Chronic Sleep Fragmentation During the Sleep Period Induces Hypothalamic Endoplasmic Reticulum Stress and PTP1b-Mediated Leptin Resistance in Male Mice

• DOI: 10.5665/sleep.4320
• Publication Date: 2014-12-31T15:38:37Z
• Authors: Fahed Hakim; Yang Wang; Alba Carreras; Camila Hirotsu; Jing Zhang; Eduard Peris; David Gozal
• Keywords: Tauroursodeoxycholic acid; Leptin receptor

Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain the metabolic syndrome. Increased endoplasmic reticulum (ER) stress activation of unfolded protein response (UPR) leading attenuation leptin receptor signaling in hypothalamus leads obesity dysfunction.Mice were exposed SF sleep control (SC) for varying periods time during which ingestive behaviors monitored. UPR pathways assessed hypothalami. To further examine mechanistic role ER stress, changes (ObR) also examined wild-type mice treated with chaperone tauroursodeoxycholic acid (TUDCA), as well CHOP-/+ transgenic mice.Fragmented male induced increased food intake starting day 3 thereafter, was preceded by increases all three hypothalamus. Although ObR expression unchanged, signal transducer activator transcription (STAT3) phosphorylation decreased, suggesting reduced signaling. Unchanged suppressor cytokine signaling-3 (SOCS3) protein-tyrosine phosphatase 1B (PTP1B) activity emerged SF, along p-STAT3 responses exogenous leptin. SF-induced effects reversed following TUDCA treatment absent CHOP -/+ mice.SF induces hyperphagic that are mediated ultimately lead PTP1B activity. therefore potentially implicated dysfunction, represent a viable therapeutic target.