Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease, Hepatic Fibrosis, and Insulin Resistance in Mice.

Sergio Quesada-Vázquez,Marina Colom-Pellicer,Antoni Caimari,Gerard Aragonès,Josep M Del Bas,Èlia Navarro-Masip,Xavier Escoté

doi:10.3390/nu13103532

Sergio Quesada-Vázquez, Marina Colom-Pellicer + Show 5 more

Open Access

https://doi.org/10.3390/nu13103532

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Abstract

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient; MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.

Highlights

This study is the first to use a combination of cofactors composed of n-acetyl cysteine (NAC), nicotinamide riboside (NR), betaine, and LC as a possible dietary strategy to treat Non-alcoholic fatty liver disease (NAFLD) development in an animal model due to its implication in different metabolic pathways that are pathologically affected in this disease
Data from the present study suggest that 4-week supplementation with this specific combination of bioactive cofactors, at intended human clinical doses, ameliorates NAFLD features in mice
These improvements involved a reduction in liver weight, hepatic steatosis, inflammation, fibrosis and partially improved insulin sensitivity

Summary

Introduction

Have emerged as the leading causes of chronic liver ailments worldwide, with a prevalence rising in most developed countries [1]. The prevalence is lower in Eastern countries, but a rising tendency has been recently observed due to the changes in dietary habits, together with the sedentary lifestyle associated with Westernized societies [1]. These Western dietary habits are characterized by a predominant and excessive intake of saturated fats and caloric oversupply that, together with an impoverishment of lifestyle, are the key causes of developing NAFLD/NASH [3]

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