AJP - Endocrinology and Metabolism, Vol 258, Issue 2 E320-E328, Copyright © 1990 by American Physiological Society
Defective metabolic effects of norepinephrine and insulin in obese Zucker rat brown adipose tissue
A. Marette, A. Geloen, A. Collet and L. J. Bukowiecki
Department of Physiology, Laval University, Medical School, Quebec, Canada.
The effects of insulin and norepinephrine on oxygen consumption, lipolysis,
and glucose transport were investigated in adipocytes isolated from brown
adipose tissue (BAT) of adult (4-5 mo) lean (Fa/?) and obese (fa/fa) Zucker
rats. Total BAT protein content and cytochrome oxidase activity were
similar in both phenotypes, suggesting that obese rats have a normal
mitochondrial content. Light and electron micrographs revealed that brown
adipocytes from obese rats contained very large multilocular triglyceride
droplets, but their mitochondrial ultrastructure was normal.
Norepinephrine, when added in excess (1 microM), stimulated brown adipocyte
respiration 8-10 times above basal levels both in lean and obese animals.
However, dose-response experiments disclosed that the 50% effective
concentration (EC50) was significantly higher in cells isolated from obese
rats compared with lean ones (EC50 115 vs. 43 nM, P less than 0.05). The
lipolytic sensitivity to norepinephrine was also reduced in adipocytes
isolated from obese animals (EC50 83 vs. 12 nM, P less than 0.05). Addition
of dibutyryl adenosine 3',5'-cyclic monophosphate to respiring obese rat
brown adipocytes restored to normal the defective response to
norepinephrine, suggesting that the reduction in catecholamine sensitivity
resulted from a deactivation of the receptor-adenylate cyclase complex. On
the other hand, the antilipolytic and antithermogenic actions of
physiological concentrations of insulin were significantly reduced in obese
BAT cells. The sensitivity and responsiveness of obese rat brown adipocytes
for insulin-stimulated glucose transport were also markedly decreased (EC50
1 vs. 0.3 nM, P less than 0.05; maximal velocity 3-fold vs.
7-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
