Are Leptin and Cytokines Involved in Body Weight Gain During Treatment
With Antipsychotic Drugs?
Primary obesity and AP-induced obesity are complex chronic diseases, and
few factors (except increased appetite and food consumption) have been
definitively shown to cause those conditions. Leptin and TNF-a are critically
involved in BW regulation. Most scientific evidence suggests that the high
serum levels of both hormones observed in obese people are consequences
rather than causes of the disease. However, they impair insulin sensitivity,
which in turn promotes glucose intolerance and cardiovascular diseases.
It is plausible that leptin and TNF-a further impair BW regulation and
indirectly perpetuate obesity. Currently, however, this assertion is only
a matter of speculation. More experimental studies exploring the effects
of leptin and cytokines on BW regulation during AP treatment are required.
Finally, clinical studies on this topic must carefully control for relevant
variables such as sex and BMI.
Implications of Elevated Leptin and TNF-a Serum Levels in Patients With
At present, the most parsimonious conclusion is that the increased serum
levels in leptin and TNF-a in these patients is mainly a direct consequence
of BWG and not a specific phenomenon related to AP treatment. Interestingly,
however, the Melkerson and others study (7) offers the possibility that
some olanzapine-treated patients particularly sensitive to drug-induced
metabolic dysregulation may display high leptin and insulin levels despite
having normal BW. This may be related to insulin resistance, which prevents
BWG and promotes serum glucose increase. Hence, this leptin–BW dissociation
might be observed in patients receiving other APs.
Further studies should assess whether such hormone elevation further impairs
the mechanisms of weight regulation. Converging evidence points to the
role of these cytokines in the development and maintenance of myocardial
infarction (30), hypertension (31), insulin resistance (10), and prostatic
cancer (32). Therefore, excessive BWG and obesity must be prevented or
lessened in the general population and in AP-treated patients.
Funding and Support
This review was funded by a Pfizer fellowship and grant # M-718-01-03-B
from CDCH-T (ULA, Venezuela) to Trino Baptista.
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Manuscript received November 2001, revised, and accepted June 2002.
1 Professor Los Andes University Medical School, Department of Physiology,
Mérida, Venezuela; Visiting scientist, Douglas Hospital Research Centre,
McGill University, Verdun, Québec.
2 Assistant Professor, Douglas Hospital Research Centre, McGill University, Verdun, Québec.
Address for correspondence: Dr T Baptista, PO Box 93, Mérida, 5101-A, Venezuela
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