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Food Lipids: Chemistry, Nutrition, and Biotechnology

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monier (252) suggested that in certain conditions there might be a ‘‘maximum cell<br />

size’’ which is similar regardless of animal sex or adipose depot site. Thus, the greater<br />

degree of hyperplasia observed in the perirenal compared with other fat depots in<br />

response to high-fat feeding may be due to the fact that cells of this depot are already<br />

near-maximal in size [for review, see (259)]. Likewise, Faust et al. (258) advanced<br />

the notion that during the development of obesity in adult rats fed a high-fat diet,<br />

the achievement of some specific mean fat cell size triggers the events that lead to<br />

an increase in adipocyte number. They further suggested that when this ‘‘critical’’<br />

fat cell size is reached, a stimulus for new cell production or differentiation may be<br />

produced.<br />

Several studies indicated that the feeding of a high-fat diet to adult rats leads<br />

to an increase in the incorporation of [ 3 H]thymidine into the DNA of specific adipose<br />

tissue fractions (271,272), providing direct evidence that the diet-induced increase<br />

in fat cell number is indeed a consequence of cellular proliferation. However, a direct<br />

link between an increase in cellular proliferation <strong>and</strong> the release of factors from<br />

adipose tissue triggering this effect has been difficult to demonstrate. For example,<br />

Bjorntorp et al. (273) reported that addition of plasma from either chow-fed or highfat-fed<br />

rats to adipocyte precursors in culture has similar effects on inducing preadipocyte<br />

proliferation <strong>and</strong> differentiation. Likewise, Shillabeer et al. (274) <strong>and</strong> Lau<br />

et al. (275) observed that media conditioned by exposure to mature fat or cells<br />

obtained from adipose tissue influence the proliferation <strong>and</strong> differentiation of cultured<br />

preadipocytes. However, a similar effect on preadipocyte differentiation is observed<br />

with fat from rats fed differing levels <strong>and</strong> types of dietary fat (264). In contrast,<br />

compelling evidence for such a relationship between diet-induced alterations in adipose<br />

tissue cellularity <strong>and</strong> the release or modification of local growth factors from<br />

adipose tissue of high-fat diet–treated animals was obtained in recent studies from<br />

our laboratory (276,277). These studies indicated that changes in adipose cellularity<br />

during the development of obesity in rats fed high-fat diets may be associated with<br />

the appearance of a locally produced factor(s) capable of stimulating adipose cell<br />

proliferation. Specifically, we observed that rats fed high-fat diets have increased<br />

numbers of both very small <strong>and</strong> large cells within their adipose tissue depots <strong>and</strong><br />

that media conditioned by exposure to the fat from these animals significantly increase<br />

the proliferation of preadipocytes in primary culture (276). In addition, we<br />

determined that total tissue content of insulin-like growth factor type I (IGF-I) is<br />

greater in the fat pads of high-fat diet rats as compared with their low-fat diet controls<br />

(277). Furthermore, adipogenic activity in the conditioned media from the high-fat<br />

diet rats could be attenuated through neutralization with an IGF-I antibody (276).<br />

Taken together, these studies support the concept that the enlargement of adipocytes<br />

during the development of diet-induced obesity may lead to the secretion of local<br />

growth factors involved in the regulation of adipose tissue expansion <strong>and</strong> that<br />

IGF-I may be at least partially responsible for this effect (Fig. 2).<br />

D. Cellularity Changes <strong>and</strong> the Reversibility of Obesity<br />

The potential reversibility of obesity induced by high-fat feeding may be dependent<br />

on the duration <strong>and</strong>/or severity of the dietary treatment (258,278,279). For example,<br />

diet-induced obesity is reversed when the animals are returned to a low-fat diet after<br />

16 (278) but not after 30 weeks (279) of high-fat feeding. It has been proposed that<br />

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

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