty acid β-oxidation of Portunus trituberculatus

The purpose of present study was to evaluate the effects of vitamin D3 supplementation in high-fat diet on growth performance, calcium and phosphorus in tissue, immunity and lipid metabolism, and to explore whether adding vitamin D3 to high-fat diet can alleviate the adverse effects of high-fat diet on swimming crab (Portunus trituberculatus). The three experimental diets were normal fat diet (NFD, 9.35 % fat, 45.53 % protein), high fat diet (HFD, 14.69 % fat, 44.93 % protein) and high fat diet supplemented with 0.47 mg/kg VD3 (HFD+VD), respectively. A total of 108 healthy swimming crabs with an initial body weight of 9.42±0.13 g were selected for an 8-week feeding trial. The results showed that crabs fed with HFD+VD diet exhibited significantly higher percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE) and molting rate (MR) compared to those fed with HFD diet (P < 0.05). It was observed from hepatopancreas crude lipid content, TG content and hepatopancreas sections that HFD caused hepatopancreatic cell damage and abnormal lipid accumulation (P < 0.05), however, there were no significant differences in hepatopancreas crude fat content, TG content and hepatopancreas section observation between HFD+VD group and NFD group (P > 0.05). Crabs fed HFD diets with or without VD3 significantly down-regulated the expression of genes related to fatty acid transport, such as fabp9 and lpr1 in hepatopancreas (P < 0.05), moreover, the expression of genes related to fatty acid β-oxidation (cpt2 and acox1) were significantly up-regulated and genes related to lipid synthesis (fas and 6pgd) were significantly down-regulated in the hepatopancreas of the crabs fed with HFD+VD diet compared to those fed with HFD diet (P < 0.05). In conclusion, the results of present study indicated that a high-fat diet can cause deformation and rupture of hepatopancreas cells through abnormal lipid accumulation, thereby causing associated inflammation, leading to large calcium and phosphorus deposits in hemolymph and muscle, however, high fat diet supplemented with vitamin VD3 mainly enhanced the β-oxidation of fatty acids, inhibited lipid synthesis, alleviated abnormal lipid accumulation, and thus maintained the balance of lipid metabolism in hepatopancreas cells and promoted growth performance and feed utilization for swimming crab.

Unbalanced lipid metabolism in anther, especially the disorder of the alpha-linolenic acid metabolism pathway, leads to cotton male sterility

Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility. However, how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear. Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility. In this study, we compared the transcriptome and the composition and content of lipids in anthers of two Upland cotton (Gossypium hirsutum) materials, Shida 98 (WT) and its nearly-isogenic male sterile line Shida 98A (MS). Transcriptomics analysis identified many differentially expressed genes between the two materials, with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype. Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids (FFAs), phosphatidic acid (PA), mono- and di-galactosyldiacylglycerol (MGDG and DGDG), and had a decreased content of triacylglycerol (TAG), which was closely related to the abnormal metabolism of alpha-linolenic acid (C18:3); therefore, the major lipids containing C18:3-acyl chains, such as PA, MGDG, DGDG and TAG, are proposed to play a major role in cotton anther development. We also showed that an excessive level of MGDG and DGDG caused JA overaccumulation in MS anthers, which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content, presumably via a feedback regulation mechanism, ultimately affecting plant fertility. Together, our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.

Soy Peptide Supplementation Mitigates Undernutrition through Reprogramming Hepatic Metabolism in a Novel Undernourished Non-Human Primate Model.

In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human-relevant criterion for determining undernutrition weight-for-age z-score (WAZ), with a cutoff point of ≤ -1.83 is established as the benchmark for identifying undernourished nonhuman primates (U-NHPs). In U-NHPs, pathological anomalies in multi-organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U-NHPs. Mitochondria dysfunction is typified by reduced mito-number, accumulated long-chain fatty acids, and disruption of OXPHOS complexes. Soy peptide-treated U-NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U-NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re-establish lipid metabolism balance and mitigated undernutrition.

A Novel Tetrapeptide Ala-Phe-Phe-Pro (AFFP) Derived from Antarctic Krill Prevents Scopolamine-Induced Memory Disorder by Balancing Lipid Metabolism of Mice Hippocampus.

Memory impairment is a serious problem with organismal aging and increased social pressure. The tetrapeptide Ala-Phe-Phe-Pro (AFFP) is a synthetic analogue of Antarctic krill derived from the memory-improving Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) after digestion and absorption. The objective of this research was to assess the neuroprotective effects of AFFP by reducing oxidative stress and controlling lipid metabolism in the brains of mice with memory impairment caused by scopolamine. The 1H Nuclear magnetic resonance spectroscopy results showed that AFFP had three active hydrogen sites that could contribute to its antioxidant properties. The findings from in vivo tests demonstrated that AFFP greatly enhanced the mice's behavioral performance in the passive avoidance, novel object recognition, and eight-arm maze experiments. AFFP reduced oxidative stress by enhancing superoxide dismutase activity and malondialdehyde levels in mice serum, thereby decreasing reactive oxygen species level in the mice hippocampus. In addition, AFFP increased the unsaturated lipid content to balance the unsaturated lipid level against the neurotoxicity of the mice hippocampus. Our findings suggest that AFFP emerges as a potential dietary intervention for the prevention of memory impairment disorders.

Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway

Ethnopharmacological relevanceGlobally, the incidence rate and number of patients with nonalcoholic fatty liver disease are increasing, which has become one of the greatest threats to human health. However, there is still no effective therapy and medicine so far. Silphium perfoliatum L. is a perennial herb native to North America, which is used to improve physical fitness and treat liver and spleen related diseases in the traditional medicinal herbs of Indian tribes. This herb is rich in chlorogenic acids, which have the functions of reducing blood lipids, losing weight and protecting liver. However, the effect of these compounds on nonalcoholic fatty liver disease remains unclear. Aim of the studyClarify the therapeutic effects and mechanism of the extract (CY-10) rich in chlorogenic acid and its analogues from Silphium perfoliatum L. on non-alcoholic fatty liver disease, and to determine the active compounds. Materials and methodsA free fatty acid-induced steatosis model of HepG2 cells was established to evaluate the in vitro activity of CY-10 in promoting lipid metabolism. Further, a high-fat diet-induced NAFLD model in C57BL/6 mice was established to detect the effects of CY-10 on various physiological and biochemical indexes in mice, and to elucidate the in vivo effects of the extract on regulating lipid metabolism, anti-inflammation and hepatoprotection, and nontarget lipid metabolomics was performed to analyze differential metabolites of fatty acids in the liver. Subsequently, western blotting and immunohistochemistry were used to analyze the target of the extract and elucidate its mechanism of action. Finally, the active compounds in CY-10 were elucidated through in vitro activity screening. ResultsThe results indicated that CY-10 significantly attenuated lipid droplet deposition in HepG2 cells. The results of in vivo experiments showed that CY-10 significantly reduce HFD-induced mouse body weight and organ index, improve biochemical indexes, oxidation levels and inflammatory responses in the liver and serum, thereby protecting the liver tissue. It can promote the metabolism of unsaturated fatty acids in the liver and reduce the generation of saturated fatty acids. Furthermore, it is clarified that CY-10 can promote lipid metabolism balance by regulating AMPK/FXR/SREPB-1c/PPAR-γ signal pathway. Ultimately, the main active compound was proved to be cryptochlorogenic acid, which has a strong promoting effect on the metabolism of fatty acids in cells. Impressively, the activities of CY-10 and cryptochlorogenic acid were stronger than simvastatin in vitro and in vivo. ConclusionFor the first time, it is clarified that the extract rich in chlorogenic acids and its analogues in Silphium perfoliatum L. have good therapeutic effects on non-alcoholic fatty liver disease. It is confirmed that cryptochlorogenic acid is the main active compound and has good potential for medicine.

A multiscale modeling study of nanoparticle-based targeting therapy against atherosclerosis

