Xanthine oxidase in adipose tissue: potential effects on lipolytic activity [proceedings].

The products of the activity of xanthine oxidase (EC 1.2.3.2) include such reactive substances as H,O,, singlet oxygen and the superoxide and hydroxyl free radicals (KeUogg & Fridovich, 1975), which are currently receiving considerable attention not only because they lead to the formation of lipid hydroperoxides, but also because the latter may promote the formation of prostaglandins (Hemler et al., 1979) and the free radicals themselves may stimulate cyclic GMP synthesis (Mittal & Murad, 1977). It has been shown that xanthine oxidase is present in isolated adipocytes and that it can oxidize the appreciable quantity of purine derivatives released during their incubation in KrebsRinger bicarbonate buffer containing bovine serum albumin (Fain, 1979; M. F. Grahn, J. E. Souness & J. I. Davies, unpublished work). This activity is clearly a potential source of H20, and its free-radical relatives. One mode of action that is open to the purine-related substrates of xanthine oxidase was discovered by Raben & Matsuzaki (1966), who showed that, while diminishing the lipolytic response to L-adrenaline, adenosine, inosine and hypoxanthine added to incubation media containing adiposetissue pieces also enhanced the degradation of the hormone. Both of these effects were reversed by allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), an inhibitor of xanthine oxidase. it became apparent that the degradation of the hormone by products of xanthine oxidase activity cannot adequately account for the effects of purine derivatives on lipolysis when it was shown that these substances also inhibit the lipolytic action of corticotropin (Davies, 1968). However, a more general antilipolytic effect might be expected if the free radicals generated by xanthine oxidase cause changes, not only in the hormone, but also in its target cell. Such changes in adipocyte properties caused by exposure to H,O, have been depicted as ‘insulin-like’ effects (Czech, 1977). Table 1 shows that a combination of xanthine oxidase and xanthine, a substrate of the enzyme, has a potent inhibitory action against the lipolytic response of isolated rat adipocytes to