Age and Gender Effects on Glucose Utilization in Skeletal Muscle and Brown Adipose Tissue of Cold-Exposed Rats

Abstract

Abstract

We hypothesized that glucose utilization by skeletal muscle is less in cold-exposed older male versus female Fischer 344 (F344) rats and that this reduction may contribute to the poorer cold-exposed thermoregulatory ability of the older males. To test this hypothesis, the rates of in vivo glucose utilization of skeletal muscle in 6-, 12-, and 26-month-old male and female F344 rats were estimated during cold exposure by measuring the cellular incorporation of [¹⁴C]-2-deoxyglucose ([¹⁴C]-2DG) after its conversion to [¹⁴C]-2DG-6-phosphate ([¹⁴C]-2DGP). Comparable measurements were also made in the interscapular brown fat depot (IBAT). Four-hour fasted rats, that had been fitted with femoral arterial and venous cannulae 24 hr earlier, were exposed to either 26° or 6°C for 2 hr and then received a bolus infusion of [¹⁴C]-2DG (125 μCi/kg body wt). Arterial plasma glucose and [¹⁴C]-2DG concentrations were measured periodically for an additional 45 min. Rats were sacrificed, and various skeletal muscles and IBAT were removed and immediately frozen in liquid N₂ for subsequent analysis of [¹⁴C]-2DGP content. Cold-exposed male rats had significantly lower rectal temperatures than comparably treated females (26-month-old male, 34.8° ± 0.3°; female, 36.1° ± 0.2°C). There was no main effect of age, gender, or cold exposure on skeletal muscle glucose utilization when the data were expressed as nmol/min/g. In contrast, when data were expressed relative to total tissue weight (nmol/min), skeletal muscle glucose utilization was significantly higher in male than in female rats. Although estimated glucose utilization in IBAT (nmol/min/g) isolated from cold-exposed rats was significantly greater than that in brown fat isolated from non-cold-exposed animals, there was no main effect of age or gender. However, glucose utilization per IBAT depot (nmol/min) was significantly less in older male than in female rats, and reflected the fact that IBAT weight of older males was more than 50% lower than that of comparably aged females. Thus, our hypothesis that reduced skeletal muscle glucose utilization contributes to the blunted thermoregulatory ability of older male versus female F344 rats is negated. Rather, our data suggest that while the ability of brown adipocytes to utilize glucose does not appear to decline with age (as indicated by the absence of an age-related decrease in glucose utilization per gram of IBAT), the lower total depot glucose utilization of cold-exposed older males versus females may partially explain the previously reported gender difference in the thermogenic capacity of this tissue.