Although researches on nanoparticle-based (NP-based) drug delivery system for atherosclerosis treatment have grown rapidly in recent years, there are limited studies in quantifying the effects of targeting drugs on plaque components and microenvironment. The purpose of the present study was to quantitatively assess the targeting therapeutic effects against atherosclerosis by establishing a multiscale mathematical model.The multiscale model involved subcellular, cellular and microenvironmental scales to simulate lipid catabolism, macrophage behaviors and dynamics of microenvironmental components, respectively. In vitro and in vivo experimental data were integrated into the mathematical model according to Bayesian statistics, in order to evaluate the therapeutic effects of a proposed NP-based platform for macrophage-specific delivery to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR-L (to stimulate cholesterol efflux). Dosage variation analysis was then performed to investigate the drug efficacy under varied dosage combinations of SR-A siRNA and LXR-L.The simulation results demonstrated that the dynamics of the microenvironmental components presented different developments in Untreated and Treated groups. We also found that the balance of lipid metabolism between uptake and efflux resulted in the improvement of lipid and inflammatory microenvironment, consequently in the plaque regression. In addition, the model predicted optimized dosage combinations according to the co-effect analysis of the two drugs on the lipid microenvironment.This study suggests that multiscale modeling can be a powerful quantitative tool for estimating the therapeutic effects of targeting drugs for plaque regression and designing the enhanced treatment strategies against atherosclerosis.

The neuroprotective effects of SFGDI on sirtuin 3-related oxidative stress by regulating the Sirt3/SOD/ROS pathway and energy metabolism in BV2 cells.

Recently, the investigation of neuroprotective peptides has gained attention in addressing memory impairment and cognitive decline. Although the potential neuroprotective peptide Serine-Phenylalanine-Glycine-Aspartic acid-Isoleucine (SFGDI) has been identified from sea cucumber, the molecular mechanisms remain unclear. This study was conducted to explore the neuroprotection of SFGDI against 3-TYP-induced oxidative stress in BV2 cells. The results showed a retention rate of 76.70% during in vitro simulated gastrointestinal digestion and an absorption rate of 10.41% in a rat-everted gut sac model for SFGDI. Two hours following the administration of SFGDI via gavage in mice, a notable fluorescence was observed in the brain, indicating a potential neuroprotection of SFGDI through its interactions with nerve cells. By utilizing a model of oxidative stress injury induced by 3-TYP in BV2 cells, it was determined that pretreatment with SFGDI (50-200 μg mL-1) resulted in a dose-dependent reduction in the acetylated SOD level, leading to enhanced SOD activity and reduced levels of ROS and MDA. In addition, this pretreatment triggered an increase in unsaturated lipid levels, which helped maintain the intracellular lipid metabolism balance and preserve the mitochondrial function and glycolysis levels to regulate energy metabolism. The results of this study indicate that SFGDI demonstrates neuroprotective properties through its modulation of the Sirt3/SOD/ROS pathway, regulation of lipid metabolism, and enhancement of energy metabolism in BV2 cells. These findings suggest potential novel therapeutic approaches for addressing Sirt3-related memory deficits and neurodegenerative disorders.

Glucokinase regulatory protein: a balancing act between glucose and lipid metabolism in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide, affected by both genetics and environment. Type 2 diabetes (T2D) stands as an independent environmental risk factor that precipitates the onset of hepatic steatosis and accelerates its progression to severe stages of liver damage. Furthermore, the coexistence of T2D and NAFLD magnifies the risk of cardiovascular disease synergistically. However, the association between genetic susceptibility and metabolic risk factors in NAFLD remains incompletely understood. The glucokinase regulator gene (GCKR), responsible for encoding the glucokinase regulatory protein (GKRP), acts as a regulator and protector of the glucose-metabolizing enzyme glucokinase (GK) in the liver. Two common variants (rs1260326 and rs780094) within the GCKR gene have been associated with a lower risk for T2D but a higher risk for NAFLD. Recent studies underscore that T2D presence significantly amplifies the effect of the GCKR gene, thereby increasing the risk of NASH and fibrosis in NAFLD patients. In this review, we focus on the critical roles of GKRP in T2D and NAFLD, drawing upon insights from genetic and biological studies. Notably, prior attempts at drug development targeting GK with glucokinase activators (GKAs) have shown potential risks of augmented plasma triglycerides or NAFLD. Conversely, overexpression of GKRP in diabetic rats improved glucose tolerance without causing NAFLD, suggesting the crucial regulatory role of GKRP in maintaining hepatic glucose and lipid metabolism balance. Collectively, this review sheds new light on the complex interaction between genes and environment in NAFLD, focusing on the GCKR gene. By integrating evidence from genetics, biology, and drug development, we reassess the therapeutic potential of targeting GK or GKRP for metabolic disease treatment. Emerging evidence suggests that selectively activating GK or enhancing GK-GKRP binding may represent a holistic strategy for restoring glucose and lipid metabolic balance.

