Sistema factor de necrosis tumoral y leptina en la enfermedad celíaca

Blanco Quirós, A.; Arranz Sanz, E.; Garrote Adrados, J.A.; Oyágüez Ugidos, P.; Calvo Romero, C.; Alonso Franch, M.

doi:10.1016/S1695-4033(01)77666-7

Article information

Objetivo

Los enfermos celíacos presentan malnutrición y una gran anorexia. La leptina es un importante factor anorexígeno estrechamente relacionado con el índice de masa corporal (IMC). El objetivo fue estudiar la leptina sérica en la enfermedad celíaca y su posible acción sobre el apetito, compararla y relacionarla con el factor de necrosis tumoral (TNF), que tiene funciones similares.

Métodos

La leptina y el receptor I de TNF (TNF-R-I) se midieron mediante enzimoinmunoanálisis (ELISA). Se analizaron 65 sueros de enfermos celíacos (28 varones y 37 mujeres). En todos los casos se practicó simultáneamente biopsia intestinal y se determinaron anticuerpos antiendomisio. Estaban en actividad 29 casos y 36 en remisión.

Resultados

Los valores de leptina estaban disminuidos en la fase de actividad de la enfermedad celíaca (p = 0,002), lo que no apoya su participación sobre la anorexia y la desnutrición del paciente celíaco. Durante la remisión de la enfermedad celíaca la leptina se relaciona con el IMC (p = 0,001), pero en la fase activa se rompe esta relación habitual. En la fase aguda también se rompe la diferencia entre sexos, y son similares los valores en varones y mujeres. El TNF-R-I se detectó en todos los sueros y mostró una elevación significativa durante la fase aguda (p = 0,0003) lo que parece indicar una activación del sistema TNF en la enfermedad celíaca.

Conclusiones

La leptina está disminuida durante la fase activa de la enfermedad, y se pierde su habitual correlación con el IMC y el sexo femenino. Los resultados señalan que no participa en la anorexia y la desnutrición de la enfermedad celíaca y, sin embargo, sí podría hacerlo el sistema TNF.

Palabras clave:

Enfermedad celíaca

Índice de masa corporal

Leptina

Factor de necrosis tumoral

Anorexia

Objective

Patients with coeliac disease (CD) present anorexia and malnutrition. Leptin is a significant anorexigenic factor, with a close relationship to the body mass index. The aims of this study were to asses serum leptin levels in CD and their possible influence on appetite, as well as to compare and relate leptin with tumor necrosis factor (TNF) activity, which has similar functions.

Methods

Leptin and TNF receptor-1 (TNFr-1) were measured by enzyme-linked immunosorbent assay. Sixty-five serum samples from patients with CD (28 boys and 37 girls) were analyzed. In all patients, small bowel biopsy and anti-endomysium determination were performed simultaneously. Twenty-nine patients presented active CD and 36 were in remission.

Results

Leptin concentrations were reduced in active CD (p = 0.002). In patients in remission, leptin was related to the body mass index (p = 0.001), but this correlation was not found during the active phase of the disease. Contrary to normal differences between sexes, in active CD leptin levels were similar in boys and girls. TNFr-1 was found in all serum samples and levels were statistically higher in patients with active CD (p = 0.0003), suggesting that the TNF system is activated in this disease.

Conclusions

Leptin concentrations were reduced in active CD, but we did not find the usual positive correlation with body mass index and higher concentrations in girls. These results suggest that leptin does not contribute to anorexia and failure to thrive in patients with CD; in contrast, the TNF system might be involved.

Key words:

Coeliac disease

Body mass index

Leptin

Tumor necrosis factor

Anorexia

Full text is only aviable in PDF

Bibliografía

[1.]

M. Ulshen.

Enteropatía sensible al gluten. Enfermedad celíaca.

Tratado de Pediatría de Nelson, 15.ª ed, pp. 1377-1379

[2.]

A.K. Abbas, A.H. Lichtman, J.S. Pober.

Inmunología celular y molecular.

3.ª ed, Interamericana, (1999),

[3.]

R. Callard, A. Gearing.

The cytokines. Facts Book.

Academic Press, (1994),

[4.]

S. Furukawa, T. Matsubara, Y. Umezawa, K. Okumura, K. Yabuta.

Serum levels of p60 soluble tumor necrosis factor receptor during acute Kawasaki disease.

