Submitted on July 2, 2004
Accepted on October 7, 2004
Effects of Yo-yo Diet, Caloric Restriction, and Olestra on Tissue Distribution of Hexachlorobenzene
Ronald J. Jandacek1*, Nicole Anderson1, Min Liu1, Shuqin Zheng1, Qing Yang1, and Patrick Tso1
1 Department of Pathology and Laboratory Medicine, University of Cincinnati School of Medicine, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: Ronald.Jandacek{at}uc.edu.
Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal
tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through
caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other
tissues. We have studied the reversibility of this process in mice that followed a regimen of body
weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo
diet regimen"). We measured the distribution of orally gavaged 14C-hexachlorobenzene,
which is sparingly metabolized. We found that weight cycling has different effects in different
organs. Continued weight loss resulted in a 3-fold increase of 14C amount and concentration in
the brain. After weight regain, 14C in the brain decreased but then increased again after a second
weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue
without changing the total amount in that tissue. Weight loss and regain resulted in an increase
of 14C in the liver that reflected an increase of fat in the liver. The regimen of weight gain and
loss was repeated in mice gavaged with 14C-hexachlorobenzene, with one group receiving the
non-absorbable fat, olestra, in the diet. Combined dietary olestra and caloric restriction caused a
30-fold increase in the rate of excretion of 14C relative to an ad lib diet or a reduced caloric alone.
The distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by
dietary olestra.
