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      Divergent effects of resistance and endurance exercise on plasma bile acids, FGF19, and FGF21 in humans

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          Abstract

          <p class="first" id="d8469877e177"> <b>BACKGROUND.</b> Exercise has profound pleiotropic health benefits, yet the underlying mechanisms remain incompletely understood. Endocrine FGF21, bile acids (BAs), and BA-induced FGF19 have emerged as metabolic signaling molecules. Here, we investigated if dissimilar modes of exercise, resistance exercise (RE) and endurance exercise (EE), regulate plasma BAs, FGF19, and FGF21 in humans. </p><p id="d8469877e182"> <b>METHODS.</b> Ten healthy, moderately trained males were enrolled in a randomized crossover study of 1 hour of bicycling at 70% of VO <sub> <sub>2peak</sub> </sub> (EE) and 1 hour of high-volume RE. Hormones and metabolites were measured in venous blood and sampled before and after exercise and at 15, 30, 60, 90, 120, and 180 minutes after exercise. </p><p id="d8469877e193"> <b>RESULTS.</b> We observed exercise mode–specific changes in plasma concentrations of FGF19 and FGF21. Whereas FGF19 decreased following RE ( <i> <i>P</i> </i> &lt; 0.001), FGF21 increased in response to EE ( <i> <i>P</i> </i> &lt; 0.001). Total plasma BAs decreased exclusively following RE ( <i> <i>P</i> </i> &lt; 0.05), but the composition of BAs changed in response to both types of exercise. Notably, circulating levels of the potent TGR5 receptor agonist, lithocholic acid, increased with both types of exercise ( <i> <i>P</i> </i> &lt; 0.001). </p><p id="d8469877e222"> <b>CONCLUSION.</b> This study reveals divergent effects of EE and RE on circulating concentrations of the BA species, FGF19, and FGF21. We identify temporal relationships between decreased BA and FGF19 following RE and a sharp disparity in FGF21 concentrations, with EE eliciting a clear increase parallel to that of glucagon. </p><p id="d8469877e227"> <b>FUNDING.</b> The Novo Nordisk Foundation (NNF17OC0026114) and the Lundbeck Foundation (R238-2016-2859). </p><p class="first" id="d8469877e234"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/16bb576c-4d73-4862-8a89-975a7e7f7d6e/PubMedCentral/image/jciinsight-3-122737-g180.jpg"/> </div> </p><p class="first" id="d8469877e239">Endurance exercise and resistance exercise exert differential effects on plasma concentrations of FGF19 and FGF21 in a randomized crossover study. </p>

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          The bile acid TGR5 membrane receptor: from basic research to clinical application.

          The TGR5 receptor (or GP-BAR1, or M-BAR) was characterized ten years ago as the first identified G-coupled protein receptor specific for bile acids. TGR5 gene expression is widely distributed, including endocrine glands, adipocytes, muscles, immune organs, spinal cord, and the enteric nervous system. The effect of TGR5 activation depends on the tissue where it is expressed and the signalling cascade that it induces. Animal studies suggest that TGR5 activation influences energy production and thereby may be involved in obesity and diabetes. TGR5 activation also influences intestinal motility. This review provides an overview of TGR5-bile acid interactions in health as well as the possible involvement of TGR5 in human disease.
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            Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis

            During cold stimulation, cholesterol is converted to bile acids in an alternative pathway. The bile acids then alter the microbiota, which in turn promotes more heat generation.
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              Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man.

              Bile acids (BAs) traversing the enterohepatic circulation exert several important metabolic effects. Their hepatic synthesis, controlled by the enzyme cholesterol 7alpha-hydroxylase (CYP7A1), has a unique diurnal variation in man. Here we provide evidence that the transintestinal flux of BAs regulates serum levels of intestinal fibroblast growth factor 19 (FGF19) that in turn modulate BA production in human liver. Basal FGF19 levels varied by 10-fold in normal subjects, and were reduced following treatment with a BA-binding resin and increased upon feeding the BA chenodeoxycholic acid. Serum FGF19 levels exhibited a pronounced diurnal rhythm with peaks occurring 90-120 min after the postprandial rise in serum BAs. The FGF19 peaks in turn preceded the declining phase of BA synthesis. The diurnal rhythm of serum FGF19 was abolished upon fasting. We conclude that, in humans, circulating FGF19 has a diurnal rhythm controlled by the transintestinal BA flux, and that FGF19 modulates hepatic BA synthesis. Through its systemic effects, circulating FGF19 may also mediate other known BA-dependent effects on lipid and carbohydrate metabolism.
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                Author and article information

                Journal
                JCI Insight
                American Society for Clinical Investigation
                2379-3708
                August 9 2018
                August 9 2018
                August 9 2018
                August 9 2018
                : 3
                : 15
                Article
                10.1172/jci.insight.122737
                6129127
                30089729
                f0413fd2-42b2-4d44-b3e5-dab81a53a003
                © 2018
                History

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