Low intrinsic aerobic fitness increases susceptibility to OVX‐induced obesity and insulin resistance in the absence of adipose tissue inflammation (1028.3)

While female rodents are protected from obesity‐associated adipose tissue (AT) inflammation compared to males, ovariectomy (OVX) (in mice) results in AT inflammation and insulin resistance (IR). The extent to which intrinsic aerobic fitness protects against inflammation and metabolic dysfunction associated with ovarian hormone loss is not known. Here, 43 normal chow diet (NC)‐fed rats selectively bred for high (HCR) and low (LCR) intrinsic aerobic fitness were followed from 16‐36 wks of age and compared for their response to OVX, performed at 25 wks of age; 11 wks later, the 4 groups (HCR‐SHM, LCR‐SHM, HCR‐OVX, LCR‐OVX) were compared for weight gain, % fat (DXA), visceral AT (VAT) mass, immune cell composition and inflammation (FACS and rtPCR for cytokines, Mφ, and T‐cell markers), and HOMA (IR). LCR‐OVX rapidly gained weight, were 73% fatter, had ~2X more VAT, and had 90% higher IR than LCR‐SHM (all grp X line interaction, p<0.01). There was no effect of OVX on any of these parameters in HCR. Despite increased adiposity and IR in LCR‐OVX, AT inflammation was not detected, suggesting that low aerobic fitness results in OVX‐associated weight gain and IR in the absence of AT inflammation within the first 8 wks following OVX on NC. Ongoing studies will determine the influence of intrinsic aerobic fitness on metabolic function in response to OVX under high fat diet conditions. Grant Funding Source : Supported by University of Missouri Research Council Grant (to VVP), NIH R01DK088940 (to JT), ROD01