Vol. 277, Issue 2, E215-E222, August 1999
Differentiation-dependent inhibition of proteolysis by
norepinephrine in brown adipocytes
M.
Desautels and
S.
Heal
Department of Physiology, College of Medicine, University of
Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5
The objective was to
evaluate whether norepinephrine (NE) and other hormonal factors have
direct effects on protein degradation in brown fat cells. NE inhibited
proteolysis by 35-45% in mouse brown adipocytes differentiated in
culture. Insulin also inhibited protein degradation but significantly
less than NE, whereas glucagon and leptin had no effect. The inhibitory
effect of NE was partially antagonized by propranolol but not by
prazosin, and dose-response curves with BRL-37344 (a
3-agonist), isoproterenol (a
1/2-agonist) and dobutamide (a 1-agonist)
were consistent with the involvement of a
3-adrenergic receptor.
Furthermore, forskolin mimicked the effects of NE, whereas additions of
A-23187 or phorbol esters had no effect, alone or in combination with
NE or forskolin. Thus inhibition of proteolysis by NE likely involves a
3-adrenergic receptor-mediated
increase in cAMP. In contrast, NE, BRL-37344, and dobutamide had no
effect on proteolysis in preadipocytes. Inhibition of proteolysis by NE
was due at least in part to inhibition of autophagy. Thus inhibition of
proteolysis by NE and insulin in mature brown adipocytes is likely an
important process contributing to brown fat growth and atrophy under
many physiological or pathological conditions.
brown fat; insulin; autophagy; 3-adrenergic receptor; lysosomes; protein turnover
