Journal of Lipid Research, Vol. 12, 203-213, March 1971
Copyright © 1971 by Lipid Research, Inc.

Reduction in adipocyte ATP by lipolytic agents: relation to intracellular free fatty acid accumulation

A. Angel , K. S. Desai , and M. L. Halperin

Department of Medicine, University of Toronto, Toronto 181, Canada

Epinephrine, norepinephrine, ACTH, and dibutyryl 3',5'-cyclic AMP reduced adipocyte ATP levels during 60 min incubation; glucose displayed a protective effect. The reduction in adipocyte ATP levels could not be attributed solely to: a direct hormone effect, deficiency in metabolic substrate, activation of adenyl cyclase with ATP consumption, loss of adenine nucleotide from the cell or loss of cells during incubation, lipolytic rate per se, or extracellular accumulation of FFA or glycerol.

To determine whether intracellular FFA accumulation was a causative factor, intracellular FFA levels were measured during hormone-stimulated lipolysis. This was accomplished by using sucrose-U-¹⁴C as a marker for the extracellular space to correct for contamination of cells by extracellular albumin-bound FFA. These experiments showed that the fall in adipocyte ATP correlated with FFA saturation of medium albumin and progressive accumulation of FFA within the adipocyte. Furthermore, the protective effect of glucose noted above was associated with a marked reduction in intracellular FFA as compared to the extracellular FFA pool.

On the basis of these studies, combined with those in the literature, it is concluded that in vitro effects of lipolytic agents on adipocyte ATP levels are the net result of imparied ATP synthesis (uncoupled oxidative phosphorylation) in the face of normal or augmented ATP consumption.

Supplementary key words energy metabolism • metabolic controls • intracellular fatty acid pools • hormone-stimulated lipolysis • epinephrine • norepinephrine • ACTH • dibutyryl 3',5'-cyclic AMP • adipose tissue DNA • sucrose space

Submitted on August 26, 1970
Accepted on November 18, 1970

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