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Effects of Ovarian Hormone Loss and Aerobic Fitness on Brown Adipose Tissue Immunometabolic Characteristics in Rats
Author(s) -
VieiraPotter Victoria Jeanne,
Park YoungMin,
Zidon Terese M.,
Welly Rebecca J.
Publication year - 2016
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.30.1_supplement.1288.19
Subject(s) - endocrinology , medicine , brown adipose tissue , adipose tissue , insulin resistance , white adipose tissue , analysis of variance , ovary , adipokine , biology , insulin , inflammation
Ovary‐intact female rodents are less susceptible to white adipose tissue (WAT) inflammation and insulin resistance (IR). Females also are known to have greater brown adipose tissue (BAT) activity and uncoupling protein (UCP)‐1 expression. Ovary removal (i.e., OVX) increases adiposity, WAT inflammation, and IR. We recently demonstrated that female rats selectively bred for high running capacity (i.e., high‐fit HCR), compared to those bred for low running capacity (i.e., low‐fit LCR), are protected against OVX‐associated weight gain and IR and have more BAT, which correlates strongly with their greater resting energy expenditure. The objectives of the present study were to determine: 1) how HCR and LCR rats differ in their interscapular BAT immunometabolic characteristics; and 2) how OVX affects BAT of HCR and LCR rats. HCR and LCR rats had OVX or SHM (i.e., sham ovariectomy) surgeries at 25 weeks of age and were followed for up to 27 weeks, during which time they remained sedentary and were fed standard rodent chow. Food intake, weight gain, adiposity ( DXA and fat pad weights ), circulating adipokines ( ELISA ), spontaneous cage physical activity (SPA) ( metabolic cages with beam break quantification ) and insulin sensitivity ( hyperinsulinemic euglycemic clamps ) were compared among the 4 groups via 2‐way ANOVA to determine main effects of line (i.e., HCR v. LCR), treatment (i.e., OVX v. SHM), and line × treatment interactions (which were followed by LSD multiple comparison tests, as appropriate); correlations are Pearson bivariate. Statistical analyses were performed using SPSS v21 and P<0.05 was considered significant. BAT was assessed via UCP‐1 immunostaining, gene ( rtPCR ) and protein ( Western ) expression, citrate synthase activity ( enzyme assay ), and insulin‐mediated glucose uptake under clamp conditions. While HCR and LCR rats did not differ in histological, gene, enzymatic, or protein indexes of non‐stimulated BAT activity, HCR had lower BAT inflammatory cytokine (e.g., TNF‐a) and T cell (e.g., CD3, CD4) gene expression (all P<0.05 compared to LCR) and markedly greater insulin‐stimulated glucose uptake into BAT (P<0.01 compared to LCR), which was strongly related to their improved systemic glucose infusion rate (r = 0.5, P=0.014). In both HCR and LCR rats, OVX reduced skeletal muscle insulin sensitivity (P<0.02) but did not affect insulin‐stimulated glucose uptake into WAT or BAT. Unexpectedly, in HCR and LCR rats, OVX increased BAT UCP‐1 and reduced several inflammatory genes (e.g., TNF‐a, CD3, CD4, CD8, all P<0.05). We hypothesize that UCP‐1 up‐regulation following OVX may be a compensatory defense mechanism against oxidative stress resulting from OVX. Support or Funding Information MU Research Council Grant to VJ Vieira‐Potter