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D K Spady

Publications and source records attributed to D K Spady.

At least 55 records · Page 3Linked to original sources
PubMed1989

Interaction of aging and dietary fat in the regulation of low density lipoprotein transport in the hamster.

These studies were undertaken to examine the effect of aging on low density lipoprotein (LDL) metabolism in the male hamster. When the hamsters were maintained on a low-cholesterol, low-triglyceride diet, rates of LDL transport in the various tissues of the body and plasma LDL-cholesterol concentrations remained constant over the entire life span (1-24 months) of the hamster. In contrast, rates of de novo cholesterol synthesis fell 50-97% in the various tissues of the body during the transition from rapid body growth in the young animal to the stable adult size. Thus, changes in tissue requirements for cholesterol over the life span of these animals were met by an appropriate adjustment in the rate of de novo synthesis rather than by alterations in LDL transport. When animals were fed a diet enriched in cholesterol and saturated triglycerides, rates of LDL production increased, total body LDL receptor activity was suppressed, and plasma LDL-cholesterol levels rose. Older animals, however, were not more susceptible than young animals to the detrimental effects of these dietary fats. These studies support the view that aging per se has not effect on LDL transport by the liver or other tissues. Rather, the progressive rise in plasma LDL-cholesterol levels seen in Western man is likely due to the consumption of a diet enriched in cholesterol and saturated triglyceride which increases the LDL-cholesterol production rate and suppresses receptor-dependent LDL transport.

Aging↗
PubMed1988

Interaction of dietary cholesterol and triglycerides in the regulation of hepatic low density lipoprotein transport in the hamster.

These studies report the effects of dietary cholesterol and triglyceride on rates of receptor-dependent and receptor-independent LDL transport in the liver of the hamster. In animals fed diets enriched with 0.1, 0.25, or 1% cholesterol for 1 mo, receptor-dependent LDL transport in the liver was suppressed by 43, 63, and 77%, respectively, and there were reciprocal changes in plasma LDL-cholesterol concentrations. In addition, dietary triglycerides modified the effect of dietary cholesterol on hepatic LDL transport and plasma LDL concentrations so that at each level of cholesterol intake, polyunsaturated triglycerides diminished and saturated triglycerides accentuated the effect of dietary cholesterol. When animals were raised from weaning on diets containing small amounts of cholesterol, the decline in receptor-dependent LDL transport was nearly abolished by the addition of polyunsaturated or monounsaturated triglycerides, but was markedly augmented by the addition of saturated lipids. When animals raised on diets containing cholesterol and saturated triglycerides were returned to the low cholesterol, low triglyceride control diet, hepatic receptor-dependent LDL transport and plasma LDL-cholesterol concentrations returned essentially to normal within 2 wk. Neither receptor-independent LDL transport nor the receptor-dependent uptake of asialofetuin was significantly altered by dietary cholesterol or triglyceride suggesting that the effect of these lipids on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physiochemical properties of hepatic membranes. These studies demonstrate the important role of saturated triglycerides in augmenting the effect of cholesterol in suppressing hepatic LDL receptor activity and elevating LDL-cholesterol levels.

Animals↗
PubMed1987

Laser photocoagulation for the treatment of acute peptic-ulcer bleeding. A randomized controlled clinical trial.

