Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice

Zhang, Ya; Yang, Cheng; Liu, Jian; Zuo, Jihui; Yan, Liping; Thring, Ronald W.; Ba, Xueqing; Qi, Dake; Wu, Mingjiang; Gao, Yitian; Tong, Haibin

doi:10.1016/j.redox.2022.102481

Cited by 19 publications

(12 citation statements)

References 46 publications

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“…However, the precise regulatory mechanism underlying fucoidan‐induced activation of the Nrf2/ARE signaling pathway remains unclear. In a previous study (Zhang, Cheng, et al, 2022), we revealed the intricate molecular mechanisms by which metformin activates Nrf2/ARE, which could serve as a reference for elucidating the pharmacological mechanism of SP‐Fuc. We found that metformin significantly increased the accumulation of tauroursodeoxycholic acid (TUDCA) by remodeling the gut microbiota, reducing the abundance of Bifidobacterium and the activity of bile salt hydrolase.…”

Section: Discussionmentioning

confidence: 91%

“…However, the precise regulatory mechanism underlying fucoidan-induced activation of the Nrf2/ARE signaling pathway remains unclear. In a previous study (Zhang, Cheng, et al, 2022), we revealed the intricate molecular mechanisms by which metformin activates Nrf2/ARE, which could in a single-site, double-blind, randomized, placebo-controlled trial (Wright et al, 2019). Another clinical study (Sakai et al, 2019) conducted a double-blind, randomized, placebo-controlled, crossover trial in 30 patients with T2DM received high-molecular-weight fucoidan (1620 mg/day for 12 weeks).…”

Section: Discussionmentioning

confidence: 99%

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Fucoidan derived from Sargassum pallidum alleviates metabolism disorders associated with improvement of cardiac injury and oxidative stress in diabetic mice

Lin

Wang

Yan

et al. 2023

Phytotherapy Research

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Type 2 diabetes mellitus (T2DM) and its complications have become a serious global health epidemic. Cardiovascular complications have considered as a major cause of high mortality in diabetic patients. Fucoidans from brown algae have diverse medicinal activities, however, few studies reported pharmacological activity of Sargassum. pallidum fucoidan (Sp‐Fuc). Therefore, the aim of this study was to investigate the effects of Sp‐Fuc on diabetic symptoms and cardiac injury in spontaneous diabetic db/db mice. SP‐Fuc at 200 mg/(kg/d) was administered intragastrically to db/db mice for 8 weeks, the effects on hyperlipidemia, hyperglycemia, insulin resistance, and cardiac damage, as well as oxidative stress, inflammation, Nrf2/ARE, and NF‐κB signaling pathways, were investigated. Our data demonstrated that Sp‐Fuc significantly (p < 0.05) decreased body weights, hyperlipidemia, and hyperglycemia in db/db mice, along with improved insulin sensitivity. Additionally, Sp‐Fuc significantly (p < 0.05) alleviated cardiac dysfunction and pathological morphology of cardiac tissue. Sp‐Fuc also significantly (p < 0.05) decreased lipid peroxidation, increased antioxidant function, as well as reduced cardiac inflammation, possibly through Nrf2/ARE and NF‐κB signaling. Sp‐Fuc can ameliorate the metabolism disorders of glucose and lipid in diabetic mice by activating Nrf2/ARE antioxidant signaling, simultaneously reducing cardiac redox imbalance and inflammatory damage. The present findings provide a perspective on the therapy strategy for T2DM and its complications.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Fucoidan derived from Sargassum pallidum alleviates metabolism disorders associated with improvement of cardiac injury and oxidative stress in diabetic mice

Lin

Wang

Yan

et al. 2023

Phytotherapy Research

Self Cite

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“… 35 But different studies have different results regarding its regulation of blood sugar. Zhang et al 36 studied that in the ob/ob2 type diabetes mouse model, TCDCA alleviated IR, and reduced oxidative stress and intestinal inflammation. The mechanism of its action may be that TCDCA blocks the binding of KEAP1 and Nrf2, leading to Nrf2 translocation to the nucleus and initiating the transcription of antioxidant genes, ultimately reducing intracellular ROS accumulation and improving insulin signaling.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Improves Insulin Resistance in Type 2 Diabetes Mice by Regulating Intestinal Flora and Bile Acid

Pan,

Li,

Guo

et al. 2023

DMSO

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Introduction Adjusting internal organs and dredging channel electroacupuncture has a definite effect on type 2 diabetes, but the specific mechanism still needs to be further clarified. This study aims to investigate the effects of electroacupuncture on the gut microbiota and bile acids in db/db mice after the intervention of “adjusting internal organs and dredging channel” and further explore its mechanism of action in treating T2DM. Methods We used db/db mice as the animal model and db/m mice from the same litter as the blank control group, a total of 4 weeks of intervention were conducted. We evaluated the effectiveness of the “adjusting internal organs and dredging channel” treatment by detecting indicators related to glucose and lipid- metabolism. Detect changes in the gut microbiota of mice in each group using 16SrDNA sequencing technology. The content of bile acids in mouse feces was determined using liquid chromatography mass spectrometry, and the correlation analysis between different bile acids and differential bacterial communities was performed. The expression levels of TGR5 and GLP-1 proteins were measured using the Western blot method. Results Adjusting internal organs and dredging channel electroacupuncture can improve blood glucose levels in db/db mice, increase the abundance of Firmicutes and Actinobacteria, and increase the content of fecal bile acid pool heavy CA and UDCA. At the same time, it also increased the content of TGR5/GLP1 in the small intestine. Conclusion Adjusting internal organs and dredging channel electroacupuncture can improve the disorder of glucose and lipid metabolism in db/db mice, regulate the abundance and colony composition of intestinal microbiota in mice, and regulate bile acid metabolism in mice. The interaction between bile acid and intestinal microbiota can also be observed; Mutual influence may play a role in regulating blood sugar together.

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“…The lipid metabolism process in zebrafish, encompassing lipid absorption and transport, oxidative metabolism, and related processes, bears a striking resemblance to that of mammals [25], and it can also reveal the changes in lipid metabolism in fish. These benefits render zebrafish highly suitable models for investigating diseases associated with lipid metabolism, such as diabetes and NAFLD [26,27]. NAFLD is a metabolic disorder with multiple causes, long-term hyperglycemia causes macrovascular or microvascular complications, such as retinopathy [28].…”

Section: Introductionmentioning

confidence: 99%

β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model

Zhang,

Liu,

Xue

et al. 2024

Animals

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Objective: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood. Methods: A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of β-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics. Results: β-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in β-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. β-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of β-sitosterol significantly inhibited the expression of Ppar-γ and Rxr-α in the zebrafish model by at least 50% and 25%, respectively. Conclusions: β-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.

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Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice

Cited by 19 publications

References 46 publications

Fucoidan derived from Sargassum pallidum alleviates metabolism disorders associated with improvement of cardiac injury and oxidative stress in diabetic mice

Fucoidan derived from Sargassum pallidum alleviates metabolism disorders associated with improvement of cardiac injury and oxidative stress in diabetic mice

Electroacupuncture Improves Insulin Resistance in Type 2 Diabetes Mice by Regulating Intestinal Flora and Bile Acid

β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model

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