Modulation of mitochondrial nitric oxide synthase in cold adaptation

FINOCCHIETTO P; PERALTA J; CONVERSO D; CARRERAS MC; SCHÖPFER F; PODEROSO JJ

Mar del Plata

Congreso; II Congress South American Group for Free Radical Research.; 2001

South American Group for Free Radical Research.

The recently discovered mitochondrial nitric oxide synthase (mtNOS) is able to regulate oxygen uptake in organelles isolated from different tissues. This effect includes a reversible binding to cytochrome oxidase in competition with oxygen. The present study was devoted to study the time- course of variations in systemic and liver mitochondrial O2   uptake as related to changes in liver (mtNOS) expression and  activity during 24 days rat cold adaptation. To that purpose, we studied 50 Sprague-Dawley rats exposed to 4ºC (cold) and 23ºC (controls) (250 g weight) and measured systemic O2 uptake in an open-circuit system, mitochondrial O2uptake by polarography, mtNOS by Western blot with an anti-iNOS antibody and activity by 3H-citrulline production. The results showed that cold elicited a biphasic response in systemic O2 uptake characterized by an increasing slope up to +38% at  7-10th days (period A) and thereafter by a decrease to baseline values at the end of the experience (period B). Rats in the cold group lost 12% weight in period A which was further recovered in period B. Changes in body weight reflected fat mobilization and deposition as judged by variations in plasma free fatty acids and noradrenaline. In addition, food intake increased early and was almost duplicated along the study (54±4 vs 114±11g/kg weight/day in controls and cold groups, respectively). Liver mtNOS  expression and activity increased from 6th day and was sustained up to the end of the experience; activity rose from 50 to 85-90 pmoles NO/min.mg mitochondrial protein, p<0.05). In period B, mitochondrial O2 uptake was selectively modulated by L-arginine availability or by the utilization of NOS inhibitor L-NMMA leading, in the same days, to 8-50% decrease in mitochondrial O2 uptake. It is suggested that late variations in systemic and mitochondrial O2  uptake during cold acclimation may result from activation of mtNOS and NO release (low O2 uptake and fat deposition, period B); otherwise, early changes are likely associated to shivering, lipolysis and release of catecholamines (pro-calorigenic effects, period A).  Therefore, changes in weight gain during cold exposure could reflect in part an influence of mtNOS on the balance between energy intake and expenditure.