Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters - A role for leptin in the anorexia of infection

被引:779
作者
Grunfeld, C
Zhao, C
Fuller, J
Pollock, A
Moser, A
Friedman, J
Feingold, KR
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA USA
[2] ROCKEFELLER UNIV, MED GENET LAB, NEW YORK, NY 10021 USA
[3] ROCKEFELLER UNIV, HOWARD HUGHES MED INST, NEW YORK, NY 10021 USA
关键词
leptin; LPS; TNF; IL-1; anorexia;
D O I
10.1172/JCI118653
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The expression of leptin, the ob gene product, is increased in adipose tissue in response to feeding and energy repletion, while leptin expression decreases during fasting, Infusion of leptin decreases food intake, Because adipose tissue gene expression is regulated by cytokines induced during infection and because infection is associated with anorexia, we tested whether induction of leptin might occur during the host response to infection, Administration of endotoxin (LPS), a model for gram negative infections, induces profound anorexia and weight loss in hamsters, In fasted animals, LPS increased the expression of leptin mRNA in adipose tissue to levels similar to fed control animals, There is a strong inverse correlation between mRNA levels of leptin and subsequent food intake, TNF and IL-1, mediators of the host response to LPS, also induced anorexia and increased levels of leptin mRNA in adipose tissue. As assessed by immunoprecipitation and Western blotting, circulating leptin protein is regulated by LPS and cytokines in parallel to regulation of adipose tissue leptin mRNA, Induction of leptin during the host response to infection may contribute to the anorexia of infection.
引用
收藏
页码:2152 / 2157
页数:6
相关论文
共 46 条
[1]  
BODNAR RJ, 1989, CANCER RES, V49, P6280
[2]   RECOMBINANT MOUSE OB PROTEIN - EVIDENCE FOR A PERIPHERAL SIGNAL LINKING ADIPOSITY AND CENTRAL NEURAL NETWORKS [J].
CAMPFIELD, LA ;
SMITH, FJ ;
GUISEZ, Y ;
DEVOS, R ;
BURN, P .
SCIENCE, 1995, 269 (5223) :546-549
[3]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[4]   Serum immunoreactive leptin concentrations in normal-weight and obese humans [J].
Considine, RV ;
Sinha, MK ;
Heiman, ML ;
Kriauciunas, A ;
Stephens, TW ;
Nyce, MR ;
Ohannesian, JP ;
Marco, CC ;
McKee, LJ ;
Bauer, TL ;
Caro, JF .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (05) :292-295
[5]   EVIDENCE AGAINST EITHER A PREMATURE STOP CODON OR THE ABSENCE OF OBESE GENE MESSENGER-RNA IN HUMAN OBESITY [J].
CONSIDINE, RV ;
CONSIDINE, EL ;
WILLIAMS, CJ ;
NYCE, MR ;
MAGOSIN, SA ;
BAUER, TL ;
ROSATO, EL ;
COLBERG, J ;
CARO, JF .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2986-2988
[6]   THE ROLE OF CHOLECYSTOKININ IN INTERLEUKIN-1-INDUCED ANOREXIA [J].
DAUN, JM ;
MCCARTHY, DO .
PHYSIOLOGY & BEHAVIOR, 1993, 54 (02) :237-241
[7]   INDUCTION OF OB GENE-EXPRESSION BY CORTICOSTEROIDS IS ACCOMPANIED BY BODY-WEIGHT LOSS AND REDUCED FOOD-INTAKE [J].
DEVOS, P ;
SALADIN, R ;
AUWERX, J ;
STAELS, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (27) :15958-15961
[8]   INTERLEUKIN-1, ANOREXIA, AND DIETARY FATTY-ACIDS [J].
DINARELLO, CA ;
ENDRES, S ;
MEYDANI, SN ;
MEYDANI, M ;
HELLERSTEIN, MK .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 587 :332-338
[9]   CYTOKINES INDUCE CATABOLIC EFFECTS IN CULTURED ADIPOCYTES BY MULTIPLE MECHANISMS [J].
DOERRLER, W ;
FEINGOLD, KR ;
GRUNFELD, C .
CYTOKINE, 1994, 6 (05) :478-484
[10]   EVIDENCE FOR A DIRECT CENTRAL ANORECTIC EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA IN THE RAT [J].
FANTINO, M ;
WIETESKA, L .
PHYSIOLOGY & BEHAVIOR, 1993, 53 (03) :477-483