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BK channel β1‐subunit deficiency protects against high fat diet‐induced metabolic disorders in the absence of hypertension and exacerbated vascular fibrosis/remodeling in female mice
Author(s) -
Xu Hui,
Fernandes Roxanne,
Garver Hannah,
Galligan James J,
Fink Gregory D
Publication year - 2017
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.31.1_supplement.691.2
Subject(s) - endocrinology , medicine , hyperinsulinemia , fibrosis , blood pressure , bk channel , adipose tissue , insulin resistance , diabetes mellitus , potassium channel
Metabolic disorders reduce the expression and/or increase the degradation of BK channel β1‐subunits and cause vascular BK channel deficiency, which is associated with metabolic vascular dysfunction/remodeling in male mice. The contributions of vascular BK channel s to control of blood pressure and vascular function/structure have not been studied in female mice. Since estrogen is a potent BK channel activator that protects against metabolic disorder associated cardiovascular dysfunction in premenopausal women , we anticipated that the metabolic disorder associated vascular dysfunction/remodeling would be exacerbated in female BK channel β1‐subunit knockout (KO) mice. 32 weeks of high fat (HF) feeding of female wild‐type (WT) mice caused obesity , moderate hyperglycemia and hyperinsulinemia, hyperlipidemia, hyperleptinemia, and moderate hyperaldosteronism. Compared with HF‐WT mice, female HF‐BK b1‐KO mice showed delayed development of obesity and body weight gain, less visceral adipose accumulation, lower plasma leptin and cholesterol levels, and more adrenal gland hypertrophy. Contractile responses to norepinephrine were unchanged in pressurized MA in vitro in HF‐WT mice, but the responses were significantly reduced in MA from HF‐BK β1‐KO mice , compared with control diet fed mice. All female BK β1‐KO mice were normotensive but exhibited moderate hyperaldosteronism when blood pressure was measured by telemetry. HF‐WT and all BK β1‐KO mice displayed blunted BK channel function in pressurized MA in vitro. All HF mice did not show significant functional and morphological changes to support the exacerbated arterial remodeling/fibrosis and inflammatory responses in mesentery, heart and kidney. Our studies showed that HF diet promotes vascular BK channel deficiency but does not promote hypertension and vascular remodeling/fibrosis in female mice. The non‐vascular BK b1‐subunit deficiency may involve in protection against high fat diet induced metabolic disorders. Support or Funding Information Supported by NIH2P01HL070687‐11A1