Publications

UNLABELLED

Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. We tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end, stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%.

CONCLUSION

The data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease.

BACKGROUND

Limited data are available on the effects of air travel in patients with pulmonary hypertension (PH), despite their risk of physiologic compromise. We sought to quantify the incidence and severity of hypoxemia experienced by people with PH during commercial air travel.

METHODS

We recruited 34 participants for a prospective observational study during which cabin pressure, oxygen saturation (Sp O 2 ), heart rate, and symptoms were documented serially at multiple predefined time points throughout commercial flights. Oxygen desaturation was defined as SpO2, <85%.

RESULTS

Median flight duration was 3.6 h (range, 1.0-7.3 h). Mean ± SD cabin pressure at cruising altitude was equivalent to the pressure 1,968 ± 371 m (6,456 ± 1,218 ft) above sea level (ASL)(maximum altitude 5 2,621 m [8,600 ft] ASL). Median change in Sp O 2 from sea level to cruising altitude was 2 4.9% (range, 2.0% to 2 15.8%). Nine subjects (26% [95% CI, 12%-38%]) experienced oxygen desaturation during flight (minimum Sp O 2 5 74%). Thirteen subjects (38%) reported symptoms during flight, of whom five also experienced desaturations. Oxygen desaturation was associated with cabin pressures equivalent to . 1,829 m (6,000 ft) ASL, ambulation, and flight duration(all P values , .05).

CONCLUSIONS

Hypoxemia is common among people with PH traveling by air, occurring in one in four people studied. Hypoxemia was associated with lower cabin pressures, ambulation during flight, and longer flight duration. Patients with PH who will be traveling on flights of longer duration or who have a history of oxygen use, including nocturnal use only, should be evaluated for supplemental in-flight oxygen.