Background: Edible plants have been linked to the mitigation of metabolic disturbances in liver and adipose tissue, including the decrease of lipogenesis and the enhancement of lipolysis and adipocyte browning. In this context, plant microRNAs could be key bioactive molecules underlying the cross-kingdom beneficial effects of plants. This study sought to explore the impact of plant-derived microRNAs on the modulation of adipocyte and hepatocyte genes involved in metabolism and thermogenesis.
Methods: Plant miR6262 was selected as a candidate from miRBase for the predicted effect on the regulation of human metabolic genes. Functional validation was conducted after transfection with plant miRNA mimics in HepG2 hepatocytes exposed to free fatty acids to mimic liver steatosis and hMADs cells differentiated into brown-like adipocytes.
Results: miR6262 decreases the expression of the predicted target RXRA in the fatty acids-treated hepatocytes and in brown-like adipocytes and affects the expression profile of critical genes involved in metabolism and thermogenesis, including PPARA, G6PC, SREBF1 (hepatocytes) and CIDEA, CPT1M and PLIN1 (adipocytes). Nevertheless, plant miR6262 mimic transfections did not decrease hepatocyte lipid accumulation or stimulate adipocyte browning.
Conclusions: these findings suggest that plant miR6262 could have a cross-kingdom regulation relevance through the modulation of human genes involved in lipid and glucose metabolism and thermogenesis in adipocytes and hepatocytes.
Keywords: NAFLD; RXRA; adipose tissue; browning; cross-kingdom regulation; diet; fatty liver; metabolism; plant microRNA; steatosis.