Abstract
Ursodeoxycholic acid (UDCA) is a bile acid (BA) approved by the U.S. Food and Drug Administration for the treatment of primary biliary cholangitis. It is also the major active component of bear bile used in traditional Chinese medicine to reduce fever, remove toxins, and treat liver and eye ailments. In addition, UDCA and its conjugated form have been evaluated for their potential to improve symptoms of metabolic diseases, but the results have been inconclusive. To address this issue, in this study, we investigated the effects of orally administered UDCA on mice with diet-induced obesity, including the BA and free fatty acid (FFA) profiles of serum, liver, and epididymis and brown adipose tissues. We found that UDCA treatment significantly improved most metabolic indices; tauroursodeoxycholic acid (TUDCA) and taurolithocholic acid (TLCA) contents were increased in all examined tissues, whereas saturated FA levels were decreased, and n-3 polyunsaturated fatty acid (n-3 PUFA) levels were increased in most tissues. A correlation analysis showed that the concentrations of UDCA and its derivatives were positively correlated with that of n-3 PUFA. To clarify the mechanism by which UDCA alters FFA profiles, we analyzed the expression levels of genes involved in FFA biosynthesis, uptake, and oxidation and found that FFA biosynthesis and uptake were inhibited while FFA oxidation was stimulated by UDCA treatment. Additionally, amino acid-conjugated derivatives of UDCA, such as TUDCA and TLCA, altered FFA profiles by modulating FFA biosynthesis, uptake, and oxidation. These findings provide evidence that UDCA can alleviate metabolic dysfunction and could therefore be effective in the treatment of obesity.
Highlights
Obesity is a major risk factor for the development of type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD)
The present study evaluated the effects of orally administered Ursodeoxycholic acid (UDCA) in mice with diet-induced obesity by analyzing bile acid (BA) and free fatty acid (FFA) profiles in serum, liver, epididymis adipose tissue (EAT), and brown adipose tissue (BAT)
We compared the expression of metabolic markers in high-fat diet (HFD) mice with or without UDCA treatment to assess the effect of UDCA on obesity
Summary
Obesity is a major risk factor for the development of type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Elevated plasma free fatty acid (FFA) level is observed in obesity, which is thought to play a key role in the progression of obesity-associated. UDCA Alleviates Metabolic Dysfunction insulin resistance and CVD (Boden, 2011). Accumulating evidence suggests that bile acid (BA) plays a role in metabolic diseases and affects sensitivity to insulin, which regulates glucose levels, lipid homeostasis, and energy expenditure via activation of BA receptors in the liver, gut, and peripheral tissues (Kuipers et al, 2014; Schaap et al, 2014; Kanwal et al, 2018). Circulating BA levels are associated with NAFLD and are correlated with histological features of nonalcoholic steatohepatitis (NASH) (Puri et al, 2018). Circulating BA and FFA levels are thought to influence each other (Kim et al, 2017; Liu et al, 2017; Lu et al, 2017), the mechanism underlying this interaction is unclear
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