Regulating Glycolipid Metabolism Research Articles

The Beneficial Effect of a Healthy Dietary Pattern on Androgen Deprivation Therapy-Related Metabolic Abnormalities in Patients with Prostate Cancer: A Meta-Analysis Based on Randomized Controlled Trials and Systematic Review.

Metabolic abnormalities as side effects of androgen-deprivation therapy (ADT) can accelerate progression of prostate cancer (PCa) and increase risks of cardiovascular diseases. A healthy dietary pattern (DP) plays an important role in regulating glycolipid metabolism, while evidence about DP on ADT-related metabolic abnormalities is still controversial. To explore the effect of DP on metabolic outcomes in PCa patients with ADT, PubMed, Embase, Cochrane, and CINAHL were searched from inception to 10 September 2022. Risk of biases was evaluated through Cochrane Collaboration’s Tool. If heterogeneity was low, the fixed-effects model was carried out; otherwise, the random-effects model was used. Data were determined by calculating mean difference (MD) or standardized MD (SMD) with 95% confidence intervals (CIs). Nine studies involving 421 patients were included. The results showed that healthy DP significantly improved glycated hemoglobin (MD: −0.13; 95% CI: −0.24, −0.02; p = 0.020), body mass index (MD: −1.02; 95% CI: −1.29, −0.75; p < 0.001), body fat mass (MD: −1.78; 95% CI: −2.58, −0.97; p < 0.001), triglyceride (MD: −0.28; 95% CI: −0.51, −0.04; p = 0.020), systolic blood pressure (MD: −6.30; 95% CI: −11.15, −1.44; p = 0.010), and diastolic blood pressure (MD: −2.94; 95% CI: −5.63, −0.25; p = 0.030), although its beneficial effects on other glycolipid metabolic indicators were not found. Additionally, a healthy DP also lowered the level of PSA (MD: −1.79; 95% CI: −2.25, −1.33; p < 0.001). The meta-analysis demonstrated that a healthy DP could improve ADT-related metabolic abnormalities and be worthy of being recommended for PCa patients with ADT.

Glucagon-like peptide-1 receptor mediates the improvement in glycolipid metabolism disorder via AKT and AMPK signalling pathways in L02 cells with insulin resistance

Glucagon-like peptide 1 (GLP-1) has previously been found to regulate glycolipid metabolism in the liver by promoting insulin secretion. However, the presence of GLP-1 receptors (GLP-1R) in the human liver has not been determined. In this research, GLP-1R was found to be expressed in L02 cells and decreased in insulin resistant (IR) cells. Compared with LG treatment group, GLP-1R knockdown significantly decreased glucose utilization (from 143.13% to 118.41%.) and intracellular glycogen content (from 122.77% to 105.72%). Furthermore, the transcription levels of PEPCK and G6Pase increased, and the phosphorylation levels of AKT, FOXO1 and GSK3β decreased in siGLP-1R group. Similarly, the contents of triglyceride and total cholesterol in siGLP-1R group increased by 43.23% and 24.19%, respectively. PCR and WB results showed that knockdown of GLP-1R increased the levels of ACC, FAS, and SREBP-1c, and decreased the levels of CPT-1 via AMPK pathway. GLP-1R knockdown changed the LG-induced promotion of glucose utilization and inhibition of lipid synthesis. These findings demonstrated that GLP-1R is the molecular basis for GLP-1 to improve glycolipid metabolism in L02 cells.

Nao Tan Qing ameliorates Alzheimer's disease-like pathology by regulating glycolipid metabolism and neuroinflammation: A network pharmacology analysis and biological validation

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and currently there are no available treatments. Alongside the conventional Aβ and tau hypotheses, neuroinflammation and metabolism disruption have also been regarded as crucial hallmarks of AD. In this study, a novel Chinese formula Nao Tan Qing (NTQ) was developed and shown to improve AD. In vivo experiments showed that NTQ significantly mitigated cognitive impairment, Aβ burden and neuroinflammation in a transgenic AD mouse model (5×FAD). Network pharmacology results revealed that the active components of NTQ could target inflammatory and metabolic pathways. In addition, hippocampal transcriptomics suggested that NTQ regulated signaling pathways related to inflammation and lipid metabolism. Consistently, serum metabolomics further indicated that NTQ could modulate glycolipid metabolism. In summary, a combination of systems pharmacology analysis and biological validation study demonstrates that NTQ could alleviate behavioral abnormality and pathological alterations of AD by targeting glycolipid metabolism and neuroinflammation, and is accordingly a potential therapeutic agent for AD.

