ABSTRACT
BACKGROUND/AIMS: Adipose 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. METHODS: Polymerase 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. RESULTS: Patients 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). CONCLUSIONS: NASH 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.
Subject(s)
Adult , Aged , Humans , Middle Aged , Adipose Tissue/metabolism , Fatty Acid-Binding Proteins/genetics , Fatty Liver/metabolism , Gene Expression Regulation , Intra-Abdominal Fat/metabolism , Liver/metabolism , Nicotinamide Phosphoribosyltransferase/genetics , RNA, Messenger/metabolism , Retinol-Binding Proteins, Plasma/geneticsABSTRACT
Cervical cancer is the second most common gynecological cancer among Korean women. While nationwide screening program has developed, the pathogenesis of cervical cancer is unknown. The aim of this study was to compare the protein expression profiles between cervical squamous carcinomas and normal cervical tissues in order to identify proteins that are related to the cancer. Three cervical cancer tissue samples and three normal cervical tissue samples were obtained and protein expression was compared and was identified in the samples with the use of matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 20 proteins that showed up-regulated expression in the cervical cancer tissue samples were selected and identified. Seven proteins were matched to allograft inflammatory factor 1 (AIF-1), actine-like protein 2 (ALP2), brain type fatty acid-binding protein (B-FABP), NCK adaptor protein 1 (NCK-1), islet cell autoantigen 1 (ICA69), cationic trypsinogen (PRSS1), and cyclin-dependent kinase 4 (CDK4), but the remaining 13 proteins were unidentifiable. After confirmation by RT-PCR, Western blotting and immunohistochemistry, we found that B-FABP, NCK-1, and CDK4 were related to the pathogenesis of cervical cancer. These proteins are suggested as candidates of new pathological tumor markers for cervical cancer.
Subject(s)
Female , Humans , Adaptor Proteins, Signal Transducing/genetics , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Cyclin-Dependent Kinase 4/genetics , Electrophoresis, Gel, Two-Dimensional , Fatty Acid-Binding Proteins/genetics , Immunohistochemistry , Oncogene Proteins/genetics , Proteomics , Reverse Transcriptase Polymerase Chain Reaction , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Biomarkers, Tumor/genetics , Uterine Cervical Neoplasms/metabolismABSTRACT
The genetic components of insulin-resistance, diabetes and obesity have been largely studied. These conditions are determined by multiple polygenic and environmental factors. Certain candidate genes, that have common functional variants in the general population, may be important determinants of inter-individual differences in the response to dietary changes. This review focuses in one of the major candidate genes, the gene encoding for the FABP2, an intracellular protein expressed only in the intestine, involved in the absorption and intracellular transport of dietary long chain fatty acids. Carriers of the Thr54 allele in FABP2 have a 2-fold greater affinity for long chain fatty acids than Ala54 carriers. The increased flux of dietary fatty acids (FA) into the circulation, among carriers of FABP2 Ala54Thr, supports a role of the polymorphism of this allele in the etiology of metabolic disorders. The frequencies of the polymorphism in different populations fluctuate between 18% and 40%. FABP2 Ala54Thr variant has been associated with an increased fasting insulin concentration, fasting fatty acid oxidation and reduced glucose uptake. This evidence, although not conclusive, sustains an association between FABP-2 genotype and metabolic abnormalities.