Redox state of brown adipose tissue as a possible determinant of its blood flow

Abstract

During norepinephrine (NE) induced thermogenesis in the adipocytes of brown adipose tissue (BAT), the blood flow of the tissue, and thus its oxygen supply, seems to be controlled by the adipocytes, possibly through their production of a vasodilator. This study sought to discover a metabolic parameter of the adipocytes that might account for modulation of vasodilator production and BAT blood flow. The blood flow of the interscapular BAT (IBAT) of anesthetized, cold-acclimated rats was varied by infusing NE and by altering the concentration of oxygen in arterial blood (AO2). Flow was measured with radiolabeled microspheres. IBAT was freeze fixed in situ for determination of its levels of adenine nucleotides and its cytosolic redox state; the latter was measured in terms of the concentration ratios, lactate/pyruvate (L/P) and glycerol-3-phosphate/dihydroxyacetone phosphate (GP/DHAP) in the tissue. The increase in IBAT blood flow with dose of NE was associated with a progressive decline in tissue ATP, increases in ADP and AMP at high doses of NE, and progressive increases in L/P and GP/DHAP, the latter increases indicating increased reduction of the cytosolic NAD+-NADH system. Reducing AO2 by hemodilution raised the blood flow, L/P, and GP/DHAP of IBAT to values significantly above those measured in rats of normal AO2 given the same doses of NE; whereas, elevating AO2 by hemoconcentration had the opposite effects on these values. For rats of normal or altered AO2 together, a correlation coefficient of 0.94 was obtained for the relation between IBAT blood flow and L/P and one of 0.85 for that between flow and GP/DHAP.(ABSTRACT TRUNCATED AT 250 WORDS)