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

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.

Increased Expression of MiRNA-1 Contributes to Hypobaric Hypoxia-Induced Skeletal Muscle Loss.

The present study aims to analyze the role of microRNA-1 in the regulation of skeletal muscle loss under hypobaric hypoxia (HH). Male Sprague Dawley rats (n = 10) weighing 230-250 g are divided into two groups, control and HH exposure for 7 days at 25 000 ft. After the hypoxia exposure, the animals are sacrificed and hindlimb skeletal muscles are excised for further analysis. Studies found the potential role of miR-1 (myomiR) as a biomarker under different atrophic conditions. Prolonged exposure to HH leads to enhanced expression of miR-1 in skeletal muscle as compared to unexposed controls. The Bioinformatics approach is used to identify the validated targets and the biological processes of miR-1. The target prediction tools identify PAX3 and HSP70 as major targets for miR-1. Exposure to HH significantly reduces PAX3 and HSP70 expression during 7 days of HH exposure, which further enhances the activity of FOXO3, MSTN, and ATROGIN known for the progression of skeletal muscle atrophy in relation to control rats. This study indicates the increased expressions of miR-1 and reduced expression of PAX3 and HSP70 lead to impaired myogenesis in skeletal muscle under HH. Further, enhanced expression of muscle degradation genes such as FOXO3, MSTN, and ATROGIN under HH exposure causes skeletal muscle protein loss.