Abstract
Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.
Highlights
A novel and unexpected role for bile acids (BA) in the regulation of energy metabolism has been reported in mice [1]: addition of the primary BA cholic acid (CA) to a high fat diet prevented body weight gain by increasing energy expenditure and fat oxidation [1]
Total plasma BA tended to be lower in type 2 diabetes mellitus (T2DM) due to reduced CA and significantly decreased chenodeoxycholic acid (CDCA) levels (-33%, p < 0.05; figure 2)
BA sequestrants reduce the flux of BA from the intestine to the liver, thereby reducing plasma BA concentrations, which we hypothesized would translate into changes in energy metabolism
Summary
A novel and unexpected role for bile acids (BA) in the regulation of energy metabolism has been reported in mice [1]: addition of the primary BA cholic acid (CA) to a high fat diet prevented body weight gain by increasing energy expenditure and fat oxidation [1]. This effect was explained by plasma BA raising intracellularly active thyroid hormone levels via a G-proteincoupled receptor (Gpbar1/Tgr5)-mediated activation of type 2 iodothyronine deiodinase (D2) in brown adipose tissue [1].
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