Effects of Fat Mobilization on Liver Acetate Metabolism

Abstract

In insulin deficiency, release of FFA from adipose tissue and increased mobilization of lipids to the liver are followed by excessive ketone body production and a reduction in the incorporation of C-14 from labeled acetate into fatty acids. These changes in liver metabolism may not be related to insulin lack per se, but rather due to a direct effect of an accumulation of lipids or acyl-CoA esters in the tissue. The effect of lipid mobilization was investigated using dichloroisoproterenol (DCI), an adrenergic blocking agent, which has been shown to raise the plasma FFA level in anesthetized dogs with no significant effect on the blood sugar and no apparent effect on plasma insulin levels. In vitro studies have shown that DCI does stimulate FFA release from adipose tissue of the rat or the dog, at a concentration of 10-5 molar, but will block the release normally produced by catecholamines if the concentration of DCI is 10-3 molar. The rapid and sustained elevation of plasma FFA level obtained in the rat following I.P. injection of DCI (50 mg./kg.) over six hours led to an increase in total liver lipids by about 15 mg./gm. liver weight, a 50 per cent increase in ketone production by liver slices and a rise in blood ketone level. Fatty acid synthesis from 2-C-14 sodium acetate was reduced to 25 per cent of the control. An injection of insulin given to the DCI-treated rats one hour before sacrifice, and sufficient to produce hypo-glycemia, reduced the plasma FFA level to normal, but did not influence incorporation of labeled acetate into fatty acids by the liver slices, or the blood ketone level. The results suggest that mobilization of lipids is sufficient to produce changes in liver metabolism similar to those occurring in acute insulin deficiency.

Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production

“…It was also known that a precursor-product relation ship existed between free fatty acids and ketone bodies. The fact that both were elevated in the blood of ketotic animals understandably led to the view that the rate of ketogenesis was determined primarily by the rate of delivery of free fatty acids to the liver (6)(7)(8)(9). The modulating role of insulin on the two processes was considered to be exerted chiefly at the level of adipose tissue.…”

The role of ketogenesis in the migratory fattening of the northern wheatearOenanthe oenanthe

“…Simultaneously, while fuelling, ketogenesis may act as a floodgate, keeping healthy levels of lipid stores and avoiding obesity-related complications like inflammation [27][28][29][30].…”