The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Sertoli cells play an important role in the process of spermatogenesis, and the abnormalities in spermatogenesis are closely related to disruptions in glycolipid metabolism. The metabolic environment of Sertoli cells is hypoxic, with glycolysis and fatty acid β-oxidation being the primary metabolic pathways. In Sertoli cells, glycolysis produces lactate to provide energy for spermatogenic cells, while fatty acid β-oxidation generates ATP. Currently, the relationship between glycolipid metabolism in Sertoli cells and spermatogenic cell development, as well as the interplay between glucose and lipid metabolism remain unclear. Various hormones, including sex hormones, can affect glucose metabolism in Sertoli cells by endocrine regulation. The activation or inhibition of signaling pathways such as AMPK, mTOR, and Akt can alter the expression levels of glycolysis-related transporter genes and the synthesis of fatty acids, thereby affecting glycolipid metabolism in Sertoli cells. Some transcription factors such as PPARγ can regulate downstream fatty acid metabolism-related genes by directly binding to their response elements and promoting the oxidation of fatty acids in Sertoli cells. In this article we elaborate on the key factors influencing glycolipid metabolism in Sertoli cells and their interconnections, as well as their potential clinical implications, offering new insights for precisely targeted treatments of male infertility.
Sertoli Cells/cytology* ; Male ; Glycolipids/metabolism* ; Spermatogenesis/physiology* ; Humans ; Lipid Metabolism ; Animals ; Fatty Acids/metabolism* ; Signal Transduction ; Glycolysis

The fatty acid desaturase 2 (FADS2) gene encodes delta-6 desaturase (D6D) and is a member of the fatty acid desaturase gene family.D6D is the key enzyme catalyzing the transformation of linoleic acid and α-linolenic acid to long-chain polyunsaturated fatty acid (LC-PUFA).LC-PUFA play a crucial role in regulating the glycolipid metabolism of living organisms.In recent years,the activity of D6D and the single nucleotide polymorphism (SNP) of FADS2 gene have become a hot topic in the research on glycolipid metabolism.This article reviews the role of FADS2 gene in glycolipid metabolism.
Fatty Acid Desaturases/metabolism* ; Glycolipids/metabolism* ; Humans ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the protective effects of modified Linggui Zhugan Decoction (, MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus (T2DM) rats. METHODS: Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2DM (ob-T2DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M, 9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups, 10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance (IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1 )/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) pathways were also studied. RESULTS: MLZD dose-dependently reduced fasting blood glucose, fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (P<0.05 or P<0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways and restored the tissue structure of liver and pancreas (P<0.05 or P<0.01). CONCLUSIONS MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/drug therapy* ; Glycolipids ; Inflammation ; Obesity/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

OBJECTIVE: This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation. METHODS: Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM. RESULTS: A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells. CONCLUSION Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinase/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Glycolipids/therapeutic use* ; Network Pharmacology ; Plant Extracts/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use*

Adenosine 5'-monophosphate-activated protein activated protein kinase (AMPK), a heterotrimeric complex, is an important kinase to regulate glycolipid metabolism and energy balance involved in a variety physiological processes in human body. Many research indicated that the function and activity of AMPK were closely related to inflammation, diabetes and cancers. Recent reports show that inhibition of metformin (a first-line drug) on hepatic glucose in patients with hyperglycemia is associated with AMPK pathway, suggesting that targeting AMPK may be one of the effective strategies for the prevention and treatment of a variety of chronic diseases. Here, we review research progress on the structure, activation and regulation of AMPK in glycolipid metabolism to provide an insight into the basic and clinical research of diabetes therapy.
AMP-Activated Protein Kinases ; Adenosine ; Adenosine Monophosphate ; Energy Metabolism ; Enzyme Activation ; Glycolipids ; Humans

