Fat augments leptin-induced uterine contractions by decreasing JAK2 and BKCa channel expressions in late pregnant rats. (September 2022)

• Record Type: Journal Article
• Authors: Pavithra, S.; Kishor Kumar, D.G.; Ramesh, G.; Panigrahi, Manjit; Sahoo, Monalisa; Singh, Thakur Uttam; Madhu, C.L.; Manickam, Kesavan; Shyamkumar, T.S.; Kumar, Dinesh; Parida, Subhashree
• Is Part Of: Cytokine. Volume 157(2022)
• Publication Date: 2022-09
• Subjects: BKCa channel -- High-fat diet -- JAK-2 -- Leptin -- Leptin receptor -- Uterus; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2022.155966
• Languages: English
• ISSNs: 1043-4666

Abstract

Abstract: Altered lipid metabolism in obesity causes pregnancy complications in humans and animals. Leptin levels increase in pregnancy, as well as obesity. However, the effect of obesity on uterine leptin receptors and its distal signaling is not clear. The present study aimed to understand the effect of increased fat on leptin signaling in rat uterus. Wistar female rats were fed with an HF diet (40% Fat, 17% Sucrose, 1.25% Cholesterol, 0.75% Cholic acid) for 6 weeks before the mating and during pregnancy. HF diet significantly increased the fat depots, liver weight, serum, and tissue cholesterol levels. It produced fatty degeneration in the liver and caused infiltration of inflammatory cells, cystic endometrial glands, and sub endometrial fibrosis of the uterus. In isometric tension experiments, leptin caused a significant increase in uterine contractions in high fat-fed animals compared to control animals. Analysis of receptor expressions revealed no significant difference between the groups. However, a significant decrease in the JAK2 and BKCaα mRNA expression was observed in the uterus of high fat-fed rats. No change in the BKCaβ, eNOS, iNOS, MLCP, and MLCK mRNA expressions was noticed in the HF group compared to the control. The findings of the present study suggest that the contractile response to leptin in the uterus of high fat-fed rats may be attributed to reduced signaling through JAK2 and, lowered expressions of BKCa channel α subunits.