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Features of metabolic syndrome in male mice with deficiency of estrogen receptor alpha
Author(s) -
Winn Nathan C,
Jurrissen Thomas,
Lin Gabriela S,
Gastecki Michelle L,
Welly Rebecca J,
Lubahn Dennis B,
VieiraPotter Victoria J,
Padilla Jaume
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.883.11
Subject(s) - endocrinology , medicine , metabolic syndrome , adipose tissue , estrogen receptor , estrogen , fatty liver , leptin , impaired glucose tolerance , inflammation , biology , insulin , insulin resistance , diabetes mellitus , obesity , disease , cancer , breast cancer
Attenuation of estrogen action through estrogen receptor α (ERα) has been implicated in the development of metabolic syndrome in male mice; yet, some studies remain inconclusive which may be attributed to controversy regarding a commonly used mouse model that contains a splice variant of ERα. Herein we examined whether common features of the metabolic syndrome are present in male mice with deficiency of ERα (i.e., bred at our facility), including excess adiposity, adipose tissue inflammation, glucose intolerance, fatty liver, hyperlipidemia, and vascular dysfunction. After weening, C57BL/6J wild type (WT; n=6) and mutated/non‐functional ERα (ERα −/− ; n=7) male mice were fed a standard chow diet for 16 months. Despite no significant differences in body weight or energy intake, ERα −/− mice demonstrated increases in fat mass, visceral adiposity, fatty liver, hyperlipidemia, and glucose and insulin intolerance ( P <0.05). In visceral adipose tissue, both histologic and gene expression markers of immune cell infiltration [CD68, CD11c ( P <0.05), and ITGAM ( P =0.05] were elevated in ERα −/− mice along with increased markers of oxidative stress [p47phox and p22phox (P<0.05)]. Furthermore, ERα −/− mice exhibited impaired endothelium‐dependent vasorelaxation in the aorta ( P <0.05), whereas aortic stiffness ( in vivo or ex vivo, P >0.05) was unaffected. Collectively, our findings support that loss of ERα signaling promotes metabolic and vascular dysfunction in males.