The new exploration of pure total flavonoids extracted from Citrus maxima (Burm.) Merr. as a new therapeutic agent to bring health benefits for people.

The peel and fruit of Citrus varieties have been a raw material for some traditional Chinese medicine (TCM). Pure total flavonoids from Citrus maxima (Burm.) Merr. (PTFC), including naringin, hesperidin, narirutin, and neohesperidin, have been attracted increasing attention for their multiple clinical efficacies. Based on existing in vitro and in vivo research, this study systematically reviewed the biological functions of PTFC and its components in preventing or treating liver metabolic diseases, cardiovascular diseases, intestinal barrier dysfunction, as well as malignancies. PTFC and its components are capable of regulating glycolipid metabolism, blocking peroxidation and persistent inflammation, inhibiting tumor progression, protecting the integrity of intestinal barrier and positively regulating intestinal microbiota, while the differences in fruit cultivation system, picking standard, manufacturing methods, delivery system and individual intestinal microecology will have impact on the specific therapeutic effect. Thus, PTFC is a promising drug for the treatment of some chronic diseases, as well as continuous elaborate investigations are necessary to improve its effectiveness and bioavailability.

Bifidobacterium longum 070103 Fermented Milk Improve Glucose and Lipid Metabolism Disorders by Regulating Gut Microbiota in Mice.

Background: Fermented milk is beneficial for metabolic disorders, while the underlying mechanisms of action remain unclear. This study explored the benefits and underlying mechanisms of Bifidobacterium longum 070103 fermented milk (BLFM) in thirteen-week high-fat and high-sugar (HFHS) fed mice using omics techniques. Methods and results: BLFM with activated glucokinase (GK) was screened by a double-enzyme coupling method. After supplementing BLFM with 10 mL/kg BW per day, fasting blood glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and leptin were significantly reduced compared with the HFHS group. Among them, the final body weight (BW), epididymal fat, perirenal fat, and brown fat in BLFM group had better change trends than Lacticaseibacillus rhamnosus GG fermented milk (LGGFM) group. The amplicon and metabolomic data analysis identified Bifibacterium as a key gut microbiota at regulating glycolipid metabolism. BLFM reverses HFHS-induced reduction in bifidobacteria abundance. Further studies showed that BLFM significantly reduces the content of 3-indoxyl sulofphate associated with intestinal barrier damage. In addition, mice treated with BLFM improved BW, glucose tolerance, insulin resistance, and hepatic steatosis. Conclusion: BLFM consumption attenuates obesity and related symptoms in HFHS-fed mice probably via the modulation of gut microbes and metabolites.

Structural Characteristics and the Antioxidant and Hypoglycemic Activities of a Polysaccharide from Lonicera caerulea L. Pomace

In this study, a novel polysaccharide, LPP, was obtained from Lonicera caerulea L. pomace by ultrasonic-assisted heating and was purified by Sephadex G-100. The structural characteristics of LPP showed that the molecular weight (Mw) was 8.53 × 104 Da; that it was mainly composed of galacturonic acid, followed by galactose; that it possessed the characteristic functional groups of polysaccharides; and that it had an absence of O-glycosidic bonds and crystalline and triple helix structures. Furthermore, LPP exhibited a favorable thermodynamic stability and antioxidant, hypoglycemic, and hypolipidemic activities in a dose-dependent manner in vitro, demonstrating that LPP can be used as an agent to regulate glycolipid metabolism. Additionally, the relationship between its bio-activities is discussed in this paper. The results revealed that the RP, •OH, and NO2− radicals had synergistic promoting effects, and polysaccharides with a strong antioxidant ability may have excellent hypoglycemic and hypolipidemic effects. Collectively, these results suggest that LPP has a strong bio-activity, and that Lonicera caerulea L. pomace can be used as a potential polysaccharide source.

