Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease.
Prolonged use of total parenteral nutrition can lead to nonalcoholic fatty liver disease, ranging from hepatic steatosis to cirrhosis and liver failure. It has been demonstrated that omega-3 fatty acids are negative regulators of hepatic lipogenesis and that they can also modulate the inflammatory response in mice. Furthermore, they may attenuate hepatic steatosis even in leptin-deficient ob/ob mice. We hypothesized that omega-3 fatty acid supplementation may protect the liver against hepatic steatosis in a murine model of parenteral nutrition in which all animals develop steatosis and liver enzyme disturbances. For testing this hypothesis, groups of mice received a fat-free, high-carbohydrate liquid diet ad libitum for 19 d with enteral or i.v. supplementation of an omega-3 fatty acid emulsion or a standard i.v. lipid emulsion. Control mice received food alone or the fat-free, high-carbohydrate diet without lipid supplementation. Mice that received the fat-free, high-carbohydrate diet only or supplemented with a standard i.v. lipid emulsion developed severe liver damage as determined by histology and magnetic resonance spectroscopy as well as elevation of serum liver function tests. Animals that received an i.v. omega-3 fatty acid emulsion, however, showed only mild deposits of fat in the liver, whereas enteral omega-3 fatty acids prevented hepatic pathology and led to normalization of liver function tests. In conclusion, whereas standard i.v. lipid emulsions fail to improve dietary-induced steatotic injury to the liver, i.v. supplementation of omega-3 fatty acids partially and enteral supplementation completely protects the liver against such injury.
Alwayn
Ian P J
IP
Department of Surgery and the Vascular Biology Program, The Children's Hospital, Boston, MA 02115, USA.
Gura
Kathleen
K
Nosé
Vânia
V
Zausche
Blanca
B
Javid
Patrick
P
Garza
Jennifer
J
Verbesey
Jennifer
J
Voss
Stephan
S
Ollero
Mario
M
Andersson
Charlotte
C
Bistrian
Bruce
B
Folkman
Judah
J
Puder
Mark
M
D000818:Animals; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000627:therapeutic use; D005234:Fatty Liver / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3