English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Sirtuin 1 (Sirt1) is an NAD + -dependent protein deacetylase that is proposed to mediate many health-promoting effects of calorie restriction (CR). We recently reported that short-term CR increased the bile acid (BA) pool size in mice, likely due to increased BA synthesis in liver. Given the important role of Sirt1 in the regulation of glucose, lipid, as well as BA metabolism, we hypothesized that the CR-induced increase in BAs is Sirt1-dependent. To address this, the present study utilized genetically-modified mice that were Sirt1 loss of function (liver knockout, LKO) or Sirt1 gain of function (whole body-transgenic, TG). Three genotypes of mice (Sirt1-LKO, wild-type, and Sirt1-TG) were each randomly divided into  ad libitum  or 40% CR feeding for one month. BAs were extracted from various compartments of the enterohepatic circulation, followed by BA profiling by UPLC-MS/MS. CR increased the BA pool size and total BAs in serum, gallbladder, and small intestine. The CR-induced increase in BA pool size correlated with the tendency of increase in the expression of the rate-limiting BA-synthetic enzyme Cyp7a1. However, in contrast to the hypothesis, the CR-induced increase in BA pool size and Cyp7a1 expression was still observed with ablated expression of Sirt1 in liver, and completely suppressed with whole-body overexpression of Sirt1. Furthermore, in terms of BA composition, CR increased the ratio of 12α-hydroxylated BAs regardless of Sirt1 genotypes. In conclusion, the CR-induced alterations in BA pool size, BA profiles, and expression of BA-related genes do not appear to be dependent on Sirt1.

The Role of Sirt1 in Bile Acid Regulation during Calorie Restriction in Mice