Fructose and NAFLD: metabolic implications and models of induction in rats

Abstract

PURPOSE:The increase in fructose consumption is paralleled by a higher incidence of obesity worldwide. This monosaccharide is linked to metabolic syndrome, being associated with hypertriglyceridemia, hypertension, insulin resistance and diabetes mellitus. It is metabolized principally in the liver, where it can be converted into fatty acids, which are stored in the form of triglycerides leading to NAFLD. Several models of NAFLD use diets high in simple carbohydrates. Thus, this study aimed to describe the major metabolic changes caused by excessive consumption of fructose in humans and animals and to present liver abnormalities resulting from high intakes of fructose in different periods of consumption and experimental designs in Wistar rats. METHODS: Two groups of rats were fasted for 48 hours and reefed for 24 or 48 hours with a diet containing 63% fructose. Another group of rats was fed an diet with 63% fructose for 90 days. RESULTS: Refeeding for 24 hours caused accumulation of large amounts of fat, compromising 100% of the hepatocytes. The amount of liver fat in animals refed for 48 hours decreased, remaining mostly in zone 2 (medium-zonal). In liver plates of Wistar rats fed 63% fructose for 45, 60 and 90 days it's possible to see that there is an increase in hepatocytes with fat accumulation according to the increased time; hepatic steatosis, however, is mild, compromising about 20% of the hepatocytes. CONCLUSIONS: Fructose is highly lipogenic, however the induction of chronic models in NAFLD requires long periods of treatment. The acute supply for 24 or 48 hours, fasted rats can cause big changes, liver steatosis with macrovesicular in all lobular zones. Key words: Fructose. Fatty Liver. Diet. Rats. RESUMO OBJETIVO:O aumento do consumo de frutose é concomitante a maior incidência mundial de obesidade. Este monossacarídeo está relacionado à Síndrome Metabólica, sendo vinculado à hipertrigliceridemia, hipertensão arterial, resistência à insulina e diabetes mellitus. É metabolizada principalmente no fígado, onde pode ser convertida em ácidos graxos, os quais serão estocados na forma de trigligérides ocasionando a esteatose hepática não alcoólica (NAFLD). Vários modelos de NAFLD utilizam dietas ricas em carboidratos simples. Desta forma, este trabalho teve como objetivos descrever as principais alterações metabólicas causadas pelo consumo excessivo de frutose em humanos e em animais e apresentar as alterações hepáticas decorrentes da alta ingestão de frutose em diferentes períodos de consumo e desenhos experimentais em ratos Wistar. MÉTODOS: Dois grupos de ratos Wistar foram mantidos em jejum durante 48 horas e realimentados por 24 ou 48 horas com dieta contendo 63% de frutose. Outro grupo de ratos Wistar foi alimentado com 63% de frutose durante 90 dias. RESULTADOS: A realimentação por 24 horas provocou acúmulo de grande quantidade de gordura. A quantidade de gordura hepática nos animais realimentados por 48 horas diminuiu, mantendo-se principalmente nas zona 2 (medio-zonal). Em fígados de ratos Wi...

Review article: fructose in non‐alcoholic fatty liver disease

“…NAFLD is strongly associated with obesity and insulin resistance and is currently conceptualised as the hepatic manifestation of metabolic syndrome (MS) . Growing evidence suggests that the fast‐growing and alarming epidemic of NAFLD is closely intertwined with the Westernisation of dietary patterns with an increasing intake of simple sugars, especially fructose …”

“…Starting from the 1960s, a number of animal and human studies have reported associations with excessive fructose consumption and adverse metabolic effects, which may have important hepatic consequences (including the development of NAFLD). The potential role of fructose in the pathogenesis of NAFLD has thus recently gained mounting attention and has been previously reviewed in detail . However, the extent to which fructose consumption is playing a role in liver damage and failure has not yet been investigated fully.…”

“…[6][7][8] Growing evidence suggests that the fast-growing and alarming epidemic of NAFLD is closely intertwined with the Westernisation of dietary patterns with an increasing intake of simple sugars, especially fructose. [9][10][11][12][13][14] Fructose is an isomer of glucose with a hydroxyl group on carbon-4 reversed in position. 15 Recent decades have witnessed an enormous rise in fructose consumption.…”

Lactoferrin Dampens High-Fructose Corn Syrup-Induced Hepatic Manifestations of the Metabolic Syndrome in a Murine Model

“…NAFLD is a common liver disease usually occurring in patients that do not habitually consume alcohol and manifesting as an excessive accumulation of triglycerides in the liver, leading to fat build-up and an increase in total liver weight of over 5%. The prevalence of fatty liver in obese and diabetic patients can reach 70–90% [2]. Fatty liver occurs either as simple steatosis (hepatic steatosis) or in combination with non-alcoholic liver inflammation.…”

Efeito da toxina botulínica tipo A na viabilidade do retalho cutâneo dorsal em ratos saudáveis, expostos à fumaça de cigarro e diabéticos

“…A primeira opção leva cerca de 90 dias para induzir o diabete, com resultados variáveis. Já a aloxana e a estreptozocina levam 24h para a indução do diabete (Castro et al, 2011).…”