Molecular basis of non-alcoholic fatty liver disease and metabolic syndrome in a subset of South Asians

Background: Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are emerging threats in Pakistan. The prevalence of MetS is reported to be 18–46% in general population. Adipokines and their genetic polymorphisms are now considered as risk factors for these conditions. Chemerin modulates glucose and lipid homeostasis, nesfatin-1 acts as an anorexigenic peptide, desnutrin regulates adipose tissue fatty acid oxidation, adipocyte fat content, and size. Therefore, this study was designed to identify the molecular and genetic differences in the above-mentioned biomarkers in metabolic syndrome positive and negative individuals. Methods: This cross-sectional study was carried out at the Aga Khan University during October 2018 till August 2019. MetS positive (n = 92) versus negative (n = 208) adults aged between 18 and 50 years of age were recruited. MetS was diagnosed on the basis of National Cholesterol Education Program Adult Control Panel III criteria. Serum adipokine levels, lipid profile, blood glucose, and insulin were measured. Fatty liver was detected by ultra-sonographic scans. Chemerin rs17173608 polymorphism was determined by tetra-arm polymerase chain reaction. Results: Higher chemerin (37.87 ± 13.60 vs. 24.03 ± 12.32 pg/ml), low desnutrin (103.08 ± 5.84;270.19 ± 25.67 pg/ml), and nesfatin levels (276.49 ± 31.09; 754.34 ± 57.77 pg/ml) were seen in Mets/NAFLD positive versus negative individuals, respectively. Serum chemerin showed a moderate positive correlation with MetS and fatty liver while desnutrin showed weak correlation with MetS, whereas nesfatin showed a moderate correlation with MetS and fatty liver (p < 0.05). Each unit increases in chemerin, and decrease in desnutrin was associated with higher odds of developing NAFLD (p < 0.05). The variant rs17173608 showed association with MetS phenotype (1.841 (1.101–3.078); p = 0.020). Presence of the minor “G” allele was seen to increase the risk of developing MetS by 1.567 (p < 0.012). Conclusion: High chemerin and low desnutrin are linked to fatty liver changes and MetS in a subset of local population. The presence of chemerin “G” allele increases the risk of developing MetS even further in the same individuals. Further studies are required for an in-depth analysis of the mechanism through which these biomarkers cause the effect.