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Authors’ Response: Leptin Therapy Does Not Affect Inflammatory Markers

Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215

Address correspondence to: Christos S. Mantzoros, M.D., D.Sc., Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215. E-mail: cmantzor{at}bidmc.harvard.edu.

To the editor:

We thank Gómez-Ambrosi et al. (1) for their comment. The role of leptin in the development of the proinflammatory state associated with obesity had initially been postulated on the basis of the high leptin levels observed in obesity and subsequently on the association between leptin levels and several inflammatory markers shown in observational studies. Importantly, recently performed, appropriately designed observational studies of sufficient power, which also adjust for relevant factors such as fat mass, such as the one by Gómez-Ambrosi et al. (1), demonstrate that the correlation between leptin and C-reactive protein may reflect the underlying relationship between leptin and body fat, rather than an independent effect of leptin per se. Although cross-sectional studies provide important information and can raise hypotheses for further investigation, they do not fully exclude the possibility of leptin being in the causal pathway of the obesity-hyperleptinemia-proinflammatory state. Thus, interventional studies using administration of recombinant human leptin (r-metHuLeptin) to achieve a broad range of supraphysiological to pharmacological leptin levels in normal-weight and obese, healthy and diabetic subjects are needed to fully explore the role of leptin in possibly mediating, fully or in part, the association of obesity with a proinflammatory state. We have thus performed an interventional study employing r-metHuLeptin (2) to directly test this hypothesis and found no evidence to support an etiopathogenic role for leptin in altering levels of the proinflammatory markers studied (2). Additional studies using similar interventional design(s) are warranted to fully elucidate the effect of high leptin levels on markers of endothelial dysfunction and cardiovascular risk, e.g. thrombotic factors (fibrinogen, plasminogen activator inhibitor-1, etc.) as well as intima-media thickness, endothelial function, and vascular reactivity.

Received March 24, 2005.

References

1. Gómez-Ambrosi J, Salvador J, Silva C, Rotellar F, Gil MJ, Cienfuegos JA, Frühbeck G 2005 Leptin therapy does not affect inflammatory markers. J Clin Endocrinol Metab 90:3803 (Letter)[Free Full Text]
2. Chan JL, Bullen J, Stoyneva V, DePaoli AM, Addy C, Mantzoros CS 2005 Recombinant methionyl human leptin administration to achieve high physiologic or pharmacologic leptin levels does not alter circulating inflammatory marker levels in humans with leptin sufficiency or excess. J Clin Endocrinol Metab 90:1618–1624[Abstract/Free Full Text]

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