Exercise training is an effective alternative to estrogen supplementation for improving glucose homeostasis in ovariectomized rats

Abstract

The irreversible loss of estrogen (specifically 17-β-estradiol; E2) compromises whole-body glucose tolerance in women. Hormone replacement therapy (HRT) is frequently prescribed to treat estrogen deficiency, but has several deleterious side effects. Exercise has been proposed as an HRT substitute, however, their relative abilities to treat glucose intolerance are unknown. Thirty ovariectomized (OVX) and 20 SHAM (control) rats underwent glucose tolerance tests (GTT) 10 weeks post surgery. Area under the curve (AUC) for OVX rats was 60% greater than SHAM controls (P = 0.0005). Rats were then randomly assigned to the following treatment groups: SHAM sedentary (sed) or exercise (ex; 60 min, 5×/weeks), OVX sed, ex, or E2 (28 μg/kg bw/day) for 4 weeks. OVX ex rats experienced a ∼45% improvement in AUC relative to OVX sed rats, whereas OVX E2 underwent a partial reduction (17%; P = 0.08). Maximal insulin-stimulated glucose uptake in soleus and EDL was not impaired in OVX rats, or augmented with exercise or E2. Akt phosphorylation did not differ in soleus, EDL, or liver of any group. However, OVX ex and OVX E2 experienced greater increases in p-Akt Ser473 in VAT and SQ tissues compared with SHAM and OVX sed groups. Mitochondrial markers CS, COXIV, and core1 were increased in soleus posttraining in OVX ex rats. The content of COXIV was reduced by 52% and 61% in SQ of OVX sed and E2 rats, compared to SHAM controls, but fully restored in OVX ex rats. In summary, exercise restores glucose tolerance in OVX rats more effectively than E2. This is not reflected by alterations in muscle maximal insulin response, but increased insulin signaling in adipose depots may underlie whole-body improvements.

Exercise prevents HFD- and OVX-induced type 2 diabetes risk factors by decreasing fat storage and improving fuel utilization

“…; MacDonald et al. ), this study adds valuable information for the omnipresent physiological state that combines a HFD with the loss of ovarian estrogens, which together provide significant physiological challenges. A previous study demonstrates the ability of exercise to decrease the total body weight and visceral fat weight in the context of a HFD with OVX (Zoth et al.…”

“…While MacDonald et al. () demonstrated that OVX alone can increase the GTT AUC after 10 weeks, Saengsirisuwan et al. () did not see an increase in the GTT AUC 12 weeks post‐OVX.…”

“…Exercise can prevent the OVX‐induced hyperglycemia in the context of a standard diet (MacDonald et al. ), and 6 weeks of exercise training in OVX rats fed a HFD tended to decrease serum insulin levels (although this trend was non‐significant) (Zoth et al. ).…”

“…) or OVX alone (MacDonald et al. ). In human studies, the increased whole body insulin sensitivity in women can be explained by greater glucose uptake into the skeletal muscle (Nuutila et al.…”

Estradiol does not directly regulate adipose lipolysis

“…In our study, using explants, there were no differences in FFA or glycerol release, or HSL phosphorylation in either adipose depot regardless of E2 status. The changes we 32 and others. 7,14 have observed in subcutaneous tissue suggest it may be more affected by the chronic absence of E2.…”