Retraction Open Access | 10.1172/jci.insight.169516
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Published February 22, 2023 - 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 retraction: JCI Insight. 2023;8(4):e169516. https://doi.org/10.1172/jci.insight.169516
The University of Michigan recently notified JCI Insight of concerns regarding the identity of the antibodies used in Figure 2. JCI Insight previously issued a corrigendum to update the source of the TRESK and CCK-AR antibodies used for immunocytochemistry; however, the antibodies listed in the corrigendum were not correct (1). The institutional investigation determined that there was falsification of immunocytochemistry data by the improper description of the species of antibody used in Figure 2 and that falsified data were intentionally, knowingly, or recklessly included in the publication. Due to the intentional inclusion of falsified data and continued concerns over the identity of antibodies, JCI Insight is retracting this article.
See the related article at High-fat diet induced vagal afferent dysfunction via upregulation of two-pore potassium TRESK channel.