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The Journal of Physiology - 2022 - Kim - TRPM7 channels regulate breathing during sleep in obesity by acting peripherally (4).pdf (3.61 MB)
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TRPM7 channels regulate breathing during sleep in obesity by acting peripherally

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journal contribution
posted on 2023-01-27, 16:46 authored by Lenise KimLenise Kim, Mi-Kyung Shin, Huy Pho, Wan-Yee Tang, Nishitha Hosamane, Frederick Anokye-Danso, Rexford S. Ahima, James SK Sham, Luu V. Pham, Vsevolod Y. Polotsky

Sleep-disordered breathing (SDB) affects over 50% of obese individuals. Exaggerated hypoxic chemoreflex is a cardinal trait of SDB in obesity. We have shown that leptin acts in the carotid bodies (CB) to augment chemoreflex and that leptin activates the transient receptor potential

melastatin 7 (TRPM7) channel. However, the effect of leptin-TRPM7 signalling in CB on breathing and SDB has not been characterized in diet-induced obesity (DIO). We hypothesized that leptin acts via TRPM7 in the CB to increase chemoreflex leading to SDB in obesity. DIO mice were implanted with EEG/EMG electrodes and transfected with Leprb short hairpin RNA (shRNA) or Trpm7 shRNA vs. control shRNAin the CB area bilaterally. Mice underwent a full-polysomnography and metabolic studies at baseline and after transfection. Ventilatory responses to hypoxia and hypercapnia were assessed during wakefulness. Leprb and Trpm7 were upregulated and their promoters were demethylated in the CB of DIO mice. Leprb knockdown in the CB did not significantly affect

ventilation. Trpm7 knockdown in the CB stimulated breathing during sleep in normoxia. These effects were not driven by changes in CB chemosensitivity or metabolism. Under sustained hypoxia, Trpm7 shRNA in the CB augmented ventilation during sleep, but decreased oxyhaemoglobin saturation. We conclude that the suppression of TRPM7 in the CB improved sleep-related hypoventilation and that the respiratory effects of CB TRPM7 channels in obesity are independent of leptin. TRPM7 signalling in the CB could be a therapeutic target for the treatment of obesity-related



Grant ID

AHA Postdoctoral Fellowship Award 828142

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