Plasma bile acid levels linked to cardiometabolic risk factors in young adults

Plasma levels of bile acids (BA) appear to be dependent on sex and correlate with cardiometabolic and inflammatory risk factors in young and relatively healthy adults, according to a study.

“The findings indicate that chenodeoxycholic acid (CDCA) and glycoursodeoxycholic acid (GUDCA) levels were higher in men than in women, but these differences disappeared after adjusting for body fat percentage,” said the researchers, adding that plasma BA levels were not related to adiposity.

Overall, 136 young adults (mean age 22.1 years, 67 percent women) were included in the study. The researchers measured body composition, brown adipose tissue, serum classical cardiometabolic risk factors, and a set of eight plasma BA, including glycol-conjugated forms.

Men had higher plasma levels of CDCA and GUDCA than women, but these differences disappeared after adjusting for body fat percentage. [J Clin Endocinol Metab 2022;107:715-723]

CDCA, cholic acid (CA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA) levels showed a positive, yet weak, association with lean body mass (LBM) levels, while GDCA and glycolithocholic acid (GLCA) levels negatively correlated with ¹⁸F-fluorodeoxyglucose uptake by brown adipose tissue.

Moreover, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), and GUDCA positively correlated with glucose and insulin serum levels, homeostatic model assessment (HOMA) index, low-density lipoprotein cholesterol, tumour necrosis factor alpha, interleukin (IL)-2, and IL-8 levels, but negatively correlated with high-density lipoprotein cholesterol, ApoA1, and adiponectin levels.

These associations, however, partially vanished following the inclusion of LBM as a confounder.

“Our results reveal that plasma levels of BA (GCA and GCDCA) are related to an adverse cardiometabolic and inflammatory profiles,” the researchers said. “However, when LBM was included as a confounder, many of these associations disappeared.”

Earlier studies reported the associations of plasma CA, DCA, and CDCA levels with HOMA index and insulin levels in type 2 diabetes patients, as well as the those of plasma GCA, GDCA, and GUDCA levels with HOMA index among healthy adults. [Nutr Metab (Lond) 2011;8:48; Metabolism 2018;83:197-204]

“Additionally, it is known that BA can act as pro-inflammatory molecules when they are dysregulated and can drive the expression of pro-inflammatory genes in hepatocytes, although this phenomenon should be further investigated,” the researchers said. [Mucosal Immunol 2019;12:851-861; Am J Pathol 2011;178:175-186]

“Curiously, none of these studies investigated whether those significant correlations were independent of body composition parameters,” they noted.

In preclinical studies, BA was found to modulate insulin secretion, glucose homeostasis, and immune response via activation of the TGR5 and the farnesoid X receptor (FXR), indicating that the activation of these receptors by BA could be a potential therapy for the treatment of cardiometabolic diseases. [Best Pract Res Clin Gastroenterol 2014;28:573-583; Nature 2006;439:484-489]

“Additionally, our results suggest that the relationship of GCA and GCDCA with an adverse cardiometabolic profile could be driven by LBM,” the researchers said.

“Since skeletal muscle represents approximately 40 percent of the total body mass in humans and is linked to lower insulin resistance and expresses both FXR and TGR5 receptors, further research is needed to understand the physiological relevance of this association between plasma levels of BA and LBM,” they added. [J Clin Endocrinol Metab 2011;96:2898-2903; J Biol Chem 2018;293:10322-10332]