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Gut-liver crosstalk is an important determinant of human health with profound effects on energy homeostasis. While gut microbes produce a huge range of metabolites, specific compounds such as short chain fatty acids (SCFA) can enter the portal circulation and reach the liver, a central organ involved in glucose homeostasis and diabetes control. Propionate is a major SCFA involved in activation of intestinal gluconeogenesis (IGN), thereby regulating food intake, enhancing insulin sensitivity and leading to metabolic homeostasis. Although microbiome modulating strategies may target the increased microbial production of propionate, it is not clear whether such effect spreads through to the hepatic cellular level. Here, we designed a propionate-producing consortium using a selection of commensal gut bacteria, and we investigated how their delivered metabolites impact an enterohepatic model of insulin resistance. Glycogen storage on hepatocyte-like cells and inflammatory markers associated with insulin resistance were evaluated to understand the role of gut metabolites on gut-liver crosstalk in a simulated scenario of insulin resistance. The metabolites produced by our consortium increased glycogen synthesis by approximately 57% and decreased pro-inflammatory markers such as IL-8 by 12%, thus elucidating the positive effect of our consortium on metabolic function and low-grade inflammation. Our results suggest that microbiota-derived products can be a promising multipurpose strategy to modulate energy homeostasis, with potential ability to assist in managing metabolic diseases due to their adaptability.
This article was published in the following journal.
Name: American journal of physiology. Endocrinology and metabolism
Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insul...
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An ester of TESTOSTERONE with a propionate substitution at the 17-beta position.
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