miRNA and leptin signaling in metabolic diseases and at extreme environments

Abstract

The burden of growing concern about the dysregulation of metabolic processes arises due to complex interplay between environment and nutrition that has great impact on genetics and epigenetics of an individual. Thereby, any abnormality at the level of food intake regulating hormones may contribute to the development of metabolic diseases in any age group due to malnutrition, overweight, changing lifestyle, and exposure to extreme environments such as heat stress (HS), cold stress, or high altitude (HA). Hormones such as leptin, adiponectin, ghrelin, and cholecystokinin regulate appetite and satiety to maintain energy homeostasis. Leptin, an adipokine and a pleiotropic hormone, play major role in regulating the food intake, energy gain and energy expenditure. Using in silico approach, we have identified the major genes (LEP, LEPR, JAK2, STAT3, NPY, POMC, IRS1, SOCS3) that play crucial role in leptin signaling pathway. Further, eight miRNAs (hsa-miR-204-5p, hsa-miR-211-5p, hsa-miR-30, hsa-miR-3163, hsa-miR-33a-3p, hsa-miR-548, hsa-miR-561-3p, hsa-miR-7856-5p) from TargetScan 8.0 database were screened out that commonly target these genes. The role of these miRNAs should be explored as they might play vital role in regulating the appetite, energy metabolism, metabolic diseases (obesity, type 2 diabetes, cardiovascular diseases, inflammation), and to combat extreme environments. The miRNAs regulating leptin signaling and appetite may be useful for developing novel therapeutics for metabolic diseases.

Keywords: appetite; high altitude; leptin; metabolic diseases; microRNA.

FIGURE 1

Crosstalk among organs for food intake regulation ( represents inhibition; and represents stimulation).

FIGURE 2

Adipocytokine signaling pathway regulating food intake and energy expenditure.

FIGURE 3

The network analysis of major proteins involved in leptin signaling in Homo sapiens using STRING 12.0 version.

FIGURE 4

Major genes (LEP, LEPR, AGRP, NPY, POMC, JAK2, STAT3, IRS1, SOCS3) from Leptin Signaling Pathway showed highest Fold Enrichment and –log10(FDR) in Adipocytokine Signaling Pathway out of top 20 pathways using ShinyGO 0.77.

FIGURE 5

Pathway component analysis of major genes (LEP, LEPR, AGRP, NPY, POMC, JAK2, STAT3, IRS1, SOCS3) from Leptin signaling pathway using PANTHER 18.0 database.

FIGURE 6

miRNA‐target gene network in Homo sapiens: Network vizualization of the molecular interactions between miRNAs and the major genes involved in leptin signaling using Cytoscape 3.8.2 version.

FIGURE 7

Role of leptin and miRNA signaling in metabolic diseases and at extreme environments.