Adipose tissue macrophages in remote modulation of hepatic glucose production.

Hepatic glucose production (HGP) is fine-regulated via glycogenolysis or gluconeogenesis to maintain physiological concentration of blood glucose during fasting-feeding cycle. Aberrant HGP leads to hyperglycemia in obesity-associated diabetes. Adipose tissue cooperates with the liver to regulate glycolipid metabolism. During these processes, adipose tissue macrophages (ATMs) change their profiles with various physio-pathological settings, producing diverse effects on HGP. Here, we briefly review the distinct phenotypes of ATMs under different nutrition states including feeding, fasting or overnutrition, and detail their effects on HGP. We discuss several pathways by which ATMs regulate hepatic gluconeogenesis or glycogenolysis, leading to favorable or unfavorable metabolic consequences. Furthermore, we summarize emerging therapeutic targets to correct metabolic disorders in morbid obesity or diabetes based on ATM-HGP axis. This review puts forward the importance and flexibility of ATMs in regulating HGP, proposing ATM-based HGP modulation as a potential therapeutic approach for obesity-associated metabolic dysfunction.

Effects of Coix Seed Extract, Bifidobacterium BPL1, and Their Combination on the Glycolipid Metabolism in Obese Mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism via different modes of action. We tested the effects of CSE, Bifidobacterium BPL1, and their combination to determine their effects on glycolipid metabolism in obese mice. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. Obese mice were selected and divided into four groups: the model control group and three intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31 g, vs. HFD mice 42.23 g) and epididymal (lower about 0.37 g, vs. HFD mice 2.5 g) and perirenal fat content (lower about 0.47 g, vs. HFD mice 0.884 g); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. CSE, BPL1 and their combination can effectively control the weight gain in obese mice, reduce fat content, and regulate blood lipids and abnormal blood sugar. These results may be related to reduce the chronic inflammatory states, improve energy metabolism, exercise, relieve insulin sensitivity, and reduce lipid synthesis via the intervention of CSE, BPL1 and their combination. Compared with the single use of CSE alone, the combination of CSE + BPL1 can better exert the regulation function of intestinal flora, and change in the abundance of bacteria that could improve the level of inflammatory factors, such as increasing Bifidobacterium, reducing Lactococcus. Compared with the use of BPL1 alone, the combination of CSE and BPL1 can better regulate pancreatic islet and improve blood sugar. CSE may act directly on body tissues to exert anti-inflammatory effects. BPL1 and CSE + BPL1 may improve the structure and function of the intestinal flora, and reduce tissue inflammation.

Nootkatone, a Sesquiterpene Ketone From Alpiniae oxyphyllae Fructus, Ameliorates Metabolic-Associated Fatty Liver by Regulating AMPK and MAPK Signaling.

Metabolic-associated fatty liver disease (MAFLD) is becoming more common due to lifestyle changes. A long-term high-fat and high-glucose diet induces glycolipid metabolism disorders in the liver, which results in the development of MAFLD. To date, there is no specific clinically useful therapeutics for this disease. Natural products or synthetic compounds were screened and investigated to find effective agents for treating MAFLD. In this study, nootkatone (Nok), a natural sesquiterpene ketone isolated from Alpiniae oxyphyllae fructus, was explored for its potential to treat MAFLD, and underlying mechanisms were studied. Our results show that Nok dramatically ameliorated the disordered lipid and glucose metabolism in MAFLD mice, decreased fat accumulation in hepatic tissue, and improved liver injury. Inflammation, metabolic disorder, and oxidative stress were ameliorated in liver tissue based on RNA-seq transcriptome comparison between a Nok-treated group and an MAFLD model group. Furthermore, Nok significantly activated AMPK activity and inhibited MAPK activity, especially the p38 and JNK signaling pathways, in vivo based on western blot analysis. The pharmaceutical effects and potential signaling pathways impacted by Nok were also investigated in L02 cells. Nok significantly promoted the consumption of glucose and decreased the deposition of triglycerides in vitro. The p-AMPKα level was notably upregulated by Nok, indicating dramatic AMPK activation. In addition, Nok decreased the levels of p-ERK1/2, p-p38, and p-JNK. Nok also inhibited the activation of MAPK signaling and, thus, alleviated MAFLD development. Our results suggest that Nok may be useful in treating MAFLD. Nok may ameliorate MAFLD by regulating glycolipid metabolism disorders by activating AMPK and inhibiting MAPK activity. Collectively, this study suggests that Nok is an effective compound for the treatment of MAFLD.

Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway

BackgroundHypothermia is a complex pathophysiological response that can be life-threatening in low-temperature environment because of impaired thermoregulation. However, there is currently no clinically effective drugs that can prevent or treat this disease. Brown adipose tissue (BAT) activation or browning of white adipose tissue (WAT) is a promising therapeutic strategy to prevent or treat hypothermia. Atractylodes macrocephala Koidz extract (AE) and its active compound Atractylenolide III (AIII) has been reported to regulate glycolipid metabolism, which might be relevant to BAT activation. However, the thermogenic effect and mechanism of AE and AIII on adipose tissues have not been explored yet. Therefore, this study firstly investigated the role of AE and AIII on hypothermia by promoting heat production of BAT and WAT. PurposeTo explore the anti-cold effect of AE and AIII in cold exposure model and explore their biological function and mechanism underlying thermogenesis. MethodsThe effect of thermogenesis and anti-hypothermia of AE and AIII on C57BL/6J mice were evaluated with several experiment in cold environment, such as toxicity test, cold exposure test, metabolism estimation, histology and immunohistochemistry, and protein expression. Additionally, BAT, inguinal WAT (iWAT) and brown adipocytes were utilized to explore the mechanism of AE and AIII on thermogenesis in vivo and in vitro. Finally, SIRT1 agonist and inhibitor in brown adipocytes to verify that AIII activated BAT through SIRT1/PGC-1α pathway. ResultsBoth AE and AⅢ could significantly maintain the core body temperature and body surface temperature of mice during cold exposure. Besides, AE and AⅢ could significantly improve the capacity of total antioxidant and glucose, lipid metabolism of mice. In addition, AE and AIII reduced mitochondrial membrane potential and ATP content both in BAT and brown adipocytes, and decreased the size of lipid droplets. Moreover, AE and AⅢ promoted the expression of proteins related to heat production in BAT and iWAT. And AIII might activate BAT via SIRT1/PGC-1α pathway. ConclusionAE and AⅢ were potential candidate drugs that treated hypothermia by improving the heat production capacity of the mice. Mechanistically, they may activate SIRT1/PGC-1α pathway, thus enhancing the function of BAT, and promoting the browning of iWAT, to act as anti-hypothermia candidate medicine.

Glycosides and flavonoids from the extract of Pueraria thomsonii Benth leaf alleviate type 2 diabetes in high-fat diet plus streptozotocin-induced mice by modulating the gut microbiota.

Twenty glycoside derivatives and nine flavonoids from the leaves of Pueraria (P. thomsonii) were isolated by column chromatography and characterized by nuclear magnetic resonance spectroscopy (NMR) and high performance liquid chromatography (HPLC). The contents of twenty glycosides and nine flavonoids from the extract of P. thomsonii leaf (PL) were 173.3 mg g-1 and 134.7 mg g-1, respectively. Two flavonoids with the highest content were robinin (49.28 mg g-1) and puerarin (42.87 mg g-1). Six flavonoids, i.e. puerarin, robinin, rutin, quercetin, quercitrin, and kaempferol showed more inhibitory effects against α-glucosidase than acarbose. PL could effectively increase the level of insulin, decrease the content of fasting blood glucose, reduce lipid accumulation in plasma, ameliorate oxidative injury and inflammation, and relieve liver and kidney damage in diabetic mice. Moreover, PL could increase intestinal probiotics to improve metabolic disorders caused by diabetes and decrease the level of Clostridium celatum to relieve inflammation. This study suggested that PL or its glycoside derivatives and flavonoids regulating glycolipid metabolism and inflammation levels might have the potential to be used to control type 2 diabetes.

Mechanisms of Dangua Recipe in Improving Glycolipid Metabolic Disorders Based on Transcriptomics.

