Effects of pregnancy and exercise on concentrations of the
metabolic markers tumor necrosis factor α and leptin
James F. Clapp III, MD, and Wieland Kiess, MD
Cleveland, Ohio, and Leipzig, Germany
OBJECTIVE: Pregnancy and exercise have opposite effects on fat mass and insulin resistance. We therefore
designed this study to test the hypotheses that exercise during pregnancy alters the pregnancy- associated
increases in the levels of tumor necrosis factor α and leptin and that the changes in tumor necrosis factor α
and leptin concentrations during pregnancy continue to reflect changes in fat mass.
STUDY DESIGN: The levels of tumor necrosis factor α and leptin were measured longitudinally in a control
group of physically active women, a group of women who performed endurance exercises ≥4 times a week
throughout pregnancy, and a group of women who initially performed endurance exercises but then stopped
exercising during midpregnancy. Exercise was monitored, and longitudinal estimates of maternal total mass
and fat mass were obtained.
RESULTS: Tumor necrosis factor α levels were lower during pregnancy in the women who exercised, and
the same was true for leptin levels. When women stopped exercising, however, both tumor necrosis factor α
and leptin concentrations rose at rates comparable to those seen in the physically active control group.
Changes in leptin concentration but not those in tumor necrosis factor α concentration correlated with the
pregnancy-associated increases in total body and fat mass.
CONCLUSIONS: Regular weight-bearing exercise during pregnancy suppresses the pregnancy-associated
changes normally seen in both tumor necrosis factor α and leptin. The decrease in leptin reflects decreased
fat accretion, and we speculate that the changes in tumor necrosis factor α may reflect a change in insulin
resistance. (Am J Obstet Gynecol 2000;182:300-6.)
Key words: Exercise, fat mass, leptin, pregnancy, tumor necrosis factor α
The inflammatory cytokine tumor necrosis factor α
(TNF-α) has been shown to be produced in both adipose
tissue and skeletal muscle and appears to modulate in-
sulin resistance in both tissues by inhibiting insulin re-
ceptor tyrosine kinase activity through serine phosphory-
lation of insulin receptor substrate.
TNF-α messenger ribonucleic acid is overly expressed in
decidua and placenta, and TNF-α is thought to play a
major role in multiple reproductive events, such as pla-
centation and the onset of labor.
Late pregnancy is also characterized by increases in
both insulin resistance and circulating levels of TNF-α.
In the nonpregnant state regular exercise decreases in-
sulin resistance, but the effects of exercise on TNF-α lev-
els are relatively unstudied and may be gender specific.
Regular weight-bearing exercise during late pregnancy
decreases weight gain and fat accretion, but its effects on
insulin resistance and TNF-α levels are unknown.
Leptin, the product of the ob gene,
is produced in
adipose tissue and correlates with both indexes of body
fat and TNF-α expression.
In addition, leptin levels
fluctuate with acute changes in energy intake and weight,
and in rodents leptin alters both appetite and energy ex-
penditure by means of hypothalamic receptors.
During pregnancy the placenta also produces leptin,
and maternal leptin levels rise dramatically and are cor-
related with both indexes of body fat and resting meta-
In the nonpregnant state regular exercise
is associated with a decrease in circulating leptin levels,
but the relationship of leptin with exercise type and asso-
ciated changes in fat mass is controversial.
tionships among exercise, changes in fat mass, and
changes in leptin levels have not been studied during
The purpose of this study was to examine the relation-
ship between exercise and the circulating levels of TNF-α
and leptin before and during pregnancy to determine
From the Departments of Reproductive Biology and Obstetrics and
Gynecology and the Schwartz Center for Metabolism and Nutrition,
Case Western Reserve University at MetroHealth Medical Center, and
the Children’s Hospital, University of Leipzig.
Supported by National Institutes of Health grants HD21268,
HD21109, and RR00080 to the Schwartz Center for Metabolism and
Nutrition, the Alexander von Humboldt Foundation, and MetroHealth
Received for publication April 15, 1999; revised July 27, 1999; accepted
September 1, 1999.
Reprint requests: James F. Clapp III, MD, Department of Obstetrics and
Gynecology, MetroHealth Medical Center, 2500 MetroHealth Dr,
Cleveland, OH 44109.
Copyright © 2000 by Mosby, Inc.
0002-9378/2000 $12.00 + 0 6/1/103093