J Pediatr, 124 (1994), pp. 721-725

Medline

[5.]

J. Auwerx, B. Staels.

Leptin. Lancet, 351 (1998), pp. 737-742

[6.]

A.G. Hoppin, L.M. Kaplan.

The leptin era: new insight into the mechanisms of body weight homeostasis.

J Pediatr Gastroenterol Nutr, 29 (1999), pp. 250-264

Medline

[7.]

R.V. Considine, M.K. Sinha, M.L. Heiman, A. Kriauciunas, T.W. Stephens, M.R. Nyce, et al.

Serum immunoreactive-leptin concentrations in normal-weight and obese humans.

N Engl J Med, 334 (1996), pp. 292-295

http://dx.doi.org/10.1056/NEJM199602013340503 | Medline

[8.]

R.S. Ahima, D. Prabakaran, C. Mantzoros, D. Qu, M. Lowell, E. Maratos-Flier, et al.

Role of leptin in the neuroendocrine response to fasting.

Nature, 382 (1996), pp. 250-252

http://dx.doi.org/10.1038/382250a0 | Medline

[9.]

A. Bado, S. Levasseur, S. Attoub, S. Kermorgant, J.P. Laigneau, M.N. Bortoluzzi, et al.

The stomach is a source of leptin.

Nature, 394 (1998), pp. 790-793

http://dx.doi.org/10.1038/29547 | Medline

[10.]

A. Ballinger.

Gastric leptin.

Gut, 44 (1999), pp. 153-154

Medline

[11.]

I. Sobhani, A. Bado, C. Vissuzaine, M. Buyse, S. Kermorgant, J.P. Laigneau, et al.

Leptin secretion and leptin receptor in the human stomach.

Gut, 47 (2000), pp. 178-183

Medline

[12.]

D. Borowitz.

The interrelationship of nutrition and pulmonary function in patients with cystic fibrosis.

Curr Opin Pulm Med, 2 (1996), pp. 457-461

Medline

[13.]

H. Winter, T.I. Chang.

Gastrointestinal and nutritional problems in children with immunodeficiency and AIDS.

Pediatr Clin North Am, 43 (1996), pp. 573-590

Medline

[14.]

A.G. Hoppin, L.M. Kaplan.

The leptin era: new insight into mechanisms of body weight homeostasis.

J Pediatr Gastroenterol Nutr, 29 (1999), pp. 250-264

Medline

[15.]

T.G. Kirchgessner, K.T. Uysal, S.M. Wiesbrock, M.W. Marino, G.S. Hotamisligil.

Tumor necrosis factor-alpha contribute to obesity-related hyperleptinemia by regulating leptin release from adipocytes.

J Clin Invest, 100 (1997), pp. 2777-2782

http://dx.doi.org/10.1172/JCI119824 | Medline

[16.]

G.A. Spinas, U. Keller, M. Brockhaus.

Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia.

J Clin Invest, 90 (1992), pp. 533-536

http://dx.doi.org/10.1172/JCI115891 | Medline

[17.]

F. Arnalich, J. Lopez, R. Codoceo, M. Jiménez, R. Madero, C. Montiel.

Relationship of plasma leptin to plasma cytokines and human survival in sepsis and septic shock.

J Infect Dis, 180 (1999), pp. 908-911

http://dx.doi.org/10.1086/314963 | Medline

[18.]

D.J. Torpy, S.R. Bornstein, G.P. Chrousos.

Leptin and interleukin- 6 in sepsis.

Horm Metab Res, 30 (1998), pp. 726-729

http://dx.doi.org/10.1055/s-2007-978967 | Medline

[19.]

G.L. Carlson, M. Saeed, R.A. Little, M.H. Irving.

Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis.

Am J Physiol, 276 (1999), pp. E658-E662

Medline

[20.]

S.R. Bornstein, J. Licinio, R. Tauchnitz, L. Engelmann, A.B. Negrao, P. Gold, et al.

Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion.

J Clin Endocrinol Metab, 83 (1998), pp. 280-283

http://dx.doi.org/10.1210/jcem.83.1.4610 | Medline

[21.]

E. Merabet, S. Dagogo-Jack, D.W. Coyne, S. Klein, J.V. Santiago, S.P. Hmiel, et al.

Increased plasma leptinconcentration in end-stage renal disease.

