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Apelin Icv Infusion Blunts Brain ACE 2 Overexpression‐mediated Metabolic Abnormalities in Mice
Author(s) -
Xia Huijing
Publication year - 2015
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.29.1_supplement.655.8
Subject(s) - apelin , medicine , endocrinology , hypothalamus , homeostasis , in vivo , chemistry , energy homeostasis , metabolism , carbohydrate metabolism , obesity , biology , receptor , microbiology and biotechnology
We previously reported that transgenic mice overexpressing ACE2 in the brain (SA) exhibit age‐dependent impaired metabolic function. Apelin is involved in the central regulation of energy and glucose homeostasis. ACE2 cleaves Apelin‐13 and 36 in vitro, however, the effect in vivo is unknown. We hypothesized that ACE2 overexpression alters apelin signaling in the brain, leading to metabolic dysfunction. To test this, hypothalamus Apelin levels, daily food intake, body weight, fasting blood glucose (16 h fasting) and glucose tolerance (measure blood glucose at 0, 15, 30, 60, 120 min after IP injection of glucose 2 g/kg) were determined in SA and wildtype mice (24wks old, n=5). In another set of experiments, SA mice were infused with Apelin‐13 (icv, 40 ng/d, osmotic pump) for 4 wks, metabolic parameters were measured before and after infusion. Interestingly, a significant reduction in hypothalamus Apelin level was observed in SA mice compared to wildtype (1.2±0.16 vs. 2.0±0.14 fmol/mg). This was concomitant with increased food intake (0.12±0.01 vs. 0.09±0.01 g/g), higher body weight (39±1.5 vs. 31±0.8 g), elevated fasting blood glucose (147.8±13 vs.106.5±7 mg/dl) and impaired glucose tolerance (AUC: 51.6±2 vs. 41.5±1.7) in these animals (P<0.05). Following Apelin‐13 infusion, although food intake in SA mice was not affected (P>0.05), body weight was significantly reduced compared to pre‐infusion (38±1.1 vs. 44±1.1 g, P<0.05). In addition, Apelin‐13 infusion significantly decreased fasting blood glucose level (113±7 vs. 168±22 mg/dl) and improved glucose tolerance (AUC: 43±8 vs. 72±4) in SA mice (P<0.05 vs. Pre‐infusion). These data suggest that central ACE2‐overexpression decreases Apelin levels in the brain, thus contributing to metabolic abnormalities. (NIH P20 GM103514)