Premium
Metabolic Dysfunction in Chronic Intermittent Hypoxia‐ Role of Hypothalamic Peptides
Author(s) -
Nedungadi T.Prashant,
Mifflin Steve W,
Cunningham J.Thomas
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.906.19
Subject(s) - endocrinology , medicine , hypothalamus , corticosterone , neuropeptide y receptor , intermittent hypoxia , obstructive sleep apnea , neuropeptide , chemistry , receptor , hormone
Obstructive sleep apnea (OSA) is associated with an increase in cardiovascular risk factors that includes metabolic syndrome and hypertension. Our model of Chronic Intermittent Hypoxia (CIH) mimics the hypoxemia and the persistently elevated arterial pressure seen in OSA patients. We examined if metabolic dysfunction associated with CIH is initiated through changes in neuropeptides in the arcuate nucleus (ARH) and paraventricular nucleus (PVN) of the hypothalamus. Adult male rats were exposed to 7 d of CIH or 7 d of normoxia (CON). Increases in body weight were higher in CON compared to CIH (CON: 25 ± 2.5; CIH: 16 ± 2.7). Urinary corticosterone (CORT) was elevated 6 fold in CIH exposed rats. Laser capture microdissection of ARH and PVN followed by RT‐PCR showed significant increase in ÄFosB mRNA in both PVN and ARH (PVN CON: 1± 0.1 vs PVN CIH: 1.96 ± 0.14; ARH CON: 1 ± 0.18 vs ARH CIH: 2.5 ± 0.5), and immunohistochemical observations suggest that CIH elevated FosB in both these regions. Neuropeptide Y (NPY) mRNA levels were elevated after CIH in ARH (CIH: 1.7 ± 0.5 vs CON: 0.3 ± 0.1). In PVN, Insulin receptor (InsR) mRNA was decreased while CORT releasing factor (CRF) mRNA was significantly elevated after CIH (InsR CIH: 1.1 ± 0.3 vs InsR CON: 2.9 ± 0.5; CRF CON: 1.8 ± 0.8 vs CRF CIH: 5.5 ± 1.1). Hence, metabolic dysfunction associated with CIH might be initiated centrally through peptides in the ARH‐PVN hypothalamic circuitry. P01 HL88052