Tumor necrosis factor-α in sera of obese patients:: Fall with weight loss

被引:443
作者
Dandona, P
Weinstock, R
Thusu, K
Abdel-Rahman, E
Aljada, A
Wadden, T
机构
[1] SUNY Buffalo, Millard Fillmore Hlth Syst, Div Endocrinol Diabet, Buffalo, NY 14209 USA
[2] SUNY Buffalo, Millard Fillmore Hlth Syst, Dept Med, Buffalo, NY 14209 USA
[3] SUNY Syracuse, Dept Med, Endocrine Unit, Syracuse, NY 13210 USA
[4] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA
关键词
D O I
10.1210/jc.83.8.2907
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In view of the recent demonstration that obesity in animals and humans is associated with an increase in tumor necrosis factor-alpha (TNF alpha) expression, that this expression falls with weight loss, and that TNF alpha may specifically inhibit insulin action, the possibility that TNF alpha may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNF alpha concentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin release after glucose challenge. Obese patients (age range: 25-54, weight mean +/- SD: 96.4 +/- 13.8 kg, body mass index: 35.7 +/- 5.6 kg/m(2)) were started on a diet program. The mean weight fell to 84.5 +/- 11.3 (P < 0.0001) and body mass index to 31.3 +/- 4.9 (P < 0.0001). Plasma TNF alpha concentrations were markedly elevated in the obese (3.45 +/- 0.16 pg/mL), when compared with controls (0.72 +/- 0.28 pg/mL), and fell significantly (2.63 +/- 1.40 pg/mL) after weight loss (P < 0.02). The magnitude of insulin release after glucose (75 g) challenge (area under the curve) also fell significantly (P < 0.01) after weight loss. The magnitude of weight loss and fall in TNF alpha were related to basal body weight (r = 0.57, P < 0.001) and basal TNF alpha (r = 0.55, P < 0.001) concentrations, respectively, but not to each other or to the glucose-induced insulin release (area under the curve). We conclude that obesity is associated with increased plasma TNF alpha concentrations, which fall with weight loss. Because circulating TNF alpha may mediate insulin resistance in the obese, a fall in TNF alpha concentrations may contribute to the restoration of insulin resistance after weight loss, Thus, TNF alpha may be an important circulating cytokine, which may provide a potentially reversible mechanism for mediating insulin resistance.
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页码:2907 / 2910
页数:4
相关论文
共 15 条
[1]   TOTAL AND RESTING ENERGY-EXPENDITURE IN OBESE WOMEN REDUCED TO IDEAL BODY-WEIGHT [J].
AMATRUDA, JM ;
STATT, MC ;
WELLE, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (03) :1236-1242
[2]   THE RESPONSE TO LONG-TERM OVERFEEDING IN IDENTICAL-TWINS [J].
BOUCHARD, C ;
TREMBLAY, A ;
DESPRES, JP ;
NADEAU, A ;
LUPIEN, PJ ;
THERIAULT, G ;
DUSSAULT, J ;
MOORJANI, S ;
PINAULT, S ;
FOURNIER, G .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (21) :1477-1482
[3]   INSULIN ACTION AND THE INSULIN SIGNALING NETWORK [J].
CHEATHAM, B ;
KAHN, CR .
ENDOCRINE REVIEWS, 1995, 16 (02) :117-142
[4]   INSULIN RESISTANCE - AN ADAPTATION FOR WEIGHT MAINTENANCE [J].
ECKEL, RH .
LANCET, 1992, 340 (8833) :1452-1453
[5]  
FRIEDENBERG GR, 1988, J CLIN INVEST, V82, P1398
[6]  
GRUNFELD C, 1989, CANCER RES, V49, P2554
[7]   ADIPOSE EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA - DIRECT ROLE IN OBESITY-LINKED INSULIN RESISTANCE [J].
HOTAMISLIGIL, GS ;
SHARGILL, NS ;
SPIEGELMAN, BM .
SCIENCE, 1993, 259 (5091) :87-91
[8]   INCREASED ADIPOSE-TISSUE EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN OBESITY AND INSULIN-RESISTANCE [J].
HOTAMISLIGIL, GS ;
ARNER, P ;
CARO, JF ;
ATKINSON, RL ;
SPIEGELMAN, BM .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (05) :2409-2415
[9]   REDUCED TYROSINE KINASE-ACTIVITY OF THE INSULIN-RECEPTOR IN OBESITY-DIABETES - CENTRAL ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA [J].
HOTAMISLIGIL, GS ;
BUDAVARI, A ;
MURRAY, D ;
SPIEGELMAN, BM .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (04) :1543-1549
[10]   Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance [J].
Hotamisligil, GS ;
Arner, P ;
Atkinson, RL ;
Spiegelman, BM .
DIABETES, 1997, 46 (03) :451-455