J Clin Endocrinol Metab, 82 (1997), pp. 847-850

http://dx.doi.org/10.1210/jcem.82.3.3817 | Medline

[22.]

E. Ravussin, R.E. Pratley, M. Maffei, H. Wang, J.M. Friedman, P.H. Bennett, et al.

Relatively low plasma leptin concentrations precede weight gain in Pima Indians.

Nat Med, 3 (1997), pp. 238-240

Medline

[23.]

P. Trayhurn, M.E.A. Thomas, J.S. Duncan, V.D. Rayner.

Effect of fasting and refeeding on ob gene expression in white adipose tissue of lean and (ob/ob) mice.

FEBS Lett, 368 (1995), pp. 488-490

Medline

[24.]

H. Vidal, D. Auboeuf, P. De Vos, B. Staels, J.P. Riov, J. Auwerx, et al.

The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue.

J Clin Invest, 98 (1996), pp. 251-255

http://dx.doi.org/10.1172/JCI118786 | Medline

[25.]

K.J. Ellis, M. Nicolson.

Leptin levels and body fatness in children: effects of gender, ethnicity and sexual development.

Pediatr Res, 42 (1997), pp. 484-488

http://dx.doi.org/10.1203/00006450-199710000-00010 | Medline

[26.]

V. Puigdevall Gallego, C. Laudo Pardos, N.A. Ferrández Longas.

Leptina y pubertad.

An Esp Pediatr, 49 (1998), pp. 561-567

Medline

[27.]

R.V. Garcia Mayor, M.A. Andrade, M. Rios, M. Lage, C. Dieguez, F.F. Casanueva.

Serum leptin in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones and puberty.

J Clin Endocrinol Metab, 82 (1997), pp. 2849-2855

http://dx.doi.org/10.1210/jcem.82.9.4235 | Medline

[28.]

L. Gomez, A. Carrascosa, D. Yeste, N. Potau, S. Rique, P. Ruiz-Cuevas, et al.

Leptin values in placental cord blood of human newborns with normal intrauterine growth after 30-42 weeks of gestation.

Horm Res, 51 (1999), pp. 10-14

http://dx.doi.org/23306 | Medline

[29.]

E. Carro, R. Senaris, R.V. Considine, F.F. Casanueva, C. Dieguez.

Regulation of in vivo growth hormone secretion by leptin.

Endocrinology, 138 (1997), pp. 2203-2206

http://dx.doi.org/10.1210/endo.138.5.5238 | Medline

[30.]

K. Clement, C. Vaisse, N. Lahlou, S. Cabrol, J. Pelloux, D. Cassuto, et al.

A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction.

Nature, 392 (1998), pp. 398-401

http://dx.doi.org/10.1038/32911 | Medline

[31.]

M. Barbier, C. Cherbut, A.C. Aube, H.M. Blottiere, J.P. Galmiche.

Elevated plasma leptin concentrations in early stages of experimental intestinal inflammation in rats.

Gut, 43 (1998), pp. 783-790

Medline

[32.]

A. Ballinger.

Divergency of leptin response in intestinal inflammation.

Gut, 44 (1999), pp. 588-589

Medline

[33.]

V. Mohamed-Ali, S. Goodrick, K. Bulmer, J.M.P. Holly, J.S. Yudkin, S.W. Coppack.

Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo.

Am J Physiol, 277 (1999), pp. E971-E975

Medline

[34.]

R. Faggioni, J. Jones Carson, D.A. Reed, C.A. Dinarello, K.R. Feingold, C. Grunfeld, et al.

Leptin-deficient (Ob/ob) mice are protected from T cell mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18.

Proc Natl Acad Sci USA, 97 (2000), pp. 2367-2372

http://dx.doi.org/10.1073/pnas.040561297 | Medline

[35.]

M. Bullo Bonet, P. García Lorda, J.M. Argilés, J. Salas-Salvadó.

Papel del factor de necrosis tumoral en el control de las reservas grasas y la obesidad.

Med Clin, 114 (2000), pp. 624-630

Este trabajo ha sido parcialmente financiado por Pharmacia Spain, S.A.

Indexed in:

Follow us:

Indexed in:

Follow us:

Subscribe to our newsletter