Page 98 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 5
Pre- and postprandial energy expenditure. Baseline REE per kilogram body weight was slightly less in the control setting (–gDCA: 21.0 ± [2.51] vs. +gDCA: 21.7 ± [2.7] kcal·kg-1·day-1; P < 0.05), whereas total REE at baseline was not different between the groups (-gDCA: 1655.0 [244.5] vs. +gDCA: 1720.0 [164.0] kcal·kg-1·day-1; P > 0.05). Total energy expenditure (REE) and REE per kilogram body weight increased 90 min after meal ingestion (REE –gDCA: 1,899.0 [130.0] vs. + gDCA: 2,057.5 [483.3] kcal·kg-1·day-1; P > 0.05; REE per kilogram body weight –gDCA: 24.1 [4.2] vs. +gDCA: 26.1 [4.7] kcal·kg-1·day-1; P > 0.05) and leveled off again after 240 min (REE -gDCA: 1605.0 [301.8] kcal·kg-1·day-1 vs. +gDCA: 1,750.5 [228.8] kcal·kg-1·day-1; P > 0.05; REE per kilogram body weight –gDCA: 20.6 [3.1] kcal·kg-1·day-1 vs. +gDCA: 22.0 [3.6] kcal·kg-1·day-1, P > 0.05). However, gDCA did not alter the postprandial response of REE. Furthermore, we did not find effects of gDCA supplementation on oxidation of individual macronutrients (data not shown).
Discussion
BAs and their targets GLP-1 and FGF19 have received interest as hormone- like mediators that modulate energy metabolism. Here we explored these axes in response to 40 h fasting-induced insulin resistance and by administering oral gDCA. In the first experiment, we assessed the effects of a 40-h fast on BA metabolism because this induces insulin resistance (42) and BA metabolism is altered in various models of insulin resistance (5, 14, 47). More specifically, CA synthesis is increased and the DCA pool is relatively enlarged in patients with type 2 diabetes (5), most likely leading to the observed increased postprandial BA peaks (43, 47). Postprandial BA concentrations in plasma are suppressed in subjects with obesity (14).
We reproduced the effects of 40 h fasting on insulin sensitivity from Horton and Hill al. (19), but we found no effects of 40 h fasting on postprandial BA concentrations. Obviously, there are important differences between fasting- induced insulin resistance and the metabolic changes seen in obesity and type 2 diabetes (42). It was shown previously that insulin resistance affects the BA pool composition via upregulation of CYP8B1 (12α-hydroxylase, engaged in synthesis of CA) by diminished FoxO1 inhibition (16, 17, 20). Here we found no differences in the ratio of 12α-hydroxylated and non-12α-hydroxylated bile acids, which may
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