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

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 degrees or 6 degrees C for 2 hr and then received a bolus infusion of [14C]-2DG (125 microCi/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 degrees +/- 0.3 degrees; female, 36.1 degrees +/- 0.2 degrees 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Cold-Induced Thermoregulation and Biological Aging

“…The results from investigations evaluating the influcle, estimated from in vivo cellular incorporation of 2ence of age-related muscle atrophy on cold-exposure in [ 14 C]deoxyglucose, does not increase significantly during aging rodents suggest that exercise training increases heat cold exposure in younger or older, male or female, F344 production (112,154,155). Oxygen consumption during rats (113). Moreover, serum insulin levels decline significold exposure of aging male F344 rats trained for 6 mo cantly during cold exposure (51, 156,161).…”

“…In addition, the observation in humans that dences of hypothermia (23). Although some clinical and older females tend to maintain core temperature in the epidemiological evidence may support the suggestion that cold better than do males is supported by the animal work CIT declines with aging, the influence of biological aging (51, 107,109,113). on the ability to maintain normal body temperature during cold exposure is difficult to precisely determine from these types of investigations.…”

Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans

“…Caucasians living in Western Europe may have required efficient thermogenesis to cope with cold climates. Lipids from fat, but not glucose, contribute to thermogenesis during exposure to cold [18]. However, a recent study that investigated the Y chromosome and mitochondrial DNA (both parts of the DNA which do not show recombination) in 2000 Dutch men showed that 80% originated from hunter-gatherers that already populated Western Europe 25,000 year ago (http://www.nrcnext.nl/nieuws/wetenschap/article2030713.ece, article in Dutch).…”

Perspectives on Brown Adipose Tissue Imaging: Insights from Preclinical and Clinical Observations from the Last and Current Century

“…Presence of active BAT on 18 F-FDG PET/CT images has also been linked, in some studies, to lower fasting glucose levels and colder outdoor temperatures (12,27). Data from rodent studies support a decrease in BAT mass and function with increasing age (28). In humans, Yoneshiro et al described a BAT prevalence rate of 53% in subjects 20-30 y of age and 7% in subjects 50 y of age or older (29).…”