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Evaluation of the relationship between weight gain, fat ectopic accumulation in the liver and hepatic expression of miR-122 in mice fed HFD for different periods

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The number of obese people worldwide is directly associated with the increased prevalence of Non-Alcoholic Fat Liver Disease (NAFLD), a disease characterized by triglycerides accumulation in the liver. Hepatic lipid metabolism may be regulated by microRNAs (miRs) expression. miR-122 is the most expressed miR in the liver and, among other functions, it regulates glucose and lipid metabolism. Insulin resistance appears to be a common event of NAFLD and obesity, since it underlies the genesis of both diseases. Therefore, the aim of the present study was to investigate a possible connection between insulin resistance, obesity, NAFLD development and alterations in miR-122 hepatic expression in mice fed with HFD for different periods. Male Swiss mice were fed with a control diet or HFD (AIN 45%) for 1, 3, 7, 15, 30 or 56 days. Body weight, adiposity and serum cholesterol were gradually increasing from HF7 to HF56. Even though there was a variation between groups, TAG levels was higher at HF1 and continued to increase until HF56, and showed a positive correlation with fasting glucose. Hepatic miR-122 expression was decreased from HF3 until HF56. In conclusion, high-fat diet consumption lead mice to hepatic miRNA modulation and metabolic disturbances that precedes changes in body composition. Changes in hepatic miR-122 expression may drive alterations in fat deposition within the liver and hyperglycemia, favoring weight gain and metabolic syndrome development.