KCNMA1, a pore‐forming α‐subunit of BK channels, regulates insulin signalling in mature adipocytes

Abstract

KCNMA1 is a pore-forming α-subunit of the large conductance Ca - and voltage-activated K channels, referred to as BK channels, which play key roles in various physiological functions. However, the role of KCNMA1 in mature adipocytes remains unclear. In this study, we reveal that kcnma1 expression is downregulated in white adipose tissue of mice fed a high-fat diet and in hypertrophied adipocytes. Furthermore, inhibition of kcnma1 expression or treatment with a BK channel blocker attenuated insulin-induced Akt phosphorylation in mature adipocytes. These results strongly indicate that KCNMA1 contributes to the regulation of insulin signalling in mature adipocytes.

Adipocyte epigenetic alterations and potential therapeutic targets in transgenerationally inherited lean and obese phenotypes following ancestral exposures

“…The most common genes identified were Caln1, Ikzf1, Iqsec3, Kcnma1, Ksr2, Mycbp2, Myo16, Negr1, Nr1h5, Rbms3, and Tmem236. The Kcnma1 gene is inhibited in obese animals being fed a high fat diet and modulates the insulin signaling pathway with a phenotype of increased fat tissue mass and decreased muscle mass [59]. Ksr2 is a gene that is highly relevant to obesity and type 2 diabetes.…”

“…An extended list of all common DMR using 2 DMR sets in common are presented in Table S9. A literature search of these overlapping genes found a high correlation to obesity, type 2 diabetes, and metabolic syndrome [58][59][60][61][62], Figure 6. Therefore, a number of adipocyte and metabolic disease related genes previously identified were associated with differentially methylated DMRs within the obese and lean phenotypes of the control and ancestrally exposed animals.…”

Knockdown of RhoE Expression Enhances TGF-β-Induced EMT (epithelial-to-mesenchymal transition) in Cervical Cancer HeLa Cells

“…Total RNA was extracted using RNAiso Plus (TaKaRa, Siga, Japan) according to the manufacturer’s instructions. Reverse transcription and qPCR were performed as previously described [49]. The specific primers for human RhoE, snail, fibronectin, and 18S rRNA were as follows: human RhoE-forward, 5′-AATAGAGTTGAGCCTGTGGG-3′; human RhoE-reverse, 5′-CTAATGTACTAACATCTGTCCGC-3′; human snail-forward, 5′-CCTCAAGATGCACATCCGAAG-3′; human snail-reverse, 5′-ACATGGCCTTGTAGCAGCCA-3′; human fibronectin-forward, 5′-GTGTTGGGAATGGTCGTGGGGAATG-3′; human fibronectin-reverse, 5′-CCAATGCCACGGCCATAGCAGTAGC-3′; human 18S rRNA-forward, 5′-CTCAACACGGGAAACCTCAC-3′; and human 18S rRNA-reverse, 5′-AGACAAATCGCTCCACCAAC-3′.…”

FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-β–mediated EMT in cervical cancer cells

“…Total RNA was extracted with RNAiso Plus (TaKaRa) according to the manufacturer’s instructions. Reverse transcription and qPCR were performed as described 47 . The specific primers for human snail , slug , and fibronectin were as follows: human snail -forward, 5′-cctcaagatgcacatccgaag-3′; human snail -reverse, 5′-acatggccttgtagcagcca-3′; human slug -forward, 5′-cccacacattaccttgtgtttgcaa-3′; human slug -reverse, 5′-caaatgctctgttgcagtgagg-3′; human fibronectin -forward, 5′-gtgttgggaatggtcgtggggaatg-3′; human fibronectin -reverse, 5′-ccaatgccacggccatagcagtagc-3′.…”

“…Cells were lysed in radioimmunoprecipitation assay buffer as previously described 47 . Equal amounts of total protein were resolved using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were transferred to a polyvinylidene difluoride membrane, and probed using primary antibodies and secondary antibodies conjugated with horseradish peroxidase (Jackson ImmunoResearch Laboratories).…”