To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics. Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A1c (HbA1c), plasma total cholesterol and triglycerides were detected. Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA1c, triglyceride and total cholesterol levels in the diabetic rats (P<;0.05 or P<;0.01); while all the above-mentioned levels (except triglyceride) were decreased significantly by GEN-617 combined with DGR intervention (P<;0.05 or P<;0.01). Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.

Integrating network pharmacology and non-targeted metabolomics to explore the common mechanism of Coptis Categorized Formula improving T2DM zebrafish

Ethnopharmacological relevanceCoptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases. Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. Aim of the studyBased on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. Materials and methodsFirstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. ResultsA total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine, baicalin, coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications, mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. ConclusionOur research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.

Identification of potential pathways whereby dietary L-tryptophan ameliorates the glucose metabolic disorder of blunt snout bream through long non-coding RNAs

The blunt snout bream (Megalobrama amblycephala) is prone to a glucose metabolic disorder when it is exposed to a high-carbohydrate diet over a long period of time. The purpose of this study was to determine whether dietary L-tryptophan (L-trp) improves glucose regulation in blunt snout bream via effects on long non-coding RNAs (lncRNAs). Fish were fed a normal-carbohydrate diet (CN), a high-carbohydrate diet (HC), or a high-carbohydrate diet supplemented with L-trp (CL) for 9 weeks, then high-throughput sequencing was used to analyze hepatic RNA libraries. Totals of 4951 lncRNAs and 8357 mRNAs were identified. Of these, 189 differentially expressed lncRNAs and 634 differentially expressed mRNAs were identified, some of which were validated using qPCR. Enrichment analysis of the mRNAs that were co-expressed with lncRNAs identified 32 potential cis-regulatory and 892 potential trans-regulatory relationships. Functional analysis showed that these co-expressed genes were represented in 151 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including 8 cis-KEGG enrichment pathways and 143 trans-KEGG enrichment pathways. Of the top 20 significant trans-enriched pathways, most were related to glucose metabolism, L-trp metabolism, and lipid metabolism, which suggested that L-trp might regulate glycolipid metabolism. The significantly differentially expressed mRNAs and lncRNAs that were upregulated in the HC group and downregulated in the CL group were used to construct a co-expression network. In total, 15 lncRNAs and 13 mRNA genes were included in this network, and most of the target genes were involved in the amelioration of insulin resistance and the maintenance of glucose homeostasis. Thus, we have generated a catalog of hepatic lncRNAs for the blunt snout bream and laid the foundation for further research into the regulation of glucose metabolism by dietary L-trp-induced lncRNAs.

Ameliorating effect on glycolipid metabolism and chemical profile of Millettia speciosa champ. extract

Ethnopharmacological relevanceMillettia speciosa Champ., also called Niu dali, is a fabaceous medicinal plant mainly distributed in southeast China, where it is a functional food for developing physical strength, and often used traditionally in medicinal treatment of numbness of the wrists, diabetes, hepatitis, and so on. Aim of the studyTo investigate the chemical profile, ameliorating effects of MSC on glycolipid metabolism in diabetic mice and to identify the possible mechanism of action. Materials and methodsHigh-performance liquid chromatography coupled with electrospray ionization quadrupole time of flight mass spectrometry (HPLC-ESI-QTOF-MS) was applied to analyze the chemical compositions from M. speciosa extract (MSC). MSC was orally administered to high-fat diet and STZ-induced diabetic mice at doses of 4.55, 9.10 and 13.65 mg/(kg·d) respectively for 10 weeks. Indices of glycolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI), blood lipids, HPA-axis hormones, and related gene expressions were evaluated. Results86 compounds were tentatively identified from MSC, counting for 91.97% of the total extract, mainly including 23 alkaloids (including 2 cyanogenetic glycosides firstly identified in this species, total content accounted to 39.71%), 23 flavonoids (11.91%), 17 acids (including 3 amino acids, 9 phenolic acids and 5 organic acids; 9.2%), 9 terpenoids and steroids (20.13%), 7 esters (3.33%), 3 lignans (3.73%), 3 saccharides (4.0%) and 1 anthraquinone (0.18%). MSC could ameliorate the glycolipid disorder in diabetic mice markedly, and significant regulations on CRH and ACTH hormones were observed. Moreover, the cellular morphology of liver and pancreas were significantly improved and the expressions of IRS2, PI3K, Akt and GLUT4 were significantly up-regulated by MSC treatment. ConclusionThis was the first time to study the chemical profile and ameliorating effect on glycolipid metabolism of M. speciosa. It was found to be rich in flavonoids and alkaloids, which might support the potential relation of material foundation and the activity in regulating glycolipid metabolism. The ameliorating effect on glycolipid disorder in diabetic mice might be associated to the regulation of related hormones of the HPA axis and the IRS2/PI3K/Akt/GLUT4 signalling pathway. It was of great significance for advanced directed separation and pharmacological activity research of MSC.

