A high-fat diet is not enough to cause fatty liver disease in the short term. However, if this diet is associated with the intake of drinks sweetened with liquid fructose, the accumulation of fat in the liver accelerates and hypertriglyceridemia, a cardiovascular risk factor, may appear.
This is explained in a study on an experimental mouse model, published in the journal Molecular nutrition and food research and led by Professor Juan Carlos Laguna, from the Faculty of Pharmacy and Food Sciences, the Institute of Biomedicine of the University of Barcelona (IBUB) and the Center for Biomedical Research in Pathophysiology of Obesity and Nutrition (CIBEROBN).
The study has the collaboration of researchers Aleix Sala-Vila and Iolanda Lázaro, from the Medical Research Institute of Hospital del Mar (IMIM), and José Rodríguez-Morató, from IMIM-Hospital del Mar and MELIS-Pompeu Fabra University, among other experts.
Fructose and lipid metabolism
Fructose is one of the most common sweeteners in the food industry. This simple sugar (monosaccharide) is obtained industrially from corn syrup, a product derived from this grass. With great sweetening power and low production costs, fructose is used by the food industry to sweeten drinks, sauces and processed foods, despite scientific evidence linking it to metabolic diseases which are risk factors. of cardiovascular pathologies.
According to the new study, the effect caused by fructose in increasing the synthesis of fatty acids in the liver is more decisive than the external introduction of fats through food. “In high-fat diets that are supplemented with liquid fructose, this monosaccharide is able to induce an increase in de novo lipogenesis – that is, the formation of fat from sugar – and an inhibition of lipid oxidation in the liver,” says Professor Juan Carlos Laguna, from the Department of Pharmacology, Toxicology and Medicinal Chemistry.
“In particular, fructose intake directly affects the expression and activity of nuclear factor ChREBP. Once activated, this factor causes an increase in the expression of enzymes that control the hepatic synthesis of fatty acids,” he continues. “At the same time, fructose intake reduces the activity of the nuclear receptor PPARalfa, which is primarily responsible for controlling the expression of genes that encode enzymes involved in fatty acid oxidation (mitochondria and peroxisomes) in the liver. . »
As indicated in the preclinical study, the combination of saturated fats from food and the induction of endogenous fatty acid synthesis is at the origin of the appearance of hepatic steatosis. “In addition, we describe for the first time that fructose – unlike high fat diets – increases the expression of the PNPLA3 protein, associated with the appearance of hypertriglyceridemia, a risk factor for cardiovascular disease”, notes Núria Roglans, co-author of the study and member of the mentioned department.
fatty liver disease in men
Several epidemiological studies have linked the consumption of fructose-sweetened beverages to non-alcoholic fatty liver disease (NAFLD), a condition for which there is no specific pharmacological treatment. In these patients, de novo lipogenesis contributes up to 30% of the lipids accumulated in the liver, whereas in healthy people, this synthesis contributes only 5% of the hepatic lipids.
The animal model characterized by the team will be of potential interest for studying future drugs to treat non-alcoholic fatty liver disease (NAFLD). “People with this pathology have a higher endogenous lipid synthesis in the liver than healthy people. Therefore, the effects described in this study might also appear in humans,” the experts note.
“Unfortunately, they continue, hepatic steatosis is the starting point for more serious pathologies, such as steatohepatitis and cirrhosis. It is a practically asymptomatic pathology, although in some cases nonspecific benign digestive disorders may appear. Apart from following a healthy diet and physical activity, there is currently no effective treatment for this pathology. »
The effects described in the study are only observable if fructose is taken in its liquid form. “With regard to sugary drinks, fructose is rapidly absorbed and massively reaches the liver, producing the metabolic alterations described. To find a comparison, we might speak of the appearance of an overdose of fructose when it is taken in sugary drinks,” the team notes.
“However, when we eat fruit, the amount of fructose consumed is much lower compared to a sugary drink. In addition, the chewing process and the presence of other elements in the fruit, such as fiber, slow down the absorption of fructose. and its arrival in the liver”, conclude the authors.
