Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

Abstract

Background/AimsAdipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH.MethodsPolymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps.ResultsPatients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05).ConclusionsNASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

Serum adipocyte fatty acid‐binding protein levels are associated with peripheral arterial disease in women, but not men, with type 2 diabetes mellitus

“…The sex difference is possibly explained by the higher body fat percentage or subcutaneous adipose tissue in women compared with men. Adipose tissue is a major source of circulating A‐FABP, and A‐FABP expression is also higher in subcutaneous fat than in visceral fat . In the present study, A‐FABP levels were significantly higher in women with PAD than those without PAD.…”

Metabolically Protective Cytokines Adiponectin and Fibroblast Growth Factor-21 Are Increased by Acute Overfeeding in Healthy Humans

“…Serum levels of FABP4 are elevated in obesity and metabolic syndrome and may contribute to development of nonalcoholic steatohepatitis (NASH) [38]. We also observed relationships between serum FABP4 and numerous measures of adiposity and insulin resistance at baseline.…”

Eicosanoids in Metabolic Syndrome

“…In human patients with NASH, visceral adipose A-FABP levels are significantly higher than in subcutaneous adipose tissue, suggesting that either A-FABP from infiltrating macrophages or visceral adipocytes predisposes patients to progress from NAFLD to NASH. In patients with NAFLD, the level of L-FABP strongly correlates with the extent of obesity and levels of hepatic lipid accumulation (Yoon et al, 2012). The prevention of liver damage in mice fed an HF diet and administered LPS to induce acute liver injury by treatment with an A-FABP inhibitor suggests that targeting the adipocyte-monocyte A-FABP may be a novel therapy to prevent NAFLD progression to NASH (Higuchi et al, 2011).…”