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Fat cell hypertrophy occurs in most forms of obesity. In the obese Zucker rat, fat cell hypertrophy and increased lipoprotein lipase activity (LPL) are the earliest known signs of obesity. We studied the regulation of fat cell size in the obese Zucker rat by measuring changes in fat cell LPL activity and lipolysis in response to an overnight fast in 6- and 14-wk-old lean and obese rats. At both ages, fed obese rats had significantly increased fat cell size, LPL activity, and basal glycerol release in three adipose tissue depots compared to fed lean rats. Obese rats decreased LPL activity in response to fasting, but levels always remained equal to or greater than those in fed lean rats. Obese rats also showed a reduced lipolytic response to fasting. Thus, the obese rat after an overnight fast could not produce a coordinated response to fasting similar to the lean rat, and its homeostatic adjustments to this mild stimulus favored preservation of its enlarged fat cell size.
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