Abstract |
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.
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Authors | Barbara P Atshaves, Gregory G Martin, Heather A Hostetler, Avery L McIntosh, Ann B Kier, Friedhelm Schroeder |
Journal | The Journal of nutritional biochemistry
(J Nutr Biochem)
Vol. 21
Issue 11
Pg. 1015-32
(Nov 2010)
ISSN: 1873-4847 [Electronic] United States |
PMID | 20537520
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
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Copyright | Copyright © 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Fatty Acid-Binding Proteins
- Fatty Acids
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Topics |
- Animals
- Cells, Cultured
- Diet
- Fatty Acid-Binding Proteins
(genetics, metabolism)
- Fatty Acids
(metabolism)
- Female
- Hepatocytes
(metabolism)
- Lipid Metabolism
(genetics)
- Male
- Mice
- Mice, Inbred C57BL
- Mitochondria
(metabolism)
- Models, Biological
- Obesity
(genetics, metabolism)
- Peroxisomes
(metabolism)
- Rats
- Weight Gain
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