Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity

Area of Science:

• Biochemistry
• Metabolic Physiology
• Genetics

Background:

• Fatty Acid Transport Protein 5 (FATP5) is a liver-specific enzyme with known fatty acid transport and bile acid-CoA ligase activity in vitro.
• Its in vivo role in bile acid metabolism and body weight regulation remained largely uncharacterized.

Purpose of the Study:

• To investigate the in vivo function of FATP5 in bile acid metabolism and body weight homeostasis using a novel FATP5 knockout mouse model.

Main Methods:

• Generated FATP5 knockout mice.
• Analyzed bile acid composition using mass spectroscopy.
• Assessed body weight, food intake, energy expenditure, and fat absorption on low- and high-fat diets.

Main Results:

• FATP5 knockout mice exhibited unconjugated bile acids in gallbladder bile, indicating impaired bile acid reconjugation during enterohepatic recirculation.
• Fat absorption was largely normal, with only a minor increase in fecal fat on a high-fat diet.
• FATP5 deletion led to reduced weight gain on a high-fat diet due to decreased food intake and increased energy expenditure.

Conclusions:

• FATP5 plays a significant role in bile acid conjugation in vivo.
• FATP5 unexpectedly influences body weight homeostasis, impacting energy balance and food intake.
• FATP5 knockout mice serve as a valuable model for studying the interplay between bile acid metabolism, lipid metabolism, and weight regulation.