The influence of obesity, non-alcoholic steatohepatitis and bariatric surgery on plasma lipid profile

the most common liver disease in the world; its prevalence has increased recently, accompanied by global obesity pandemic. It is a complex entity that arises from numerous genetic, environmental, behavioral and social factors. Non-alcoholic steatohepatitis (NASH) is part of the disease progression and is a preamble to more severe complications such as cirrhosis and hepatocellular carcinoma. Currently, the only tool to diagnose NASH is liver biopsy. The aim is to identify the different microRNAs (miRNAs) involved in NAFLD progression. Method: 117 patientswere recruited; liver biopsy and a blood sample were obtained; 30were submitted tomicroarray assays and classified according to controlled attenuation parameter (CAP) and NAFLD activity score (NAS). Patients with CAP≤ 232 dB/m, 0-point NAS and histopathological report without alterations, were the control group; with CAP≥ 290 dB/m, NAS with 1 to 3 points and histopathological report with steatosis inmore than 5% of hepatocytes, were the NAFLD group, and patients with CAP ≥290 dB/m, NAS ≥5 points and histopathological report with steatosis accompanied by inflammatory ballooning and infiltration, were the NASH group. From blood samples, liver function tests, as well as fasting cholesterol, triglycerides, and glucose levels, were determined. RNA was extracted from liver tissue to analyze the miRNAs differential expression using the GeneChip miRNA 4.0 microarray; expression levels were compared with the Affymetrix TAC software using a fold change parameter ≥2 and ≤−2; FDR≤ 0.05 and p≤ 0.001. Results: Regarding the anthropometric characteristics, BMI had a statistical difference between control 27.8 kg/m, NAFLD 29.1 kg/m and NASH 39.1 kg/m p≤ 0.0001; liver function profile, circulating lipids and fasting glucose did not change. The microarray analysis revealed a differential expression of 24 miRNAs in the NAFLD group, 23 were upregulated and 1 downregulated; miR-122-3p was expressed 9 times more than the control, followed by the miR-1405p that showed almost 6 times more expression, the miR-200a-3p was 5 times more expressed, but also the miR-148b-3p and the miR148a-5p were 4 times more expressed than the control; while the miR-6089-2 shows 2-fold drop expression compared to the control group. While NASH results disclosed 21 differentially expressed miRNAs compared to controls, miR-297, miR-3064-5p, miR3148 and miR-7844-5p showed more than 20 times decrease expression compared to the control group. Conclusion: The results suggest that miRNAs differential expression could be used as potential NAFLD diagnostic and progression biomarkers; however, the mechanism by which these miRNAs are involved in the pathogenesis needs further investigation.