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The Effects of Erchen Decoction on Gut Microbiota and Lipid Metabolism Disorders in Zucker Diabetic Fatty Rats.

ABSTRACT: Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.

SUBMITTER: Zhao T

PROVIDER: S-EPMC8339961 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Diabetes is a very strong predictor of chronic systemic vascular diseases and acute cardiovascular events. Recently, associations between metabolic disorders and pulmonary hypertension have also been reported in both humans and animal models. In order to get some further insight into the relationship of pulmonary hypertension with obesity, insulin resistance and hyperglycemia, herein we have used the Zucker diabetic fatty rats (ZDF/clr-lepr fa) at 20 weeks fed a standard diet and compared to their lean Zucker littermates (ZL). ZDF rats were obese, had elevated plasma glucose levels and insulin resistance, i.e. a clinically relevant model of type 2 diabetes. They presented elevated systolic, diastolic and mean pulmonary arterial pressures and a parallel increase in the Fulton index. Systemic arterial pressures were also increased but the left ventricle plus septum weight was similar in both groups and the heart rate was reduced. Wall media thickening was observed in the small pulmonary arteries from the ZDF rats. Isolated pulmonary arteries mounted in a wire myograph showed similar vasoconstrictor responses to phenylephrine and 5-HT and similar responses to the endothelium-dependent vasodilator acetylcholine. However, the iNOS inhibitor 1400W enhanced the vasoconstrictor responses in ZDF but not in ZL rats. The protein expression of eNOS and iNOS was not significantly different in the lungs of the two groups. The lung expression of Bmpr2 mRNA was downregulated. However, the mRNA expression of Kcna5, Kcnk3, Kcnq1, Kcnq4 or Kcnq5, which encode for the potassium channels Kv1.5, TASK-1, Kv7.1, Kv7.4 and Kv7.5, respectively, was similar in ZL and ZDF rats. In conclusion, ZDF rats show increased pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arterial medial thickening and downregulated lung Bmpr2 despite leptin resistance. These changes were mild but are consistent with the view that diabetes is a risk factor for pulmonary hypertension.

Project description:BackgroundBerberine is a plant alkaloid that has multiple beneficial effects against intestine inflammation. In our previous study, we have found that berberine also possesses an antidiabetic effect. However, whether berberine is useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on intestine endocrine function and gut microbiota is unclear.AimTo investigate the effects of berberine in the prevention of T2DM, as well as its effects on intestine GLP-2 secretion and gut microbiota in ZDF rats.MethodsTwenty Zucker Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited impaired glucose tolerance (IGT). The rats were then divided into two groups to receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood glucose (FBG) was measured, an oral glucose tolerance test was performed, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Intestinal expression of TLR-4, NF-κB, TNF-α, mucin, zona occludens-1 (ZO-1) and occludin were assessed (immunohistochemistry). Plasma levels and glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, pyrosequencing, and bioinformatics analysis were performed.ResultsAfter 3 weeks of intervention, diabetes developed in all rats in the IGT group, but only 30% of rats in the berberine group. Treatment with berberine was associated with reductions in food intake, FBG level, insulin resistance, and plasma LPS level, as well as increases in fasting plasma GLP-2 level and glutamine-induced intestinal GLP-2 secretion. Berberine could increase the goblet cell number and villi length, and also reverse the suppressed expressions of mucin, occludin, ZO-1 and the upregulated expressions of TLR-4, NF-κB and TNF-α induced in IGT rats (P<0.05). Berberine also improved the structure of the gut microbiota and restored species diversity.ConclusionBerberine may slow the progression of prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal permeability, and the structure of the gut microbiota.

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The Effects of Erchen Decoction on Gut Microbiota and Lipid Metabolism Disorders in Zucker Diabetic Fatty Rats.

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