A Powerful HPLC-ELSD Method for Simultaneous Determination of Fecal Bile Acids in T2DM Rats Interfered by Sanhuang Xiexin Tang.

Bile acids (BAs) as important endogenous ligands can activate farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) signaling to regulate glycolipid metabolism. In this study, a simple, reliable and sensitive analysis method for simultaneous determination of four BAs from rat feces based on high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. Chromatographic analysis was performed with the mobile phases of acetonitrile and 0.2% formic acid. All the standard curves exhibited good linearity (R2≥0.99). The relative standard deviations of precision, stability and repeatability varied from 1.27 to 3.96%, 2.20 to 3.89% and 3.00 to 4.31%, respectively. The validated method was successfully applied to investigate the variation of four BAs in feces from T2DM rats after oral administration of Sanhuang Xiexin Tang (SXT). Data showed that SXT could remarkably increase the contents of conjunct BAs and decrease the contents of free BAs, which might contribute to ameliorate the symptoms of T2DM rats.

Processed rehmanniae radix can improve cold syndrome damage of rats by regulating glycolipid metabolism

Background: The traditional chinese medicine have medicinal property,and the property of the drug has been found to be mostly related to the body's substance and energy metabolism. Objectives: The present study intended to assess the drug property of Rehmanniae Radix Praeparata (PRR), called Shudihuang in traditional Chinese medicine and to discover its mechanism of cold syndrome in rats. Materials and Methods: Through the creation of a typical cold syndrome animal model, the appearance score, body weight, rectal temperatures, and survival rate of the animals treated were evaluated at different time points. Several indices in vivo correlated with glycolipid metabolism (glucose transporters (GLUT- 4), fructose phosphate kinase (PFK- 2), glycogen synthetase (GS), acetyl- CoA carboxylase 1 (ACC1), acetyl- CoA carboxylase 2 (ACC2), hydroxy methylglutaryl coenzyme A (HMG CoA) and hormone- sensitive lipase (HSL) were determined; Western blot is used to analyze of phosphorylated amp- dependent protein kinase (p- AMPK) appearance in liver tissues. Results: Compared with the normal group, the levels of GLUT- 4, PFK- 2, GS, ACC1, ACC2, HMG- CoA, and HSL in the model group all reduced significantly and p- AMPK protein expression diminished. Compared with the model group, PRR can significantly relapse to GLUT- 4, PFK- 2, GS, ACC1, ACC2, HMG- CoA, and HSL (P < 0.01 or P < 0.05) and rise the expression of p- AMPK. RR could suggestively diminution the level of these indices (P < 0.01 or P < 0.05). Conclusion: Drug property of PRR was inferred as trending to “heat and warm,” which still essential for further study. PRR may recover the metabolic function of the cold syndrome model rats by distressing the process of glycolipid metabolism which is by triggering the AMPK signaling pathway.

Selection and evaluation of quality control markers in propolis based on its hyperlipidemia therapy via regulating PXR/CYP3A4 expression

