Page 156 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 8
chenodeoxycholic acid was proposed to increase BAT thermogenesis in lean healthy volunteers via TGR5 stimulation.68 However, the temporary 5% increase in basal energy expenditure was not readily explained by the marginally increased BAT activity, suggesting that other bile acid signalling pathways such as FXR and its downstream hormone, fibroblast growth factor 19, might be more important than chenodeoxycholic acid.
An increase in both fasting and postprandial bile acid concentrations is well established in patients after they have undergone bariatric surgery.54,55,72,73 Whether the increase in plasma bile acid concentrations precedes the increase in energy expenditure, however, is controversial. Notably, the postprandial neuroendocrine response, consisting of hormone and bile acid release after a meal, is blunted in patients with obesity but restored after RYGB surgery.53 Werling and colleagues74 showed that both postprandial and total energy expenditure were increased in seven women with stable bodyweight 9 years after RYGB surgery, compared with women matched for anthropometric parameters who had undergone vertical sleeve gastrectomy. The effect in women who had RYGB surgery was ascribed to increased postprandial neuroendocrine response. Major limitations in these studies are the heterogeneity of patient populations (eg, sex, body composition, BMI, surgical technique) and the short timeframe in which energy expenditure measurements were done (ie, resting instead of total or postprandial energy expenditure).
In conclusion, Tgr5–Dio2-mediated thermogenesis in murine BAT suggests a promising bile acid signalling-related pharmacological target. However, quantitative and physical properties of human thermogenesis (eg, organ site and size, molecular mechanisms) restrict the clinical translation of animal studies to human beings at present.
TGR5 as a modulator of inflammatory signals
Background
With the presumed function of TGR5 as a nutrient sensor, its role in modulating inflammation is of interest. Additionally, the postprandial state is established to be proinflammatory and atherogenic. TGR5 is abundantly expressed on immune cells of the monocyte lineage, namely Kupffer cells, monocytes, macrophages, and
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