Studies on the Metabolic Effects Induced in the Rat by a High‐Fat Diet

Rats were fed from weaning during 3–4 weeks a high fat carbohydrate‐poor diet. Control groups received a diet in which fat was completely replaced by starch in the same caloric proportion. The effect of this high‐fat diet on the metabolism of pyruvate in diaphragm in vitro was investigated. Glycogen breakdown and glyceride content of the tissue were also measured. Fat diet was shown to induce a reduction in 14 CO 2 production from labelled pyruvate and in the pyruvate uptake. Acetate oxidation was found to be unchanged after fat feeding. This gives evidence for an inhibition of the pyruvate dehydrogenase reaction in diaphragm from fat‐fed rats. The breakdown of glycogen during either an incubation in vitro or a 24‐h fast was significantly reduced in diaphragm from fat‐fed rats. Diaphragm glycerides were found to be increased four‐fold by fat diet. Examination by light‐microscopy of muscle sections have shown that glycerides were present in the muscle fibre and not in adipose tissue cells in the preparation. Inhibition of the oxidation of fatty acids by 2‐bromostearate was shown to reverse completely the impairment of pyruvate metabolism and to stimulate glycolysis. In diaphragm from carbohydrate‐fed rats 2‐bromostearate induced no significant effect on carbohydrate metabolism. Similar results were obtained with glucose as substrate. Rats were fed the high‐fat diet and then the high‐carbohydrate one for a few days. This change of diet was shown to induce a rapid reversal of the inhibition of glucose oxidation in diaphragm in vitro. These results indicate that the impairment of carbohydrate metabolism in diaphragm from fat‐fed rats is probably due to an increased oxidation of fatty acids as observed in muscle from alloxan‐diabetic or starved rats rather than to enzymatic adaptations.