Silvio Pires Gomes1, Andréa Almeida Pinto da Silva1, Amanda Rabello Crisma2, Primavera Borelli2, Francisco Javier Hernandez-Blazquez1, Mariana P de Melo3, Barbara Bacci4, Andrzej Loesch5, A Augusto Coppi6. 1. Laboratory of Stochastic Stereology and Chemical Anatomy (LSSCA), Department of Surgery, College of Veterinary Medicine and Animal Science, University of São Paulo (USP), São Paulo, Brazil. 2. Laboratory of Haematology, Department of Clinical and Toxicologic Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, Brazil. 3. Department of Basic and Environmental Sciences, Engineering School of Lorena, University of Sao Paulo (USP), Lorena, Brazil. 4. School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom. 5. Division of Medicine, University College London School of Life and Medical Sciences, Royal Free Campus, United Kingdom. 6. School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom. Electronic address: a.coppi@surrey.ac.uk.
Abstract
OBJECTIVE: The aim of the present study was to investigate the putative effects of a low-protein diet on the three-dimensional structure of hepatocytes and determine whether this scenario could be reversed by restoring the adequate levels of protein to the diet. METHODS: Using design-based stereology, the total number and volume of hepatocytes were estimated in the liver of mice in healthy and altered (by protein malnutrition) conditions and after protein renutrition. RESULTS: This study demonstrated a 65% decrease in the liver volume (3302 mm3 for the control for undernourished versus 1141 mm3 for the undernourished group) accompanied by a 46% reduction in the hepatocyte volume (8223 μm3 for the control for undernourished versus 4475 μm3 for the undernourished group) and a 90% increase in the total number of binucleate hepatocytes (1 549 393 for the control for undernourished versus 2 941 353 for the undernourished group). Reinstating a normoproteinic diet (12% casein) proved to be effective in restoring the size of hepatocytes, leading to an 85% increase in the total number of uninucleate hepatocytes (15 988 560 for the undernourished versus 29 600 520 for the renourished group), and partially reversed the liver atrophy. CONCLUSIONS: Awareness of these data will add to a better morphologic understanding of malnutrition-induced hepatopathies and will help clinicians improve the diagnosis and treatment of this condition in humans and in veterinary practice.
OBJECTIVE: The aim of the present study was to investigate the putative effects of a low-protein diet on the three-dimensional structure of hepatocytes and determine whether this scenario could be reversed by restoring the adequate levels of protein to the diet. METHODS: Using design-based stereology, the total number and volume of hepatocytes were estimated in the liver of mice in healthy and altered (by protein malnutrition) conditions and after protein renutrition. RESULTS: This study demonstrated a 65% decrease in the liver volume (3302 mm3 for the control for undernourished versus 1141 mm3 for the undernourished group) accompanied by a 46% reduction in the hepatocyte volume (8223 μm3 for the control for undernourished versus 4475 μm3 for the undernourished group) and a 90% increase in the total number of binucleate hepatocytes (1 549 393 for the control for undernourished versus 2 941 353 for the undernourished group). Reinstating a normoproteinic diet (12% casein) proved to be effective in restoring the size of hepatocytes, leading to an 85% increase in the total number of uninucleate hepatocytes (15 988 560 for the undernourished versus 29 600 520 for the renourished group), and partially reversed the liver atrophy. CONCLUSIONS: Awareness of these data will add to a better morphologic understanding of malnutrition-induced hepatopathies and will help clinicians improve the diagnosis and treatment of this condition in humans and in veterinary practice.