title: Redox homeostasis and posttranslational modifications/activity of phosphatase and tensin homolog in hepatocytes from rats with diet-induced hepatosteatosis.
abstract: High-fat and high-carbohydrate diets may predispose to simple steatosis, alone or associated with necroinflammation and fibrosis (steatohepatitis). However, there are few reports about the real effect of these nutrients on hepatocyte redox homeostasis and consequent molecular derangement. Here, we investigated whether different diets would induce oxidative damage in primary rat hepatocytes and thereby affect the activity of phosphatase and tensin homolog (PTEN). We used Sprague-Dawley rats fed, for 14 weeks, a standard diet (SD), a high-fat/low-carbohydrate diet (HFD-LC), a normal-fat/high-fructose diet (NFD-HF), or a high-fat/high-fructose diet (HFD-HF). Metabolic and histological parameters were analyzed in blood and liver samples, while oxidative stress markers and related posttranscriptional modification of PTEN were analyzed in isolated hepatocytes. Our results indicate that different dietetic hypercaloric regimens caused liver damage and a significant increase of body and liver weight, as well as elevated plasma levels of alanine aminotransferase, triglycerides and insulin. Hepatocytes from NFD-HF and HFD-HF rats displayed a decrement of cell viability and proliferation rate. Hepatocytes from animals treated with hypercaloric regimens also exhibited oxidative stress greater than SD hepatocytes. Finally, NFD-HF and HFD-HF hepatocytes showed an increased PTEN phosphorylation and decreased PTEN activity, which seem strongly correlated to an increased glutathionylation of the protein. In conclusion, we demonstrate that fructose-enriched diets cause a tissue and hepatocyte damage that might exacerbate those observed in the presence of high-fat alone and might render, via redox homeostasis imbalance, the hepatocytes more prone to posttranslational modifications and activity alteration of PTEN.
authors: Unit of Metabolic and Autoimmune Liver Diseases of Bambino Gesù Children's Hospital-IRCCS, Rome, Italy. anna.alisi@opbg.net
authors: Anna
authors: A
authors: Alisi
authors: Giovannella
authors: G
authors: Bruscalupi
authors: Anna
authors: A
authors: Pastore
authors: Stefania
authors: S
authors: Petrini
authors: Nadia
authors: N
authors: Panera
authors: Mara
authors: M
authors: Massimi
authors: Giulia
authors: G
authors: Tozzi
authors: Silvia
authors: S
authors: Leoni
authors: Fiorella
authors: F
authors: Piemonte
authors: Valerio
authors: V
authors: Nobili
mesh_terms: D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D005632:Fructose / Q000009:adverse effects; D022781:Hepatocytes / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005632:Fructose; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat