Plasma metabolites and food intake reduction following heparinoid injection in rats

Behavioral and physiological consequences of heparinoid injections, which increase plasma levels of nonesterified fatty acids (NEFA) by releasing lipoproteinlipase into the circulation, were studied in rats, because, according to the lipostatic hypothesis of food intake control, changes in plasma metabolite levels should influence food intake. Subcutaneously injected 55 mg/kg body wt. of the heparinoid Na-pentosanpolysulfate (PPS) significantly reduced feeding in rats with ad lib access to either a high carbohydrate (HC) or a high fat (HF) diet. However, the reduction of food intake in HF-rats exceeded that in HC-rats. Moreover, the food intake reduction following PPS-injections was associated with greater increases in plasma levels of NEFA and free glycerol in HF-rats, whereas PPS increased plasma levels of D-(-)-3-hydroxybutyrate only in HF-rats, and did not alter blood glucose concentrations. Although PPS inhibited blood coagulation, it did not affect the hematocrit. Furthermore, PPS-injections that reduced feeding, failed to produce a conditioned taste aversion in a two bottle preference test. The data therefore strongly suggest that elevated levels of plasma NEFA and/or free plasma glycerol decrease food intake in rats. These metabolites might contribute to a lipostatic mechanism of feeding control.