Liver fatty acid binding protein gene ablation enhances age-dependent weight gain in male mice.
Although studies performed in vitro and with transfected cells in culture suggest a role for liver fatty acid binding protein (L-FABP) in regulating fatty acid oxidation and fat deposition, the physiological significance of this possibility is not completely clear. To begin to address this question, the effect of L-FABP gene ablation on phenotype of standard rodent chow-fed male mice was examined with increasing age up to 18 months. While young (2-3 months old) L-FABP null mice displayed no visually obvious phenotype, with increasing age >9 months the L-FABP null mice were visibly larger, exhibiting increased body weight due to increased fat and lean tissue mass. Liver lipid concentrations were unaffected by L-FABP gene ablation with the exception of triacylglycerol, which was decreased by 74% in the livers of 3-month-old mice. Likewise, serum lipid levels were not altered in L-FABP null mice with the exception of triacylglycerol, which was increased in the serum of 18-month-old mice. Increased body weight, fat tissue mass, and lean tissue mass in 18-month-old L-FABP null mice were accompanied by increased hepatic levels of low-density lipoprotein (LDL) receptor, peroxisome proliferator-activated receptor (PPAR) alpha, and PPARalpha-regulated proteins such as fatty acid transport protein (FATP), fatty acid translocase (FAT/CD36), carnitine palmitoyl transferase I (CPT I), and lipoprotein lipase (LPL). A key enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase, was down-regulated in L-FABP null mice. These findings were consistent with a proposed role for L-FABP as an important physiological regulator of PPARalpha.
Martin
Gregory G
GG
Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843-4466, USA. gmartin@cvm.tamu.edu
Atshaves
Barbara P
BP
McIntosh
Avery L
AL
Payne
H Ross
HR
Mackie
John T
JT
Kier
Ann B
AB
Schroeder
Friedhelm
F
D000367:Age Factors; D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D047493:PPAR alpha / Q000235:genetics*; D015430:Weight Gain
D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D047493:PPAR alpha