The α-1-acid glycoprotein/orosomucoids (ORMs) are members of the lipocalin 
protein family. Encoded by 3 polymorphic genes in mouse (2 in man, 1 in rat), 
ORMs are expressed in hepatocytes and function as acute-phase proteins secreted 
in plasma under stressful conditions. In addition to their role of nanocarrier, 
ORMs are involved in several pathophysiological processes such as 
immunosuppression, cardioprotection, and inflammatory bowel disease. The nuclear 
bile acid receptor farnesoid X receptor (FXR) regulates bile acid homeostasis 
and lipid and glucose metabolism and is an important modulator of enterohepatic 
functions. Here we report that hepatic FXR deletion in mice affects the 
expression of several members of the lipocalin family, among which ORMs are 
identified as direct FXR target genes. Indeed, a FXR response element upstream 
of the mouse Orm1 promoter was identified to which hepatic, but not ileal, FXR 
can bind and activate ORM expression in vitro and in vivo. However, ORMs are 
regulated in a species-specific manner because the ORM cluster is regulated by 
FXR neither in human nor rat cell lines. Consistent with these data, chromatin 
immunoprecipitation sequencing analysis of the FXR genomic binding sites did not 
detect any FXR response element in the vicinity of the human or rat ORM gene 
cluster. Thus, bile acids and their cognate nuclear receptor, FXR, are 
regulators of ORM expression, with potential implications for the 
species-specific metabolic and inflammation control by FXR because the 
expression of the proinflammatory genes in epididymal white adipose tissue was 
dependent on liver FXR activation.