Effects of hydrogen peroxide on basal and hormone-stimulated lipolysis in perifused rat fat cells in relation to the mechanism of action of insulin.

S.A Little,C De Haën

doi:10.1016/s0021-9258(19)70390-1

Abstract

Since insulin is known to stimulate intracellular hydrogen peroxide production in rat epididymal fat cells, the effects of exogenous hydrogen peroxide on rates of basal and hormone-stimulated lipolysis were investigated in a perifusion system. H2O2 (60 microM) caused a weak and transient stimulation of basal lipolysis that did not interfere with subsequent activation of lipolysis by hormones. More importantly, lipolysis stimulated submaximally with ritodrine (10(-7) M) or glucagon (10(-9) M) was inhibited by H2O2 in a manner similar to insulin, although slight differences in time course were noted. Ritodrine served as a beta-adrenergic agonist resistant to oxidative destruction by H2O2. The inhibition of lipolysis was reversible upon cessation of perifusion with H2O2. These findings ruled out oxidative destruction of the hormone or cell death as explanations for the antilipolytic effect of H2O2. Like insulin, H2O2 also inhibited 1-methyl-3-isobutylxanthine (4 X 10(-6) M)-stimulated lipolysis, but whereas insulin inhibited lipolysis stimulated by dibutyryl-cAMP (4 X 10(-4) M), H2O2 further enhanced it. These findings add another case to the growing list of insulin effects on adipocytes that can be mimicked by exogenous H2O2, and they hint at a site where the mechanisms of action of the two agents may differ.

Highlights

The effectsof exogenous hydrogen peroxidoen rates of in fixed volumeincubations H z 0 2 appeared to be w) basal and hormone-stimulated lipolysis were investi- antilipolytic (10, l l ), the results were not compelling because gatedinaperifusionsystem
We wanted to study whether H202, like insulin, could reversibly inhibit adrenergically stimulated lipolysis
To rule out simple oxidation of the catechol moiety of the adrenergic agent as theapparently antilipolytic mechanism, a number of non-catechol sympathomimetics were investigated for lipolytic activity and stability to H202

Summary

Introduction

The effectsof exogenous hydrogen peroxidoen rates of in fixed volumeincubations H z 0 2 appeared to be w) basal and hormone-stimulated lipolysis were investi- antilipolytic (10, l l ) , the results were not compelling because gatedinaperifusionsystem. M)-stirndatedli- of H202on rates of lipolysisin perifused fat cells and discusses polysis, but whereas insulin inhibited lipolysis stimu- these effectsin relation to themechanism of action of insulin

Objectives

Methods

Conclusion