This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gómez-Ambrosi, J. Articles by Frühbeck, G. Search for Related Content PubMed PubMed Citation Articles by Gómez-Ambrosi, J. Articles by Frühbeck, G.

Leptin Therapy Does Not Affect Inflammatory Markers

Metabolic Research Laboratory (J.G.-A., G.F.), and Departments of Endocrinology (J.S., C.S., G.F.), Surgery (F.R., J.A.C.), and Biochemistry (M.J.G.), Clínica Universitaria de Navarra, University of Navarra, 31008 Pamplona, Spain

Address correspondence to: Javier Gómez-Ambrosi, Metabolic Research Laboratory, Clínica Universitaria de Navarra, University of Navarra, 31008 Pamplona, Spain. E-mail: jagomez{at}unav.es.

To the editor:

We read with great interest the paper by Chan et al. (1) in which the lack of effect of the administration of even supraphysiological doses of leptin on C-reactive protein (CRP) and other inflammatory markers in humans is elegantly shown. Obesity is an inflammatory condition characterized by high circulating concentrations of leptin and CRP. Previous studies analyzing the relationship between leptin and CRP are controversial, as mentioned by the authors (1). Our group (2) and others (3) have previously described that the positive correlation between leptin and CRP is biased by body fat. However, other authors have reported that this correlation is still detected after adjusting for body mass index (BMI) (4) or that exogenous leptin administration slightly increases CRP in overweight and moderately obese men (5). With the aim of shedding more light on the potential effect of leptin on the regulation of CRP concentrations, we measured the circulating concentrations of leptin and CRP in a group of 553 subjects (191 males, 362 females) aged between 18 and 75 yr (mean ± SD, 43 ± 13 yr). Subjects were classified as lean (n = 16), overweight (n = 73), or obese (n = 464) according to their BMI. High sensitivity-CRP was measured using the Tina-quant CRP (Latex) ultrasensitive assay (Roche Diagnostics, Barcelona, Spain). Leptin was quantified by RIA (Linco Research, Inc., St. Charles, MO). Body fat was estimated by air-displacement-plethysmography (Bod-Pod, Life Measurements, Concord, CA). We used Pearson’s correlation coefficient and multiple regression models to test the statistical relations between leptin and CRP. Leptin was highly correlated with CRP (r = 0.144; P < 0.001). However, the significance was lost after adjusting by multivariate analysis for body fat (standardized coefficient for leptin = 0.012; P = 0.833) or BMI (standardized coefficient for leptin = 0.006; P = 0.903), indicating that CRP levels are not regulated by leptin per se. Because our study is the one containing the largest sample size so far, we can conclude that although circulating concentrations of leptin and CRP are highly correlated, this association merely reflects the correlation between CRP and adiposity and that leptin does not directly influence CRP levels. Our results are in agreement with the absence of a causative role of leptin in the etiopathology of obesity-associated inflammation described by Chan et al. (1).

Received March 11, 2005.

References

1. 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]
2. Gómez-Ambrosi J, Salvador J, Páramo JA, Orbe J, de Irala J, Diez-Caballero A, Gil MJ, Cienfuegos JA, Frühbeck G 2002 Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors. Clin Biochem 35:315–320[CrossRef][Medline]
3. van Dielen FM, van’t Veer C, Schols AM, Soeters PB, Buurman WA, Greve JW 2001 Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. Int J Obes Relat Metab Disord 25:1759–1766[CrossRef][Medline]
4. Shamsuzzaman AS, Winnicki M, Wolk R, Svatikova A, Phillips BG, Davison DE, Berger PB, Somers VK 2004 Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 109:2181–2185[Abstract/Free Full Text]
5. Hukshorn CJ, Lindeman JH, Toet KH, Saris WH, Eilers PH, Westerterp-Plantenga MS, Kooistra T 2004 Leptin and the proinflammatory state associated with human obesity. J Clin Endocrinol Metab 89:1773–1778[Abstract/Free Full Text]

This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gómez-Ambrosi, J. Articles by Frühbeck, G. Search for Related Content PubMed PubMed Citation Articles by Gómez-Ambrosi, J. Articles by Frühbeck, G.