Rats were fed a high lard diet or a high glucose diet for 5-7 days. Basal and Concanavalin A (Con A)-stimulated epididymal fat pad pyruvate dehydrogenase (PDH) activities were decreased in fat diet-adapted rats compared to those fed the glucose diet. When adipocyte plasma membranes and mitochondria were coincubated with and without Con A, it was found that the lectin stimulation of PDH activity was lower in preparations from fat-fed rats. These results are comparable to our earlier observations with insulin on adipose tissue PDH. Spermine also stimulated PDH in whole adipose tissue pieces in both the absence and presence (0.5 mM) of medium glucose. The spermine stimulation of PDH in adipose tissue was decreased in fat-fed rats. In contrast to Con A, spermine failed to stimulate PDH in a cell-free system. This suggests that spermine activation of PDH in adipose tissue does not involve the generation of the second messenger responsible for the effects of insulin and Con A. The hypothesis was further substantiated by the findings that (1) the insulin and spermine effects were additive in whole adipose tissue and also in adipocytes, and (2) the spermine effect on fat cells was not significantly inhibited by protease inhibitors, which abolish the effects of insulin on fat cell PDH. The fat-induced decreases in response to Con A and spermine involve not only an adaptive change in the ability of the plasma membrane to generate the chemical modulator of PDH but are also related to postreceptor events.

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