Tryptophan metabolite norharman secreted by cultivated Lactobacillus attenuates acute pancreatitis as an antagonist of histone deacetylases

BackgroundPatients with acute pancreatitis (AP) exhibit specific phenotypes of gut microbiota associated with severity. Gut microbiota and host interact primarily through metabolites; regrettably, little is known about their roles in AP biological networks. This study examines how enterobacterial metabolites modulate the innate immune system in AP aggravation.MethodsIn AP, alterations in gut microbiota were detected via microbiomics, and the Lactobacillus metabolites of tryptophan were identified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). By culturing Lactobacillus with tryptophan, differential metabolites were detected by LC–MS/MS. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice with cerulein plus LPS-induced AP were used to evaluate the biological effect of norharman on M1 macrophages activation in AP development. Further, RNA sequencing and lipid metabolomics were used for screening the therapeutic targets and pathways of norharman. Confocal microscopy assay was used to detect the structure of lipid rafts. Molecular docking was applied to predict the interaction between norharman and HDACs. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to explore the direct mechanism of norharman promoting Rftn1 expression. In addition, myeloid-specific Rftn1 knockout mice were used to verify the role of Rftn1 and the reversed effect of norharman.ResultsAP induced the dysfunction of gut microbiota and their metabolites, resulting in the suppression of Lactobacillus-mediated tryptophan metabolism pathway. The Lactobacillus metabolites of tryptophan, norharman, inhibited the release of inflammatory factor in vitro and in vivo, as a result of its optimal inhibitory action on M1 macrophages. Moreover, norharman blocked multiple inflammatory responses in AP exacerbation due to its ability to maintain the integrity of lipid rafts and restore the dysfunction of lipid metabolism. The mechanism of norharman’s activity involved inhibiting the enzyme activity of histone deacetylase (HDACs) to increase histone H3 at lysine 9/14 (H3K9/14) acetylation, which increased the transcription level of Rftn1 (Raftlin 1) to inhibit M1 macrophages’ activation.ConclusionsThe enterobacterial metabolite norharman can decrease HDACs activity to increase H3K9/14 acetylation of Rftn1, which inhibits M1 macrophage activation and restores the balance of lipid metabolism to relieve multiple inflammatory responses. Therefore, norharman may be a promising prodrug to block AP aggravation.Graphical

A Study on the Amelioration of Circadian Rhythm Disorders in Fat Mice Using High-Protein Diets.

This innovative study investigates the effects of high-protein diets (milk protein) on the circadian rhythm of hepatic lipid metabolism. We aimed to understand how high-protein interventions regulate biological clock genes, maintain lipid metabolism balance, and affect the circadian rhythm of antioxidant levels in vivo. We divided 120 SPF-class C57BL/6J mice into the control, high-fat/low-protein (HF-LP), and high-fat/high-protein (HF-HP) groups. Mice were sacrificed during active (2 a.m. and 8 a.m.) and rest periods (2 p.m. and 8 p.m.). In the HF-LP group, hepatic lipid anabolic enzymes were consistently expressed at high levels, while key lipolytic enzymes slowly increased after feeding with no significant diurnal differences. This led to an abnormal elevation in blood lipid levels, a slow increase in and low levels of superoxide dismutase, and a rapid increase in malondialdehyde levels, deviating from the diurnal trend observed in the control group. However, high-protein interventions in the HF-HP group restored lipid synthase activity and the expression of key catabolic enzymes, exhibiting a precise circadian rhythm. It also improved the lipid-metabolism rhythm, which was disrupted by the high-fat diet. Overall, high-protein interventions restored the expression of key enzymes involved in lipid metabolism, improving the lipid-metabolism rhythm, which was disrupted by the high-fat diet.

IRE1α: from the function to the potential therapeutic target in atherosclerosis.

Inositol requiring enzyme 1 (IRE1) is generally thought to control the most conserved pathway in the unfolded protein response (UPR). Two isoforms of IRE1, IRE1α and IRE1β, have been reported in mammals. IRE1α is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1β is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1β-knockout mice are phenotypically normal. As research continues to deepen, IRE1α was showed to be tightly linked to inflammation, lipid metabolism regulation, cell death and so on. Growing evidence also suggests an important role for IRE1α in promoting atherosclerosis (AS) progression and acute cardiovascular events through disrupting lipid metabolism balance, facilitating cells apoptosis, accelerating inflammatory responses and promoting foam cell formation. In addition, IRE1α was recognized as novel potential therapeutic target in AS prevention. This review provides some clues about the relationship between IRE1α and AS, hoping to contribute to further understanding roles of IRE1α in atherogenesis and to be helpful for the design of novel efficacious therapeutics agents targeting IRE1α-related pathways.

