TY - JOUR
T1 - Liver fatty acid binding protein (L-FABP) as a target for the prevention of high fat diet induced obesity and hepatic steatosis
AU - Newberry, Elizabeth P.
AU - Davidson, Nicholas O.
PY - 2009
Y1 - 2009
N2 - An epidemic of obesity, fueled in large part by increased consumption of diets enriched in saturated fat, has heightened interest in the pathways and mechanisms that modulate the uptake and utilization of individual dietary lipid components. Emerging evidence has implicated members of the intracellular fatty acid binding protein (FABP) multigene family as important metabolic sensors that may regulate substrate trafficking and metabolic compartmentalization. Among these, liver fatty acid binding protein (L-FABP, Fabp1) is an abundant cytosolic protein expressed in both mammalian small intestinal enterocytes and hepatocytes. L-Fabp-/ - mice were protected against hepatic steatosis following a prolonged fast, suggesting a role in modulating hepatic FA trafficking in response to augmented lipid mobilization from adipose stores. In addition, L-Fabp-/- mice are protected against obesity and hepatic steatosis when fed a high saturated fat diet or a high saturated fat diet containing cholesterol (ie Western diet), but not when fed a high fat diet containing polyunsaturated fat. These findings imply substrate specificity in the lipid sensing functions of L-FABP. Together the data suggest that L-FABP regulates elements of both intestinal and hepatic FA trafficking as well as cholesterol metabolism and in turn exerts an important role in the pathogenesis of diet- induced obesity and hepatic steatosis through specific diet-gene interactions.
AB - An epidemic of obesity, fueled in large part by increased consumption of diets enriched in saturated fat, has heightened interest in the pathways and mechanisms that modulate the uptake and utilization of individual dietary lipid components. Emerging evidence has implicated members of the intracellular fatty acid binding protein (FABP) multigene family as important metabolic sensors that may regulate substrate trafficking and metabolic compartmentalization. Among these, liver fatty acid binding protein (L-FABP, Fabp1) is an abundant cytosolic protein expressed in both mammalian small intestinal enterocytes and hepatocytes. L-Fabp-/ - mice were protected against hepatic steatosis following a prolonged fast, suggesting a role in modulating hepatic FA trafficking in response to augmented lipid mobilization from adipose stores. In addition, L-Fabp-/- mice are protected against obesity and hepatic steatosis when fed a high saturated fat diet or a high saturated fat diet containing cholesterol (ie Western diet), but not when fed a high fat diet containing polyunsaturated fat. These findings imply substrate specificity in the lipid sensing functions of L-FABP. Together the data suggest that L-FABP regulates elements of both intestinal and hepatic FA trafficking as well as cholesterol metabolism and in turn exerts an important role in the pathogenesis of diet- induced obesity and hepatic steatosis through specific diet-gene interactions.
KW - Diet induced obesity
KW - Fatty acid metabolism
KW - Hepatic steatosis
KW - Non-alcoholic fatty liver disease
UR - http://www.scopus.com/inward/record.url?scp=70350014829&partnerID=8YFLogxK
U2 - 10.2174/187152209788009805
DO - 10.2174/187152209788009805
M3 - Article
AN - SCOPUS:70350014829
SN - 1871-5222
VL - 9
SP - 30
EP - 37
JO - Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry
JF - Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry
IS - 1
ER -