Guan et al. reply
We are pleased that our report of TZD induction of adipose glycerol kinase1 has prompted further investigation by other groups. Tordjman et al. recently confirmed our observation that rosiglitazone markedly induces glycerol kinase in mouse adipocytes11. In their correspondence, Tan et al. did not find increased glycerol kinase expression in rosiglitazone-treated human adipocytes or in adipose samples from rosiglitazone-treated type 2 diabetics. It is important to note that in the patients studied by Tan et al., rosiglitazone treatment did not lower plasma levels of NEFAs. This differs from nearly all rodent models, as well as several controlled human trials reporting significant lowering of NEFA levels by rosiglitazone and other TZDs5,12,13. Human responses are likely to be more heterogeneous than those of inbred rodent models. If, as we have hypothesized, adipose glycerol kinase induction is one factor contributing to NEFA lowering by TZDs, then lack of glycerol kinase induction may not be surprising in patient populations in which NEFA levels do not respond to TZDs. Larger studies will be needed to determine the extent to which TZD induction of adipose glycerol kinase is variable in humans, and whether this correlates with reduction in NEFA levels upon TZD treatment.
See A “futile cycle” induced by thiazolidinediones in human adipose tissue? by Tan et al.
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Guan, HP., Lazar, M. Reply to “A “futile cycle” induced by thiazolidinediones in human adipose tissue?”. Nat Med 9, 812 (2003). https://doi.org/10.1038/nm0703-812
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DOI: https://doi.org/10.1038/nm0703-812
