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Obesity related hypertension: an altered downstream regulation of leptin signaling (682.5)
Author(s) -
Lim Kyungjoon
Publication year - 2014
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.28.1_supplement.682.5
Subject(s) - medicine , endocrinology , leptin , neuropeptide y receptor , hypothalamus , blood pressure , hormone , chemistry , obesity , neuropeptide , receptor
Background: Short term (3weeks) high fat diet (HFD) consumption leads to an increase in blood pressure (BP) and renal sympathetic nerve activity (RSNA) in rabbits. We suggest there is an altered down‐stream sensitivity of leptin in the hypothalamus which involves altered responses to α‐melanocyte stimulating hormone (α‐MSH) and neuropeptide Y (NPY) when rabbits are fed a HFD. Aim: To investigate the role of α‐MSH and NPY in the hypothalamus in HFD‐fed rabbits. Methods: New Zealand White Rabbits were fed with a normal or a 13.3% HFD for 3 weeks. A bilateral guide cannula into the dorsomedial (DMH) or ventromedial hypothalamus (VMH) and an RSNA recording electrode was implanted. After 3 weeks on the diet, α‐MSH (0.1, 0.3nmol), NPY (0.1, 0.5nmol) or Ringer’s were injected directly into the DMH or VMH. Results: Rabbits exhibited higher BP, HR and RSNA when fed a HFD compared to controls (n=6‐8). α‐MSH injection into the DMH increased BP (5.7%, P<0.05 and 8.3%, P<0.01 with 0.1nmol and 0.3nmol respectively) and RSNA (40%, P<0.05 with 0.3nmol) in HFD rabbits. When α‐MSH was injected into the VMH, BP was unchanged but RSNA was increased (28%, P=0.01 and 38%, P<0.01) in HFD rabbits. NPY injection had no effect in both control and HFD rabbits. Conclusion: Elevated blood pressure and sympatho‐excitation in HFD rabbits are due to increased sensitivity of the leptin signalling pathway which involves a dorsal and ventral hypothalamic projection of α‐MSH activated second order neurons.