The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon

The aim of this study was to evaluate the effects of butyrolactone‐I (A6) on type 2 diabetes (T2D) in db/db mice because A6 was found to inhibit α‐glucosidase activities and TNF‐α release, which were associated with improving T2D. Male db/db mice were divided into 6 groups and given an equivalent volume of olive oil, acarbose, or different doses of A6 for 4 wk (n = 8/group). In this study, 11 butenolide derivatives were screened for their α‐glucosidase and TNF‐α suppressive activity in vitro. A6, an efficient α‐glucosidase inhibitor, exerts hypoglycemic and multiple activities in reducing weight, improving glucose tolerance and insulin resistance, increasing short‐chain fatty acid (SCFA) levels, activating SCFA‐induced increases in glucagon‐like peptide 1 and peroxisome proliferator‐activated receptor‐γ expression, enhancing intestinal mucosal barrier function and mitigating endoxemia in db/db mice. These effects may result from mediation of gut microbiota by A6. Meanwhile, A6, with potent TNF‐α–lowering properties, was demonstrated to have multiple salutary effects with excellent structural stability and long‐term safety in vivo. A6, an effective α‐glucosidase inhibitor with high security and stability, exerted potent antidiabetic effects in vivo. Furthermore, the modulation of gut microbiota of A6 was demonstrated to be one of the mechanisms contributing to anti‐inflammation properties and improving endoxemia. Our work confirms that the compound A6 is a prospective drug candidate for T2D.—Wu, W., Liu, L., Zhu, H., Sun, Y., Wu, Y., Liao, H., Gui, Y., Li, L., Liu, L., Sun, F., Lin, H. Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice. FASEB J. 33, 12616–12629 (2019). http://www.fasebj.org

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“…SCFAs can activate the GLP‐1 signaling pathway (35). Furthermore, we found that compound A6 increased SCFA of mouse feces.…”

Section: Resultsmentioning

confidence: 99%

Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice

Liu

Zhu

et al. 2019

The FASEB Journal

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“…Our results are consistent with previously reported effect of butyrate or SCFAs on the intestinal function, obesity, and NAFLD. SCFAs have also been reported to show antiobesity effect in animal models, through affecting the secretion of glucagon‐like peptide‐1 and peptide tyrosine tyrosine in the intestine (Christiansen et al, ). I has also been reported that the probiotic mixture of Lactobacillus and Bifidobacterium alleviates inflammation in NAFLD rats through the action of metabolite butyrate (Liang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Gut–liver on a chip toward an in vitro model of hepatic steatosis

Lee

Sung

2018

Biotech & Bioengineering

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Hepatic steatosis is a process of abnormal lipid deposition within the liver cells, often caused by excessive alcohol uptake or obesity. A conventional in vitro model for hepatic steatosis uses a liver cell culture, treated with fatty acids and measures accumulation of lipids within the cells. This model does not recapitulate the complex process of absorption and metabolism of digestive lipids. Here, we introduce a gut-liver chip, which mimics the gut absorption and hepatic metabolism in a microfluidic chip. Absorption of fatty acids through gut layer and subsequent deposition within liver cells was demonstrated. Tumor necrosis factor-α, butyrate, and α-lipoic acid were chosen as model molecules that can affect hepatic steatosis via different mechanisms, and their effects were evaluated. Our results suggest that the gut-liver chip can mimic the absorption and accumulation of fatty acids in the gut and the liver.

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“…Through luminal and especially vascular infusion of acetate, propionate and butyrate, they observed that acetate and butyrate increased colonic glucagon-like peptide-1 (GLP-1) secretion with increased intracellular cAMP concentrations but independent in FFAR2/FFAR3 activation. The results suggested that all blood circulation, nerve and paracrine might play a part in the SCFAs-stimulated GLP-1 secretion [34]. Another research demonstrated that SCFAs decreased food take by activating vagal afferent via intraperitoneal injection of three SCFA molecules (acetate, propionate and butyrate) in fasted mice and switching off the vagal afferents of hepatic branch and capsaicin-sensitive sensory nerves [35].…”

Section: Scfasmentioning

confidence: 95%

Clostridium species as probiotics: potentials and challenges

Guo

Zhang

et al. 2020

J Animal Sci Biotechnol

305

228

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Clostridium species, as a predominant cluster of commensal bacteria in our gut, exert lots of salutary effects on our intestinal homeostasis. Up to now, Clostridium species have been reported to attenuate inflammation and allergic diseases effectively owing to their distinctive biological activities. Their cellular components and metabolites, like butyrate, secondary bile acids and indolepropionic acid, play a probiotic role primarily through energizing intestinal epithelial cells, strengthening intestinal barrier and interacting with immune system. In turn, our diets and physical state of body can shape unique pattern of Clostridium species in gut. In view of their salutary performances, Clostridium species have a huge potential as probiotics. However, there are still some nonnegligible risks and challenges in approaching application of them. Given this, this review summarized the researches involved in benefits and potential risks of Clostridium species to our health, in order to develop Clostridium species as novel probiotics for human health and animal production.

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The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon

Cited by 275 publications

References 69 publications

Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice

Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice

Gut–liver on a chip toward an in vitro model of hepatic steatosis

Clostridium species as probiotics: potentials and challenges

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