Liver fatty acid-binding protein and obesity.
While low levels of unesterified long chain fatty acids (LCFAs) are normal metabolic intermediates of dietary and endogenous fat, LCFAs are also potent regulators of key receptors/enzymes and at high levels become toxic detergents within the cell. Elevated levels of LCFAs are associated with diabetes, obesity and metabolic syndrome. Consequently, mammals evolved fatty acid-binding proteins (FABPs) that bind/sequester these potentially toxic free fatty acids in the cytosol and present them for rapid removal in oxidative (mitochondria, peroxisomes) or storage (endoplasmic reticulum, lipid droplets) organelles. Mammals have a large (15-member) family of FABPs with multiple members occurring within a single cell type. The first described FABP, liver-FABP (L-FABP or FABP1), is expressed in very high levels (2-5% of cytosolic protein) in liver as well as in intestine and kidney. Since L-FABP facilitates uptake and metabolism of LCFAs in vitro and in cultured cells, it was expected that abnormal function or loss of L-FABP would reduce hepatic LCFA uptake/oxidation and thereby increase LCFAs available for oxidation in muscle and/or storage in adipose. This prediction was confirmed in vitro with isolated liver slices and cultured primary hepatocytes from L-FABP gene-ablated mice. Despite unaltered food consumption when fed a control diet ad libitum, the L-FABP null mice exhibited age- and sex-dependent weight gain and increased fat tissue mass. The obese phenotype was exacerbated in L-FABP null mice pair fed a high-fat diet. Taken together with other findings, these data suggest that L-FABP could have an important role in preventing age- or diet-induced obesity.
Atshaves
Barbara P
BP
Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843-4466, USA.
Martin
Gregory G
GG
Hostetler
Heather A
HA
McIntosh
Avery L
AL
Kier
Ann B
AB
Schroeder
Friedhelm
F
D000818:Animals; D002478:Cells, Cultured; D004032:Diet; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism; D051381:Rats; D015430:Weight Gain
D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids