Published March 26, 2020 - More info
Research shows that rats and humans on a high-fat diet (HFD) are less sensitive to satiety signals known to act via vagal afferent pathways. We hypothesize that HFD causes an upregulation of 2-pore domain potassium channels, resulting in hyperpolarization of nodose ganglia (NG) and decreased vagal response to satiety signals, which contribute to hyperphagia. We show that a 2-week HFD caused an upregulation of 2-pore domain TWIK-related spinal cord K+ (TRESK) and TWIK-related acid-sensitive K+ 1 (TASK1) channels by 330% ± 50% and 60% ± 20%, respectively, in NG. Patch-clamp studies of isolated NG neurons demonstrated a decrease in excitability. In vivo single-unit NG recordings showed that a 2-week HFD led to a 55% reduction in firing frequency in response to CCK-8 or leptin stimulation. NG electroporation with TRESK siRNA restored NG responsiveness to CCK-8 and leptin. Rats fed a 2-week HFD consumed ~40% more calories compared with controls. Silencing NG TRESK but not TASK1 channel expression in HFD-fed rats restored normal calorie consumption. In conclusion, HFD caused upregulation of TRESK channels, resulting in NG hyperpolarization and decreased vagal responsiveness to satiety signals. This finding provides a pharmacological target to prevent or treat HFD-induced hyperphagia.
Gintautas Grabauskas, Xiaoyin Wu, ShiYi Zhou, JiYao Li, Jun Gao, Chung Owyang
Original citation: JCI Insight. 2019;4(17):e130402. https://doi.org/10.1172/jci.insight.130402
Citation for this corrigendum: JCI Insight. 2020;5(6):e137859. https://doi.org/10.1172/jci.insight.137859
In addition, the Methods section incorrectly indicated the manufacturer and catalog number for the TRESK antibody used for immunocytochemistry. The corrected statement appears below.
Immunocytochemistry studies to localize TRESK (sc-51240, Santa Cruz Biotechnology) and CCK-AR (sc-270029, Cell Signaling Technology) were performed on vagal sensory ganglia as described previously (12).
The online version of the article has been updated with the corrected information.
The authors regret the errors.