Intracellular Nicotinamide Phosphoribosyltransferase Protects against Hepatocyte Apoptosis and Is Down-Regulated in Nonalcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is becoming one of the world's most common chronic liver diseases in childhood, yet no therapy is available that has been approved by the food and drug administration (FDA). Previous studies have reported that telomere and telomerase are involved the development and progression of NAFLD. This study was designed to investigate the potential beneficial effects of activated carbon N-acetylcys-teine (ACNAC) microcapsules on the development of NAFLD in young rats as well as the underlying mechanism(s) involved. Three-week old male Sprague Dawley rats were given high-fat diet (HFD) with/without ACNAC treatment for 7 consecutive weeks. Liver patholo-gies were determined by hematoxylin and eosin (H&E) and Oil Red O staining, as well as by changes in biochemical parameters of plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, respectively. Glucose homeostasis was evaluated by the glucose tolerance test and the liver telomere length and activity were measured by real time PCR and telomeric repeat amplification protocol (TRAP). Western blot analysis was performed to determine the expression level of Bcl-2, Bax and Caspase-3. Our results demonstrated that ACNAC supplementation improved liver pathologies of rats that received long-term HFD feeding. ACNAC supplementation prevented HFD-induced telomere shortening and improved telomerase activity. Moreover, in comparison to HFD-fed rats, ACNAC supplementation markedly increased the expression of Bcl-2, but significantly decreased the expression of Bax and Caspase-3 in juvenile rats. Together, these results indicate that ACNAC may be a promising choice for preventing and treating NAFLD among children.

Nicotinamide Phosphoribosyltransferase Inhibitor Is a Novel Therapeutic Candidate in Murine Models of Inflammatory Lung Injury

“…Although iNAMPT and iNAMPTgenerated iNAD are associated with reduced caspase-8 and caspase-3 activities (20), the mechanism by which iNAMPT and iNAD function as inhibitors of apoptosis induced by inflammatory stimuli is poorly understood but may involve the MAPK-PI3-kinase pathway (24,25) as well as increased SIRT-1 activity leading to PARP overexpression and increased PARP activities (26). These findings indicate that iNAMPT promotes endogenous prosurvival factors.…”

Possible Role of Visfatin in Hepatoma Progression and the Effects of Branched-Chain Amino Acids on Visfatin-Induced Proliferation in Human Hepatoma Cells

“…Abnormalities in serum levels of visfatin have also been reported in nonalcoholic fatty liver disease, which is a hepatic manifestation of metabolic syndrome (13). These results are somewhat conflicting, however, as both increased and decreased serum levels of this adipocytokine have been found in patients with nonalcoholic fatty liver disease (14,15).…”

Modulation of Cell Death and Survival by Adipokines in the Liver

“…Visfatin protects hepatocytes from apoptosis and exerts hepatoprotective roles in non-alcoholic fatty liver disease (NAFLD) model. 41) Resistin, originally regarded to play a role in insulin resistance, also mediates proliferation and migration of HSCs and suppression of apoptosis via interleukin-6 (IL-6) and MCP-1 dependent mechanism in these cells. 42) 6.2.…”