Mondal Samrita, Rathor Richa, Singh Som Nath, Suryakumar Geetha
Defence Institute of Physiology and Allied Sciences, Delhi, India.
Pharmacol Res Perspect. 2024 Aug;12(4):e1248. doi: 10.1002/prp2.1248.
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.
对代谢过程失调的日益关注源于环境与营养之间的复杂相互作用,这种相互作用对个体的遗传学和表观遗传学有重大影响。因此,由于营养不良、超重、生活方式改变以及暴露于热应激(HS)、冷应激或高海拔(HA)等极端环境中,食物摄入调节激素水平的任何异常都可能导致任何年龄组代谢疾病的发生。瘦素、脂联素、胃饥饿素和胆囊收缩素等激素调节食欲和饱腹感以维持能量平衡。瘦素作为一种脂肪因子和多效性激素,在调节食物摄入、能量获取和能量消耗方面发挥着主要作用。通过计算机模拟方法,我们确定了在瘦素信号通路中起关键作用的主要基因(LEP、LEPR、JAK2、STAT3、NPY、POMC、IRS1、SOCS3)。此外,从TargetScan 8.0数据库中筛选出了八个共同靶向这些基因的miRNA(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)。这些miRNA的作用值得探索,因为它们可能在调节食欲、能量代谢、代谢疾病(肥胖、2型糖尿病、心血管疾病、炎症)以及应对极端环境方面发挥重要作用。调节瘦素信号和食欲的miRNA可能有助于开发治疗代谢疾病的新疗法。