Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2016; 22(22): 5165-5172
Published online Jun 14, 2016. doi: 10.3748/wjg.v22.i22.5165
Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers
Maria Emília L Monteiro, Analucia R Xavier, Felipe L Oliveira, Porphirio JS Filho, Vilma B Azeredo
Maria Emília L Monteiro, Department of Internal Medicine, Medicine College, Fluminense Federal University, Niterói, RJ 24030-210, Brazil
Analucia R Xavier, Department of Pathology, Medicine College, Fluminense Federal University, Niterói, RJ 24030-210, Brazil
Felipe L Oliveira, Biomedical Science Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
Porphirio JS Filho, Department of Pathology, Medicine College, Fluminense Federal University, Niterói, RJ 24030-210, Brazil
Vilma B Azeredo, Department of Nutrition and Dietitian, Nutrition College, Fluminense Federal University, Niterói, RJ 24030-210, Brazil
Author contributions: Monteiro MEL, Xavier AR, and Azeredo VB contributed equally by designing and performing the research and writing the paper; Oliveira FL and Filho PJS analyzed the data and wrote the paper.
Institutional review board statement: The study was authorized and approved by the Director of Nutrition College of Fluminense Federal University and by the professor responsible for the Experimental Nutrition Laboratory of the same institution.
Institutional animal care and use committee statement: The study received prior approval by the Institutional Review Board for Animal Research (CEUA), Fluminense Federal University, case number 648, February 27, 2015. It was designed based on the determinations of the Brazilian law for research with animals (law number 11.794, October 2008).
Conflict-of-interest statement: The authors have no conflicting interests.
Data sharing statement: The authors assign to the journal the rights to edit, publish, reproduce, distribute in printed and on-line version, and include in indexing or research bases the present work, hereby submitted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maria Emília L Monteiro, MD, MSc, Professor, Department of Internal Medicine, Medicine College, Fluminense Federal University, Rua Mario Sardinha, 46, São Francisco, Niterói, RJ 24360-007, Brasil. lhcastroguedes@terra.com.br
Telephone: +55-21-996358400
Received: January 19, 2016
Peer-review started: January 19, 2016
First decision: February 18, 2016
Revised: March 1, 2016
Accepted: March 14, 2016
Article in press: March 14, 2016
Published online: June 14, 2016
Abstract

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.

METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93M diet, and animals in the experimental group received an Atkins-based diet (59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation (SD) assuming unpaired and parametric data; we analyzed differences using the Student’s t-test. Statistical significance was set at P < 0.05.

RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. Sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.

CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

Keywords: Apoptosis, Liver injury, High-protein diet, High-fat diet, Low-carbohydrate diet

Core tip: Obesity is a serious and growing health problem. A high-protein, high-fat, and low-carbohydrate diet known as the Atkins diet has been adopted since the 1970s. Many people adhere to this diet in an attempt to lose weight, and it has recently been introduced for children with difficult-to-control seizures and elderly suffering from Alzheimer’s and Parkinson’s diseases. The benefits and effects of the Atkins diet remain unclear, especially in hepatic metabolism. Since the primary metabolic reactions involving macronutrients occur in the liver, it is essential to understand the potential hepatic lesions that can result from dietary modifications.