BackgroundPropolis and its preparations are components of TCM and functional food sources for antihyperlipidemia therapy. However, due to the metabolic properties of propolis, its individual components remain ambiguous, especially those that are therapeutically active. PurposeThe study presented here identified the primary target (PXR/CYP3A4) of propolis activity against hyperlipidemia and evaluated individual compounds of propolis to select a quality control marker based on this activity. MethodsMice fed a high-fat diet were used to study the efficacy of propolis, followed by identification of substantially influenced glycolipid regulatory target(s) by propolis. Since propolis had the strongest effect on PXR expression, we took advantage of its downstream target CYP3A4, the drug metabolism activity of such enzyme is affected by alterations in PXR expression. Thus, we used the production of 1’-hydroxy-midazolam as an indicator. Compounds found by UHPLC-TOF-MS were added to a HepG2 cell solution (transfected by PXR mRNA and the CYP3A4 plasmid to simulate drug metabolism in the body) in the form of a monomer, followed by the addition of midazolam. Changes in the amount of “indicator” were used to investigate each compound's qualitative (promote or suppress) and quantitative activity. Compounds with obvious effects were quantified in propolis extract, as confirmed via Western Blot analysis regarding their PXR regulatory activity, and subjected to pharmacokinetic analysis to biter understand their metabolism in the body. Finally, components passing these screens could be regarded as quality control markers capable of indicating the efficacy of antihyperlipidemic activity via PXR/CYP3A4 regulation. ResultsThe use of propolis was effective in lowering TG and TC levels in mice, as well as in repairing their injured livers; its activity was comparable to the chemical and TCM positive controls. Propolis mainly suppressed PXR expression compared with other regulatory targets that were tested. Most of the individual compounds from propolis (13 out of 15) showed obvious regulatory activity of PXR/CYP3A4; however, content quantification and pharmacokinetic analyses narrowed the selection to 2 compounds, kaempferol and chrysin, as the main active components responsible for the antihyperlipidemic effect of propolis. In other words, this study suggested that propolis mainly acts on the PXR/CYP3A4 pathway to regulate glycolipid metabolism, and the 2 compounds mentioned above can be used as quality control markers (QM) to evaluate the efficacy of this activity. ConclusionPropolis's antihyperlipidemic effect relies on its regulation of PXR/CYP3A4 expression. Kaempferol and chrysin can be regarded as QMs. In addition, the metabolite-based method for evaluating regulatory activity is much faster, more effective, and more reliable than the conventional screening method, paving the way for its future applications.

Dietary Ginsenoside T19 Supplementation Regulates Glucose and Lipid Metabolism via AMPK and PI3K Pathways and Its Effect on Intestinal Microbiota.

Ginseng, as a functional food, is widely used worldwide because of its multifarious benefits. Studies have verified that 25-hydroxyl-protopanaxatriol (T19) is a new ginsenoside from ginseng, which had an important inhibitory effect on α-glucosidase and protein tyrosine phosphatase 1B in vitro. This study aims to assess the regulation of T19 against glycolipid metabolism by insulin-resistant HepG2 cells and diabetes mice induced with high-fat diet combined with streptozotocin (STZ). T19 effectively lowered the levels of blood glucose and lipid, alleviated insulin resistance, and improved histological pathology of liver and pancreas. Further study demonstrated that regulation of AMP-activated protein kinase- and phosphoinositide-3-kinase-signaling pathways was involved in the potential mechanism of T19 efficiency. Simultaneously, high-throughput sequencing of 16S rDNA revealed that T19 remarkably ameliorated the high-fat diet/STZ-induced disorders of intestinal microbiota by decreasing the value of Firmicutes/Bacteroidetes, and remarkably raised the relative abundance of the Lachnospiraceae family, which are the beneficial bacteria that can regulate glucose and lipid metabolism. The results may provide clues for further understanding the mechanism of T19 in regulating glycolipid metabolism, and may provide a scientific basis for ginseng as a potential dietary food to prevent metabolic diseases.

Fibronectin type III domain-containing 5 in cardiovascular and metabolic diseases: a promising biomarker and therapeutic target.

Cardiovascular and metabolic diseases are the leading causes of death and disability worldwide and impose a tremendous socioeconomic burden on individuals as well as the healthcare system. Fibronectin type III domain-containing 5 (FNDC5) is a widely distributed transmembrane glycoprotein that can be proteolytically cleaved and secreted as irisin to regulate glycolipid metabolism and cardiovascular homeostasis. In this review, we present the current knowledge on the predictive and therapeutic role of FNDC5 in a variety of cardiovascular and metabolic diseases, such as hypertension, atherosclerosis, ischemic heart disease, arrhythmia, metabolic cardiomyopathy, cardiac remodeling, heart failure, diabetes mellitus, and obesity.