Utilization of Ketone Bodies by Adipose Tissue and Its Regulation by Carbohydrate Metabolism

Abstract

In earlier experiments it was found that glucose was able to stimulate the utilization of ketone bodies in eviscerated nephrectomized rats. The present studies were conducted to find whether this action was due to an effect of glucose on the utilization of ketone bodies by adipose tissue. The following results were obtained: 1) Glucose stimulates the uptake of acetoacetate and D-3-hydroxy-butyrate by adipose tissue, but not by diaphragm muscle. Insulin enhances this effect of glucose on adipose tissue. 2) Glucose enhances the conversion of ketone bodies to fatty acids, but causes a decrease in the oxidation of ketone bodies in the Krebs cycle. 3) The incorporation of ¹⁴C-activity from (3-¹⁴C) labelled ketone bodies into glyceride-glycerol and into glycogen via a "cross over" of carbon is diminished by glucose. 4) Insulin stimulates these effects of glucose, but has no effects in the absence of glucose. 5) The effects of glucose on the metabolism of acetate by adipose tissue were similar to those on the metabolism of ketone bodies, but the stimulation of lipogenesis from acetate was much more pronounced than that from ketone bodies. 6) Measurement of the relative incorporation of acetate and ketone bodies into different lipid classes revealed a considerably greater incorporation of ketone bodies into the cholesterol fraction. 7) Glucose shifts the incorporation of acetate or ketone bodies from the phospholipids, mono- and diglycerides to the triglyceride fraction. Insulin enhances this effect but has no effect in the absence of glucose. 8) Citrate, oxalacetate and pyruvate stimulate the uptake of ketone bodies by adipose tissue. 9) Acetoacetate stimulates the uptake of oxygen by adipose tissue in the presence of glucose irrespective of whether there is CO₂ in the gas phase or not. Insulin does not influence the uptake of oxygen in the presence of glucose and acetoacetate. According to these results, adipose tissue is a site for the "peripheral" utilization of ketone bodies. In contrast to muscle, this utilization can be regulated by the utilization of glucose.