Effects of ovariectomy and intrinsic aerobic capacity on tissue-specific insulin sensitivity

Abstract

High-capacity running (HCR) rats are protected against the early (i.e., ∼ 11 wk postsurgery) development of ovariectomy (OVX)-induced insulin resistance (IR) compared with low-capacity running (LCR) rats. The purpose of this study was to utilize the hyperinsulinemic euglycemic clamp to determine whether 1) HCR rats remain protected from OVX-induced IR when the time following OVX is extended to 27 wk and 2) tissue-specific glucose uptake differences are responsible for the protection in HCR rats under sedentary conditions. Female HCR and LCR rats (n = 40; aged ∼ 22 wk) randomly received either OVX or sham (SHM) surgeries and then underwent the clamp 27 wk following surgeries. [3-(3)H]glucose was used to determine glucose clearance, whereas 2-[(14)C]deoxyglucose (2-DG) was used to assess glucose uptake in skeletal muscle, brown adipose tissue (BAT), subcutaneous white adipose tissue (WAT), and visceral WAT. OVX decreased the glucose infusion rate and glucose clearance in both lines, but HCR had better insulin sensitivity than LCR (P < 0.05). In both lines, OVX significantly reduced glucose uptake in soleus and gastrocnemius muscles; however, HCR showed ∼ 40% greater gastrocnemius glucose uptake compared with LCR (P < 0.05). HCR also exhibited greater glucose uptake in BAT and visceral WAT compared with LCR (P < 0.05), yet these tissues were not affected by OVX in either line. In conclusion, OVX impairs insulin sensitivity in both HCR and LCR rats, likely driven by impairments in insulin-mediated skeletal muscle glucose uptake. HCR rats have greater skeletal muscle, BAT, and WAT insulin-mediated glucose uptake, which may aid in protection against OVX-associated insulin resistance.

Voluntary Running Attenuates Metabolic Dysfunction in Ovariectomized Low-Fit Rats

“…We recently demonstrated that LCR rats are more susceptible to ovariectomy-associated metabolic dysfunction (25, 40) and the combination of ovariectomy plus HFD (24) compared to HCR. EX is a highly effective treatment to reverse metabolic dysfunction including insulin resistance via enhancing aerobic capacity (6, 17).…”

“…Ovariectomy surgeries were conducted as previously described (25). All rats were anesthetized by inhaled isofluorane at 2% during surgery.…”

“…A recent study demonstrated that female LCR rats have impaired skeletal muscle mitochondrial function assessed by cytochrome c protein and fatty acid oxidation (20), which is associated with insulin resistance and greater susceptibility to metabolic syndrome (31). Our group has demonstrated that LCR rats are susceptible to ovariectomy-induced insulin resistance and the accumulation of adiposity, while HCR rats are impervious to ovariectomy with respect to those variables (25, 40). Furthermore, we recently demonstrated that, following ovariectomy, LCR rats are more susceptible to high fat diet (HFD)-induced adiposity and insulin resistance than HCR rats (24).…”

Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression

“…We also recently demonstrated a strong impact of ovarian hormones on metabolic function (i.e., tissue-specific insulin sensitivity) independent of intrinsic aerobic capacity level [41]. Among ovarian hormones, circulating E 2 is the critical mediator of physical activity in female animals.…”

Intrinsic (Genetic) Aerobic Fitness Impacts Susceptibility for Metabolic Disease

“…Recent studies continue to match findings in this model to those in humans. LCR rats have now been shown to be more susceptible to a variety of other conditions that are also linked to low aerobic capacity in humans (16, 26, 39). …”