Norepinephrine dependent inhibition of proteolysis in brown adipocytes

Brown adipose tissue (BAT) is specialized for heat production. Brown adipocytes contain an uncoupling protein (UCP-1) in the mitochondria, which uncouples oxidative phosphorylation and produces heat. Thermogenesis in BAT is under the control of sympathetic nervous system. In addition, BAT growth and atrophy occurs in response to changes in the sympathetic activity. So, the focus of this research was to evaluate the mechanism by which norepinephrine (NE) affects proteolysis in brown fat cells differentiated in culture. An inhibitory effect of NE on proteolysis and ATP level was observed in mature brown adipocytes but not in pre-adipocytes and 3T3-L1 adipocytes. The inhibitory effect of NE was not affected by the amount of UCP1 in mature brown adipocytes. To see if NE's action on proteolysis in mature brown adipocytes was linked to the onset of thermogenesis via activation of UCP-1 and decreasing energy level of the cell, the effect of NE on proteolysis and ATP was compared with that of fatty acids known to activate UCP-1 directly. Unlike in pre-adipocytes and 3T3-L1 adipocytes, both proteolysis and cell ATP level were decreased in mature brown adipocytes. Furthermore, bromopalmitate, a non-metabolisable fatty acid, which is known to activate UCP-1, reduced proteolysis and ATP by a greater extent than NE. There was a linear relationship between reduction in cell ATP and protein degradation. So, NE may inhibit proteolysis in mature brown adipocytes by decreasing the cell ATP level, and thus may play a significant role in affecting the cell content of protein under certain physiological and pathological conditions, known to activate thermogenesis and stimulate BAT growth