2001-P: Thermoneutrality Dissociates Glucose Tolerance from Insulin Sensitivity in Rats

Thermoneutrality (TN) has been used to induce weight gain in rodent models of obesity. We hypothesized that TN would potentiate high-fat diet (HFD) impairment of vascular reactivity, diminish vascular mitochondrial function, and induce insulin resistance. Male rats aged 5-7 weeks were housed at room temperature (RT=23 C) or TN (29 C) and fed a low-fat diet (LFD) or HFD for 10-16 weeks. Aortic vasomotion and mitochondrial respiration (Oroboros O2k) were measured at the end of the study. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were done at baseline and endpoint. Animals housed at TN had impaired vasodilation regardless of diet (effect of temperature, p<0.01). We also observed an elevated constriction response to phenylephrine in TN animals (interaction of temperature x concentration, p=0.023). Animals on HFD housed in both environments had diminished mechanical constriction (effect of diet, p=0.007). Animals housed at TN had elevated rates of both ADP-independent and dependent respiration (effect of temperature, p<0.001 for both). Metabolic profiling revealed that TN lowered glucose tolerance (interaction of temperature x time p<0.001). Fasting glucose was lower at endpoint in TN rats (interaction of time x temperature, p=0.004). Unexpectedly, glucose uptake improved in TN during an IP-ITT but worsened with RT (effect of temperature, p=0.023). IP-ITT insulin clearance in TN animals at endpoint was impaired (interaction of time x diet p=0.002). There was a significant effect of temperature on fat pad weight (p=0.034) with no effect on overall weight. In sum, TN provides a robust tool for inducing vascular dysfunction. A TN climate led to significant alterations in metabolism. Further experiments are underway to clarify potential mechanisms for the unexpected TN-mediated increased insulin sensitivity with concomitant glucose intolerance. Disclosure A.C. Keller: None. L. Knaub: None. S.E. Hull: None. R.L. Scalzo: None. L.A. Walker: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. Funding U.S. Department of Veterans Affairs (BX003185-01A2, BX002046, CX001532); National Institutes of Health (5T32HL007171)