Previous work conducted in our laboratory suggested a role for
liver fatty acid-binding protein (L-FABP) in
obesity that develops in aging female L-FABP gene-ablated (-/-) mice. To examine this possibility in more detail, cohorts of wild-type (+/+) and L-FABP (-/-) female mice were fed a standard, low-fat, nonpurified rodent diet for up to 18 mo. Various
obesity-related parameters were examined, including
body weight and fat and lean tissue mass.
Obesity in (-/-) mice was associated with increased expression of
nuclear receptors that induce
PPARalpha (e.g.
hepatocyte nuclear factor 1alpha, genotype effect) and of
PPARalpha-regulated
proteins involved in uptake of free (
lipoprotein lipase and
fatty acid transport protein, genotype, and/or age effect) and esterified (
scavenger receptor class B type 1, genotype effect) long-chain
fatty acids (LCFA). Hepatic total
lipid and neutral
lipid levels were not affected by age or genotype, consistent with absence of gross and histologic steatosis. There was increased
mRNA expression of liver
proteins involved in LCFA oxidation [mitochondrial 3-oxoacyl-CoA thiolase (genotype effect) and
butyryl-CoA dehydrogenase (genotype and/or age effect)], increased expression of LCFA esterification
enzymes [
glycerol-3-
phosphate acyltransferase (age x genotype effect) and
acyl-CoA:cholesterol acyltransferase-2 (genotype and/or age effect)], and increased expression of
proteins involved in intracellular transfer and secretion of esterified LCFA [liver microsomal
triacylglycerol transfer
protein (genotype effect), serum
apolipoprotein (
apo) B (genotype or age effect), and liver
apoB (age and age x genotype effect)]. The data support a working model in which
obesity development in these mice results from shifts toward reduced energy expenditure and/or more efficient energy uptake in the gut.