Research progress on the mitochondrial mechanism of age-related non-alcoholic fatty liver.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Reduced activity and slower metabolism in the elderly affect the balance of lipid metabolism in the liver leading to the accumulation of lipids. This affects the mitochondrial respiratory chain and the efficiency of β-oxidation and induces the overproduction of reactive oxygen species. In addition, the dynamic balance of the mitochondria is disrupted during the ageing process, which inhibits its phagocytic function and further aggravates liver injury, leading to a higher incidence of NAFLD in the elderly population. The present study reviewed the manifestations, role and mechanism of mitochondrial dysfunction in the progression of NAFLD in the elderly. Based on the understanding of mitochondrial dysfunction and abnormal lipid metabolism, this study discusses the treatment strategies and the potential therapeutic targets for NAFLD, including lipid accumulation, antioxidation, mitophagy and liver-protecting drugs. The purpose is to provide new ideas for the development of innovative drugs for the prevention and treatment of NAFLD.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism

Studies have shown that a high-fat diet (HFD) can alter gut microbiota (GM) homeostasis and participate in lipid metabolism disorders associated with obesity. Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract (Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases. To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism. Obesity was induced in rats with an HFD for 7 wk, and Sal (0.675 g/1.35 g/2.70 g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors (cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNA-based microbiota analysis and untargeted lipidomic analysis (LC-MS/MS), respectively. Sal treatment markedly reduced weight, body fat index, serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein (HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as cAMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs (TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs (DG14:0/22:6, DG22:6/22:6), CL (18:2/ 18:1/18:1/20:0), and increased ceramides (Cers; Cer d16:0/21:0, Cer d16:1/24:1), (O-acyl)-ω-hydroxy fatty acids (OAHFAs; OAHFA18:0/14:0) in the feces of rats. Spearman's correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite. Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

Modulatory Effect of Limosilactobacillus fermentum grx08 on the Anti-Oxidative Stress Capacity of Liver, Heart, and Kidney in High-Fat Diet Rats

To explore the modulating effect of Limosilactobacillus fermentum (L. fermentum) grx08 on anti-oxidative stress in the liver, heart, and kidney of high-fat diet in rats, a low-fat diet as a control and a high-fat diet was used to induce oxidative stress injury in rats. L. fermentum grx08 and its heat-inactivated bacteria were used to intervene. The results showed that the high-fat diet had caused oxidative stress injury in the liver, heart, and kidney of rats. L. fermentum grx08 significantly reduced the serum levels of liver, heart, and kidney injury markers (ALT, AST, LDH, CK-MB, UA, and Crea), while restoring the balance of lipid metabolism in the liver. It also enhanced the activity of antioxidant enzymes such as GSH-Px in the liver, heart, and kidney, scavenging NO radicals and reducing the content of MDA, a product of lipid peroxidation, which can regulate the anti-oxidative stress capacity of the liver, heart, and kidney to varying degrees. Among them, L. fermentum grx08 showed better modulating effect on kidney anti-oxidative stress, followed by liver, and the weakest modulating effect on heart. At the same time, L. fermentum grx08 heat-inactivated bacteria also had a partial modulatory effect as well as a similar effect profile to that of live bacteria.

Lactobacillus rhamnosus Hsryfm 1301 Fermented Milk Regulates Lipid Metabolism and Inflammatory Response in High-Fat Diet Rats

A rat model of disordered lipid metabolism was established to study the regulation of lipid metabolism and inflammatory response by Lactobacillus rhamnosus hsryfm 1301 fermented milk. The results showed that the high-fat diet caused the disorder of lipid metabolism in rats, accompanied by the occurrence of an inflammatory response. After Lactobacillus rhamnosus hsryfm 1301 fermented milk intervention, the blood lipid level was reduced along with the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as triglyceride (TG) and total cholesterol (TC) contents in the liver of rats (p &lt; 0.05), the fat vacuoles of rat hepatocytes were reduced, and the lipid accumulation in the rat liver was decreased. Liver injury was restored. Meanwhile, the levels of free fatty acid (FFA) and fatty acid synthase (FAS), acetyl coenzyme A carboxylase (ACC), lipoprotein esterase (LPL) and hepatic lipase (HL) in serum and liver of rats were significantly lower than those in the model group (p &lt; 0.05), which indicated that fatty acid synthesis was inhibited, fatty acid production was reduced and lipid metabolism was restored to balance. In addition, the levels of reactive oxygen species (ROS) and inflammatory factors in the serum of rats were also significantly reduced (p &lt; 0.05), and the inflammatory response of rats was restored. Lactobacillus rhamnosus hsryfm 1301 fermented milk could not only inhibit fatty acid synthase but reduce the production of excessive fatty acids, thus reducing fat accumulation, restoring the balance of lipid metabolism and alleviating the inflammatory response in rats. At the same time, it can also reduce the level of ROS through the antioxidant effect, alleviate the inflammatory response, and thus alleviate the disorder of lipid metabolism.

Litchi flower essential oil balanced lipid metabolism through the regulation of DAF-2/IIS, MDT-15/SBP-1, and MDT-15/NHR-49 pathway.

Many litchi flowers are discarded in China every year. The litchi flower is rich in volatile compounds and exhibits strong anti-obesity activity. Litchi flower essential oil (LFEO) was extracted by the continuous phase transformation device (CPTD) independently developed by our research group to recycle the precious material resources in litchi flowers. However, its fat-reducing effect and mechanism remain unclear. Employing Caenorhabditis elegans as a model, we found that LFEO significantly reduced fat storage and triglyceride (TG) content in normal, glucose-feeding, and high-fat conditions. LFEO significantly reduced body width in worms and significantly decreased both the size and number of lipid droplets in ZXW618. LFEO treatment did not affect energy intake but increased energy consumption by enhancing the average speed of worms. Further, LFEO might balance the fat metabolism in worms by regulating the DAF-2/IIS, sbp-1/mdt-15, and nhr-49/mdt-15 pathways. Moreover, LFEO might inhibit the expression of the acs-2 gene through nhr-49 and reduce β-oxidation activity. Our study presents new insights into the role of LFEO in alleviating fat accumulation and provides references for the large-scale production of LFEO to promote the development of the litchi circular economy.

Inhibition of inflammasome activation via sphingolipid pathway in acute lung injury by Huanglian Jiedu decoction: An integrative pharmacology approach

BackgroundAcute lung injury (ALI) is a serious health issue which causes significant morbidity and mortality. Inflammation is an important factor in the pathogenesis of ALI. Even though ALI has been successfully managed using a traditiomal Chinese medicine (TCM), Huanglian Jiedu Decoction (HLD), its mechanism of action remains unknown. PurposeThis study explored the therapeutic potential of HLD in lipopolysaccharide (LPS)-induced ALI rats by utilizing integrative pharmacology. MethodsHere, the therapeutic efficacy of HLD was evaluated using lung wet/dry weight ratio (W/D), myeloperoxide (MPO) activity, and levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6. Network pharmacology predictd the active components of HLD in ALI. Lung tissues were subjected to perform Hematoxylin-eosin (H&E) staining, metabolomics, and transcriptomics. The acid ceramidase (ASAH1) inhibitor, carmofur, was employedto suppress the sphingolipid signaling pathway. ResultsHLD reduced pulmonary edema and vascular permeability, and suppressed the levels of TNF-α, IL-6, and IL-1β in lung tissue, Bronchoalveolar lavage fluid (BALF), and serum. Network pharmacology combined with transcriptomics and metabolomics showed that sphingolipid signaling was the main regulatory pathway for HLD to ameliorate ALI, as confirmed by immunohistochemical analysis. Then, we reverse verified that the sphingolipid signaling pathway was the main pathway involed in ALI. Finally, berberine, baicalein, obacunone, and geniposide were docked with acid ceramidase to further explore the mechanisms of interaction between the compound and protein. ConclusionHLD does have a better therapeutic effect on ALI, and its molecular mechanism is better elucidated from the whole, which is to balance lipid metabolism, energy metabolism and amino acid metabolism, and inhibit NLRP3 inflammasome activation by regulating the sphingolipid pathway. Therefore, HLD and its active components can be used to develop new therapies for ALI and provide a new model for exploring complex TCM systems for treating ALI.