The bitter taste is one of the important properties among five flavors of Chinese materia medica (CMM), characterized by downbearing and discharging, drying dampness, and consolidating Yin. In common CMM, bitter-taste CMM accounts for a large proportion, indicating the importance of it. Through the efficacy of clearing away heat and dampness, reducing fire and removing toxin, bitter-taste CMM has achieved good results in treating diabetes in clinical application, proving their definite therapeutic effect on regulating glucose and lipid metabolism (main features of diabetes). At present, there are many reports about the chemical constituents and pharmacological effects of CMM on diabetes, but there are few reviews on the chemistry and biology of bitter-taste CMM. This study summarized the properties and compatibility characteristics of bitter-taste CMM for treating diabetes, and mainly analyzed the chemistry and biology basis of bitter-taste CMM with function of regulating glycolipid metabolism, laying foundation for further researches on properties theory of CMM.
Glycolipids ; metabolism ; Materia Medica ; chemistry ; Medicine, Chinese Traditional ; Research ; Taste

Rhamnolipid biosurfactant is mainly produced by Pseudomonas aeruginosa that is the opportunistic pathogenic strain and not suitable for future industrial development. In order to develop a relatively safe microbial strain for the production of rhamnolipid biosurfactant, we constructed engineered Escherichia coli strains for rhamnolipid production by expressing different copy numbers of rhamnosyltransferase (rhlAB) gene with the constitutive synthetic promoters of different strengths in E. coli ATCC 8739. We further studied the combinatorial regulation of rhlAB gene and rhaBDAC gene cluster for dTDP-1-rhamnose biosynthesis with different synthetic promoters, and obtained the best engineered strain-E. coli TIB-RAB226. Through the optimization of culture temperature, the titer of rhamnolipd reached 124.3 mg/L, 1.17 fold higher than that under the original condition. Fed-batch fermentation further improved the production of rhamnolipid and the titer reached the highest 209.2 mg/L within 12 h. High performance liquid chromatography-mass spectrometry (LC-MS) analysis showed that there are total 5 mono-rhamnolipid congeners with different nuclear mass ratio and relative abundance. This study laid foundation for heterologous biosynthesis of rhanomilipd.
Bacterial Proteins ; genetics ; Batch Cell Culture Techniques ; Decanoates ; Escherichia coli ; metabolism ; Fermentation ; Glycolipids ; biosynthesis ; Hexosyltransferases ; genetics ; Industrial Microbiology ; methods ; Multigene Family ; Promoter Regions, Genetic ; Pseudomonas aeruginosa ; Rhamnose ; analogs & derivatives ; biosynthesis ; Surface-Active Agents ; metabolism

OBJECTIVETo investigate the effect of Dan-gua Fang on adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism.

METHODSForty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPKα mRNA was assessed by real-time PCR. AMPKα and phospho-AMPKα protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded.

RESULTSSimilar AMPKα mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups (P<0.05). AMPKα protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPKα (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group (P<0.05), respectively. However, phosphor-AMPKα/AMPKα ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly.

CONCLUSIONDan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.

AMP-Activated Protein Kinases ; genetics ; metabolism ; Animals ; Blood Glucose ; metabolism ; Body Weight ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; enzymology ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Feeding Behavior ; Glycolipids ; metabolism ; Liver ; enzymology ; pathology ; Male ; Phosphorylation ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Time Factors

Biosurfactants (BSs) are highlighted owing to their multiple advantages in diverse applications. To screen a superior strain that producing a blend-biosurfactant of lipopeptide and glycolipid, the hemolytic activity assay on blood agar plates, the modified oil-red spreading test and MALDI-TOF Mass Spectrometry identification of the purified products was carried out. Bacillus subtilis THY-7 was selected and its principal products were surfactin and dirhamnolipid. The medium component and culture conditions of THY-7 were optimized by both single factor and orthogonal experiments. After 48 h optimal batch culture in flask, the cell density (OD600) was 37.0 and the product titer was 2.4 g/L, which was 3.4 folds and 3.1 folds of that under original condition, respectively. A fed-batch culture in a 5 L fermentor was further performed coupling with in situ recovery of foam, in which the titer of blend-BS increased to 4.5 g/L at 25 h. Quantification by HPLC and anthrone colorimetry revealed that surfactin and dirhamnolipid accounted for 74% and 22% of the blend-BS, respectively.
Bacillus subtilis ; growth & development ; isolation & purification ; metabolism ; Chromatography, High Pressure Liquid ; Culture Media ; Glycolipids ; biosynthesis ; Industrial Microbiology ; Lipopeptides ; biosynthesis ; Surface-Active Agents ; metabolism