Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity.
OBJECTIVE
Fatty Acid Transport Protein 5 (FATP5) is a liver-specific member of the FATP/Slc27 family, which has been shown to exhibit both fatty acid transport and bile acid-CoA ligase activity in vitro. Here, we investigate its role in bile acid metabolism and body weight homeostasis in vivo by using a novel FATP5 knockout mouse model.


METHODS
Bile acid composition was analyzed by mass spectroscopy. Body weight, food intake, energy expenditure, and fat absorption were determined in animals fed either a low- or a high-fat diet.


RESULTS
Although total bile acid concentrations were unchanged in bile, liver, urine, and feces of FATP5 knockout mice, the majority of gallbladder bile acids was unconjugated, and only a small percentage was conjugated. Primary, but not secondary, bile acids were detected among the remaining conjugated forms in FATP5 deletion mice, suggesting a specific requirement for FATP5 in reconjugation of bile acids during the enterohepatic recirculation. Fat absorption in FATP5 deletion mice was largely normal, and only a small increase in fecal fat was observed on a high-fat diet. Despite normal fat absorption, FATP5 deletion mice failed to gain weight on a high-fat diet because of both decreased food intake and increased energy expenditure.


CONCLUSIONS
Our findings reveal an important role for FATP5 in bile acid conjugation in vivo and an unexpected function in body weight homeostasis, which will require further analysis. FATP5 deletion mice provide a new model to study the intersection of bile acid metabolism, lipid metabolism, and body weight regulation.
Hubbard
Brian
B
Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02140, USA.
Doege
Holger
H
Punreddy
Sandhya
S
Wu
Hui
H
Huang
Xueming
X
Kaushik
Virendar K
VK
Mozell
Robin L
RL
Byrnes
John J
JJ
Stricker-Krongrad
Alain
A
Chou
Chieh J
CJ
Tartaglia
Louis A
LA
Lodish
Harvey F
HF
Stahl
Andreas
A
Gimeno
Ruth E
RE
D000042:Absorption; D000375:Aging / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004435:Eating; D004734:Energy Metabolism; D050612:Fatty Acid Transport Proteins / Q000172:deficiency*; D005704:Gallbladder / Q000378:metabolism; D015870:Gene Expression; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*
D001647:Bile Acids and Salts; D004041:Dietary Fats; D050612:Fatty Acid Transport Proteins; C113098:Slc27a5 protein, mouse