The Roles of Different Adipose Depots in Glutamine Metabolism following Feeding, Fasting and Exercise in the Guinea-Pig

Digby, Janet Elizabeth (1998). The Roles of Different Adipose Depots in Glutamine Metabolism following Feeding, Fasting and Exercise in the Guinea-Pig. PhD thesis The Open University.



This study investigates the activities of glutaminase and glutamine synthetase the two principle enzymes of glutamine metabolism, over a time course, in adipose tissue from eleven different sites of adult male guinea-pigs after feeding, fasting and exercise. In addition, the uptake and release of glutamine was measured in isolated adipocytes from five of these adipose sites in the presence of insulin, or the synthetic hormone analogues dexamethasone and isoprenaline.

In the fasted condition, glutaminase and glutamine synthetase activities were greatest in adipose tissue from the subcutaneous inguinal depot and the intra-abdominal omental depot. In the early post-prandial period, glutaminase activity was increased in adipose tissue from all sites measured, the greatest increases being observed in the omental and cervical samples. Glutamine synthetase activity was also increased in the early post-prandial period in the intra-abdominal epididymal depot and in the superficial and intermuscular depots. After exercise, glutaminase activity was decreased in adipose tissue from the inguinal, omental, perirenal, epididymal and popliteal sites. A significant effect of brief, acute exercise was observed in the intraabdominal sites where glutamine synthetase activity was reduced compared to levels in homologous samples from the sedentary fasted guinea-pigs.

Measurements of glutamine uptake and release in isolated adipocytes prepared from different adipose depots incubated with insulin, dexamethasone and isoprenaline showed some site-specific differences that were consistent with the alterations in glutaminase and glutamine synthetase activities in homologous samples after feeding, fasting and exercise. A physiological concentration of insulin stimulated glutamine uptake into isolated adipocytes and the greatest dose-response was observed in the those prepared from the inguinal and omental sites. Glutamine uptake into isolated adipocytes from all depots studied was unaffected by dexamethasone. With isoprenaline, glutamine uptake was lower in adipocytes prepared from the inguinal, mesenteric and omental sites compared to control values. Glutamine release from omental adipocytes was greater than that from adipocytes prepared from any of the remaining sites measured. Dexamethasone enhanced glutamine release from adipocytes prepared from inguinal and epididymal adipose tissue.

These data show that adipose tissue from the relatively large superficial sites have the capacity to contribute significantly to circulating glutamine levels in the fasted and fed state and that the omental site may contribute more to the supply of glutamine to local immune tissues. The data also show that in the fed state the total adipose tissue mass of the guinea-pig may contribute to approximately 30% of the whole-body glutamine release compared to that of muscle. This conclusion is in agreement with a previous in vivo study of human subcutaneous adipose tissue by Frayn et al. (1991) who calculated that adipose may contribute up to a third as much as that of skeletal muscle to whole-body glutamine supply.

Concomittant activity of glutaminase and glutamine synthetase activity in the fasted and fed state coupled to the capacity for adipose tissue to take up and release glutamine suggests the existence of a substrate cycle between glutamine and glutamate in adipose tissue. Such a cycle would enable efficient regulation of glutamine supply to maintain circulating levels, and, when in excess, facilitate storage of glutamine carbons by incorporation into triacylglycerols.

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