Decreased body weight and hepatic steatosis with altered fatty acid ethanolamide metabolism in aged L-Fabp mice

Abstract

This article is available online at http://www.jlr.org dramatically in the past 20 years, in parallel with the epidemic of obesity. Although environmental factors (caloric excess) and lifestyle choices (lack of exercise) are the primary causes, genetic susceptibility also predisposes individuals to obesity and its metabolic complications. Studies have identifi ed mechanisms by which food consumption is regulated, including release of factors produced within the gastrointestinal tract (CCK, ghrelin, PYY, lipid amides, and palmitoleic acid) that mediate satiety either locally or centrally ( 1 ).Recent studies have identifi ed several lipid messengers that regulate feeding behavior ( 2-5 ). These include the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (endogenous ligands of the cannabinoid receptors); the fatty acid ethanolamides (FAE), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA); and their biosynthetic precursors, the N -acyl-phosphatidylethanolamines ( 6, 7 ). OEA is an ubiquitous lipid molecule that is synthesized in the proximal small intestine following consumption of dietary fat, and it promotes satiety by binding nuclear peroxisome proliferator-activated receptor-␣ (PPAR ␣ ) and activating vagal efferents ( 8-10 ). Conversely, AEA promotes food consumption through activation of CB 1 cannabinoid receptors both in the brain and peripheral tissues. In addition, AEA regulates systemic energy utilization, infl ammation, apoptosis, and pain ( 11, 12 ). Details of how the balance between opposing satiety and orexigenic factors is maintained are a focus of investigation, but there is increasing evidence for a role of intracellular The prevalence of nonalcoholic fatty liver disease, type II diabetes, and the metabolic syndrome has increased

Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism

“…1D ). Consistent with previous fi ndings, hepatic TG content was signifi cantly lower in L-FABP KO mice compared with WT controls ( 21 ). Neither ATGL knockdown or L-FABP ablation affected the content of liver free FAs in either genotype ( Fig.…”

“…Its high expression level and ability to interact with mitochondria and nuclear transcription factors suggest that it may act as a FA sensor that alters metabolism directly via changes in intracellular FA handling as well as transcriptional regulation of metabolic pathways. To date, most studies have focused on the role of L-FABP in modulating exogenous FA metabolism, especially during fasting, high fat feeding, or in various disease models ( 20,21,25,27,28 ). The effects of L-FABP on the metabolism and signaling properties of endogenous FAs, such as those derived from lipolysis, are unknown.…”

“…ATGL shRNA administration suppressed protein expression of hepatic ATGL in both WT and L-FABP KO mice effi ciently 7 days that manipulating L-FABP expression alters PPAR-␣ -dependent transcription of genes coding for FA oxidative enzymes ( 17,18 ). Yet, studies performed in vivo are inconsistent in regard to the role of L-FABP in mediating PPAR-␣ activity, with some studies showing that PPAR-␣ target gene expression is regulated independently from L-FABP ( 16,19 ) and others showing dependence on L-FABP ( 20,21 ).…”

Recent insights into the biological functions of liver fatty acid binding protein 1

“…Ϫ / Ϫ -GFP mice fed high-fat diet showed less body weight gain and low risk of hepatic steatosis (115)(116)(117)(118)(119). Two recent review articles expressed opposing views about whether FABP1 may play an important role in preventing diet-induced obesity and/or steatosis ( 42,120 ).…”

Changes in FABP1 and gastrin receptor expression in the testes of rats that have undergone electrical injury

“…The FABP1 gene is highly transcribed in liver-derived cells, and regulated predominantly by liver-enriched transcription factors HNF3β and C/EBPα (23). A role of L-FABP in the attenuation of hepatic steatosis has also been demonstrated (24). SCP-2 expression has also been indicated to play a significant role in high density lipoprotein-mediated cholesterol efflux by regulating the size of rapid versus slow cholesterol efflux pools and/or eliciting the concomitant upregulation of L-FABP in cultured primary hepatocytes (25).…”