Lack of Uptake and Oxidation of Chylomicron Triglyceride to Carbon Dioxide and Ketone Bodies by the Perfused Rat Liver

Abstract

FATTY acids concerned with supplying the caloric requirements of the body are transported in the blood primarily as free fatty acids (FFA) or as triglyceride fatty acids (TGFA). The liver is thought to play a central part in the metabolism of both chemical forms¹. Investigations have shown that injected FFA labelled with carbon-14 are taken up by the liver², where they may be catabolized by β-oxidation to carbon dioxide or ketone bodies³, or be synthesized into TGFA, which give rise to the very-low-density (d < 1.006) lipoproteins of the plasma². Chylomicron-TGFA labelled with carbon-14 are also reported to be taken up by the liver⁴ and to be oxidized to carbon dioxide or ketone bodies in certain experimental conditions³. However, previous experiments in vivo have demonstrated that the magnitude of ketogenesis in fat-fed rats is not related to the extent of the influx of chylomicrons⁵ but rather to the level of circulating FFA⁶. In perfused livers from fasted rats, Morris³ found that 75 per cent of chylomicron-TGFA were removed from the perfusate and more than 20 per cent oxidized to carbon dioxide and ketone bodies in 4 h. Similarly, Rodbell et al.⁷ reported 25 per cent uptake and 2 per cent oxidation of a triglyceride emulsion in 2 h. As these authors used heparin (a known activator of lipoprotein lipase) in their standard preparations, the extent to which hydrolysis of the infused TGFA to FFA was responsible for these significant rates of uptake and oxidation remains unknown.