Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

This study aimed to explore alterations in growth performance, glycolipid metabolism disorders, intestinal mucosal barrier, cecal microbiota community, and metabolites in a chronic corticosterone (CORT)-induced stress (CCIS) broiler model. Results showed that compared with control (CON) broilers, in CCIS broilers: (i) the final body weight (BW), BW gain, and average daily gain were significantly reduced. (ii) The glycolipid metabolism disorder and impairement of intestinal immune barrier and physical barrier function were observed. (iii) Diversity and richness of cecal microbiota were obviously increased. From phylum to genus level, the abundances of Firmicutes and Faecalibacterium were significantly decreased, while the abundances of Proteobacteria, RuminococcaceaeUCG-005, and Escherichia coli (Shigella) were significantly increased. Microbial network analysis and function pathways prediction showed that cecal microbiota was mainly concentrated in translation, metabolism, nucleotide metabolism, and endocrine system. (iv) The main differential metabolites identified include steroids and their derivatives, amino acids, fatty acids, and carbohydrates; among which 37 metabolites were significantly upregulated, while 27 metabolites were significantly downregulated. These differential metabolites were mainly enriched in pathways related to steroid hormone biosynthesis and tyrosine metabolism. (v) Correlation between cecal microbiota and glycolipid metabolism indexes showed that BW and total cholesterol (TC) were positively correlated with Christensenellaceae_R.7_group and Escherichia_Shigella, respectively. Furthermore, the downregulated Faecalibacterium and Christensenellaceae were negatively correlated with the upregulated differentially expressed metabolites. These findings suggested that CCIS altered cecal microbiota composition and metabolites, which led to glycolipid metabolism disorder and impaired the nutritional metabolism and immune homeostasis, providing a theoretical basis for efforts to eliminate the harm of chronic stress to human health and animal production.
OBJECTIVE: The study aimed to determine the influence of altered intestinal mucosal barrier, cecum flora community, and metabolites on anti-growth performance, glycolipid metabolism disorders of chronic corticosterone (CORT)-induced stress (CCIS) broilers. Compared with control (CON) broilers, in CCIS broilers: (i) anti-growth performance, glycolipid metabolism disorder, and impaired intestinal immune barrier and physical barrier function were observed. (ii) From phylum to genus level, the abundances of Firmicutes and Faecalibacterium were decreased; whereas, the abundances of Proteobacteria, RuminococcaceaeUCG-005, and Escherichia coli (Shigella) were increased. (iii) Differential metabolites in cecum were mainly enriched in steroid hormone biosynthesis and tyrosine metabolism. (iv) Body weight (BW) and total cholesterol (TC) were positively correlated with Christensenellaceae_R.7_group and Escherichia_Shigella, respectively, while downregulated Faecalibacterium and Christensenellaceae were negatively correlated with upregulated metabolites. Our findings suggest that CCIS induces anti-growth performance and glycolipid metabolism disorder by altering cecum flora and metabolites, providing a theoretical basis for efforts to eliminate the effect of chronic stress on human health and animal production.

Type 2 diabetes mellitus (T2DM) is a complex disease caused by multiple factors, which are often accompanied by the disorder of glucose and lipid metabolism and the lack of vitamin D.Over the years, researchers have conducted numerous studies into the pathogenesis and prevention strategies of diabetes. In this study, diabetic SD rats were randomly divided into type 2 diabetes group, vitamin D intervention group, 7-dehydrocholesterole reductase (DHCR7) inhibitor intervention group, simvastatin intervention group, and naive control group. Before and 12 weeks after intervention, liver tissue was extracted to isolate hepatocytes. Compared with naive control group, in the type 2 diabetic group without interference, the expression of DHCR7 increased, the level of 25(OH)D3 decreased, the level of cholesterol increased. In the primary cultured naive and type 2 diabetic hepatocytes, the expression of genes related to lipid metabolism and vitamin D metabolism were differently regulated in each of the 5 treatment groups. Overall, DHCR7 is an indicator for type 2 diabetic glycolipid metabolism disorder and vitamin D deficiency. Targeting DHCR7 will help with T2DM therapy.The management model of comprehensive health intervention can timely discover the disease problems of diabetes patients and high-risk groups and reduce the incidence of diabetes.

Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.

Berberine is a natural active ingredient extracted from the rhizome of Rhizoma Coptidis, which interacts with multiple intracellular targets and exhibits a wide range of pharmacological activities. Previous studies have preliminarily confirmed that the regulation of mitochondrial activity is related to various pharmacological actions of berberine, such as regulating blood sugar and lipid and inhibiting tumor progression. However, the mechanism of berberine\'s regulation of mitochondrial activity remains to be further studied. This paper summarizes the molecular mechanism of the mitochondrial quality control system and briefly reviews the targets of berberine in regulating mitochondrial activity. It is proposed that berberine mainly regulates glycolipid metabolism by regulating mitochondrial respiratory chain function, promotes tumor cell apoptosis by regulating mitochondrial apoptosis pathway, and protects cardiac function by promoting mitophagy to alleviate mitochondrial dysfunction. It reveals the mechanism of berberine\'s pharmacological effects from the perspective of mitochondria and provides a scientific basis for the application of berberine in the clinical treatment of diseases.

UNASSIGNED: Studies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process.
UNASSIGNED: The study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated.
UNASSIGNED: Three-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects.
UNASSIGNED: Taken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.

Chitooligosaccharides (COS) have a variety of biological activities due to their positively charged amino groups. Studies have shown that COS have antidiabetic effects, but their molecular mechanism has not been fully elucidated. The present study confirmed that COS can reduce hyperglycemia and hyperlipidemia, prevent obesity, and enhance histological changes in the livers of mice with type 2 diabetes mellitus (T2DM). Additionally, treatment with COS can modulate the composition of the gut microbiota in the colon by altering the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. Furthermore, in T2DM mice, treatment with COS can upregulate the cholesterol-degrading enzymes cholesterol 7-alpha-hydroxylase (CYP7A1) and incretin glucagon-like peptide 1 (GLP-1) while specifically inhibiting the transcription and expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the key enzyme in cholesterol synthesis. Furthermore, using an oleic acid-induced hepatocyte steatosis model, we found that HMGCR can be directly transactivated by SET and MYND domain containing 3 (SMYD3), a transcriptional regulator, via 5\'-CCCTCC-3\' element in the promoter. Overexpression of SMYD3 can suppress the inhibitory effect of COS on HMGCR, and COS might regulate HMGCR by inhibiting SMYD3, thereby exerting hypolipidemic functions. To the best of our knowledge, this study is the first to illustrate that COS mediate glucose and lipid metabolism disorders by regulating gut microbiota and SMYD3-mediated signaling pathways.