Nutritional genomics, inflammation and obesity

Abstract

The Human Genome Project has significantly broadened our understanding of the molecular aspects regulating the homeostasis and the pathophysiology of different clinical conditions. Consequently, the field of nutrition has been strongly influenced by such improvements in knowledge - especially for determining how nutrients act at the molecular level in different conditions, such as obesity, type 2 diabetes, cardiovascular disease, and cancer. In this manner, characterizing how the genome influences the diet and vice-versa provides insights about the molecular mechanisms involved in chronic inflammation-related diseases. Therefore, the present review aims to discuss the potential application of Nutritional Genomics to modulate obesity-related inflammatory responses. Arch Endocrinol Metab. 2020;64(3):205-22.

Figure 1. MicroRNA biogenesis and cellular release mechanisms. MicroRNAs (miRNA) is transcribed by RNA polymerase II from miRNA genes, first forming the ‘primary miRNA transcript’ (pri-miRNA), which is then cleaved by the DROSHA/ DiGeorge syndrome critical region 8 (DGCR8) microprocessor complex to form the ‘miRNA precursor’ (pre-miRNA). Pre-miRNA is then exported from the nucleus to the cytoplasm by exportin 5 and further processed by DICER to originate the mature miRNA. Mature miRNA is loaded into the miRNA-induced silencing complex (miRISC), which contains Argonaute (AGO) proteins, that targets mRNA by sequence complementary binding and mediates gene suppression by targeted mRNA degradation. The cellular release mechanisms include pre-miRNA or mature miRNA associated to RNA-binding proteins, such as Ago2 or their binding to high-density lipoproteins (HDL). Furthermore, pre-miRNA or mature miRNA can be incorporated into small vesicles called exosomes, which are extracellular vesicles of endosomal origin that have emerged as key mediators of intercellular communication.