Regulation of acetyl CoA carboxylase and carnitine palmitoyl transferase-1 in rat adipocytes.
OBJECTIVE
Acetyl CoA carboxylase (ACC) is a key enzyme in energy balance. It controls the synthesis of malonyl-CoA, an allosteric inhibitor of carnitine palmitoyltransferase-1 (CPT-I). CPT-I is the gatekeeper of free fatty acid (FFA) oxidation. To test the hypothesis that both enzymes play critical roles in regulation of FFA partitioning in adipocytes, we compared enzyme mRNA expression and specific activity from fed, fasted, and diabetic rats.


METHODS
Direct effects of nutritional state, insulin, and FFAs on CPT-I and ACC mRNA expression were assessed in adipocytes, liver, and cultured adipose tissue explants. We also determined FFA partitioning in adipocytes from donors exposed to different nutritional conditions.


RESULTS
CPT-I mRNA and activity decreased in adipocytes but increased in liver in response to fasting. ACC mRNA and activity decreased in both adipocytes and liver during fasting. These changes were not caused directly by fasting-associated changes in plasma insulin and FFA concentrations because insulin suppressed CPT-I mRNA and did not affect ACC mRNA in vitro, whereas exogenous oleate had no effect on either. Despite the decrease in adipocyte CPT-I mRNA and specific activity, CO(2) production from endogenous FFAs increased, suggesting increased FFA transport through CPT-I for beta-oxidation.


CONCLUSIONS
Stimulation of FFA transport through CPT-I occurs in both tissues, but CPT-I mRNA and specific activity correlate with FFA transport in liver and not in adipocytes. We conclude that the mechanism responsible for increasing FFA oxidation in adipose tissue during fasting involves mainly allosteric regulation, whereas altered gene expression may play a central role in the liver.
Zang
Yan
Y
Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Wang
Tong
T
Xie
Weisheng
W
Wang-Fischer
Yan-Lin
YL
Getty
Lisa
L
Han
Jianrong
J
Corkey
Barbara E
BE
Guo
Wen
W
D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis / Q000378:metabolism*; D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D002334:Carnitine O-Palmitoyltransferase; D000103:Acetyl-CoA Carboxylase