Disappearance of the cholesterol moiety of an injected chylomicron-containing fraction of chyle from the circulation of the rat*

SUMMARY A chylomicron-containing, low-density lipoprotein fraction of thoracic duct chyle (S, classes 20 and higher) obtained from rats fed either cholesterol-4-C14 or palmitic a~id-1-C~' was injected intravenously into rats. Blood samples were obtained every 5 to 10 min for the first 1.5 hr, and thereafter at intervals of 30 min or longer up to 2.5 or 6.5 hr. The disappearance curves for the labeled cholesterol differed strikingly from those for the labeled triglyceride. The former consisted of three phases: (1) rapid decline, (2) rising, and (3) leveling off. During the first phase, lipid-Cl4 disappeared from the circulation less rapidly after the labeled cholesterol injection t.han after injection of the labeled triglyceride. The percentage of 1i~id-C'~ in the circulation increased about threefold during the.rising phase of the cholesterol curves, and almost all of the terminal p1a~ma-C'~ was present in the higher-density lipoproteins (8, classes less than 20). Disappearance curves derived for rats injected with cholesterol-C" in the form of in vitro-prepared, higher-density plasma lipoproteins (S, classes less than 20) showed a gradual initial decline followed by a leveling off. The following conclusions were drawn from these and other available data: The first phase of the curves for the cholesterol-labeled, chylomicroncontaining chyle fraction results from an initial rapid removal of cholesterol-C14 of chylomicrons accompanied by a slow removal of cholesterol-C14 that has been transferred intravascularly to higher-density lipoproteins. This phase, during which most of the chylomicron-cholesterol-C14 is removed from the circulation, is followed by a period during which labeled free sterol is rapidly recirculated from the liver as higherdensity lipoproteins. The greater proportion of the labeled sterol in the plasma lipoproteins during the terminal phase is derived from the sterol that has been recirculated. The latter first declined rapidly and then more slowly. The rate of disappearance, from whole blood or plasma, of injected, isotopically-labeled, very lowdensity chyle lipoproteins has been studied only insofar as their triglyceride and phospholipid moieties are concerned (14). The disappearance curve for the triglyceride moiety declined rapidly at first and more slowly during its second phase. The disappearance rate of the phospholipid moiety from the circulation was much slower than that of the triglyLeride. Recent observations from this laboratory (5) indicated that the disappearance curves of the cholesterol moiety of a chylomicron-containing fraction of chyle might be more complex than the curves for triglycerides and phospholipids. Consequently, we have compared the disappearance of labeled triglyceride and cholesterol moieties of a lowdensity fraction of chyle from the blood stream of rats. It is shown here that the disappearance curves for the isotopic cholesterol are indeed unique. To assist in the interpretation of these curves, the disappearance from the circulation of a cholesterollabeled lipoprotein fraction of plasma (SI classes of less than 20)) prepared in vitro, was also studied.