We tested the hypothesis that therapeutic endoscopy using the Nd:YAG (neodymium:yttrium-aluminum-garnet) laser would benefit patients with acute peptic-ulcer bleeding. Over 43 months, 174 patients with active bleeding (n = 32) or stigmata of recent bleeding (n = 142) due to peptic ulcers were randomly assigned during endoscopy to either standard treatment with laser photocoagulation or therapy without photocoagulation. There were no significant differences in a number of outcomes between the group treated with laser photocoagulation and the control group. Continued bleeding or rebleeding was observed in 22 percent of the laser-treated group and in 20 percent of the control group. Urgent surgery was necessary in 16 percent of the laser-treated patients and in 17 percent of the controls. Laser-treated patients spent a mean of 41 hours in the intensive care unit, and controls spent a mean of 32 hours. The mean hospital stay was 12 days in the laser-treated group and 11 days in the control group. One death occurred in each group. When patients with active bleeding were analyzed separately, there was no significant difference in outcome, even though laser photocoagulation stopped active bleeding in 88 percent of cases. Among patients with visible vessels, rebleeding occurred in 5 of 14 (36 percent) who received laser treatment and 2 of 15 (13 percent) who did not. Laser treatment precipitated bleeding in four patients and duodenal perforation in one. We conclude that Nd:YAG-laser photocoagulation does not benefit patients with acute upper gastrointestinal bleeding from peptic ulcers.

Acute Disease↗
PubMed1987

Kinetic characteristics and mechanisms of regulation of receptor-dependent and receptor-independent LDL transport in the liver of different animal species and humans.

In the normal animal and in humans, low-density lipoproteins (LDL) are removed from the plasma by both receptor-dependent and receptor-independent transport mechanisms. Most of the receptor-dependent transport activity is found in the liver, whereas the receptor-independent transport process is widely distributed in many organs. In the steady state the plasma LDL-cholesterol concentration is determined by the rate of LDL production, relative to the rate of LDL removal from the vascular space. This rate of removal in turn is determined by three transport parameters: Jm, the maximal transport rate for the receptor-dependent process in the whole animal; Km, the concentration of LDL-cholesterol in the plasma at which half Jm is achieved; and P, the proportionality constant for the receptor-independent transport process. The values of these parameters are now known for several species, including humans and provide the basis for understanding how the plasma LDL-cholesterol concentration is altered by environmental factors such as aging and diet. With aging, for example, there appears to be no change in the receptor-dependent transport process, and in those situations in which the plasma LDL-cholesterol level rises, this increase appears to be caused by overproduction of LDL. With cholesterol feeding the plasma LDL-cholesterol level rises because of an increase in the LDL production rate coupled with a decrease in the maximal transport rate for the receptor-dependent process. The addition of saturated triglycerides to the diet further suppresses the Jm value, whereas unsaturated lipids enhance the maximal transport rate for LDL and lowers the plasma LDL-cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Role of receptor-independent low density lipoprotein transport in the maintenance of tissue cholesterol balance in the normal and WHHL rabbit.

These studies were undertaken to determine the role of receptor-independent low density lipoprotein (LDL) transport in cholesterol balance across individual tissues and the whole animal. Homologous LDL, which measures total LDL transport, and methylated heterologous LDL, which measures receptor-independent LDL uptake, were cleared from the plasma at very different rates in the NZ control rabbit (3,900 and 1,010 microliter/hr per kg, respectively) whereas in the WHHL rabbit both preparations were cleared at essentially the same rate (approximately 1,070 microliter/hr per kg). Receptor-independent LDL clearance was detected in all tissues of the NZ control rabbit and these varied from 32 (spleen) to less than 0.5 (skeletal muscle) microliter/hr per g. In contrast, receptor-dependent LDL uptake was found in only about half of these same organs. In the WHHL rabbit, the rates of receptor-independent LDL transport were the same as in the NZ control rabbit, but no receptor-dependent uptake was detected. Using these clearance values it was calculated that in the control rabbit nearly 70% of LDL-cholesterol was removed from the plasma by the liver and 89% of this was receptor-mediated. With loss of receptor activity, however, the burden of LDL degradation was shifted away from the liver so that approximately 70% of LDL-cholesterol uptake took place in the extra-hepatic tissues of the WHHL rabbit. Thus, in the normal animal, the primary function of receptor-dependent LDL transport is to promote the rapid uptake and disposal of plasma LDL by the liver. In the absence of such receptor activity, cholesterol balance across most individual organs and the whole animal remains essentially normal and is mediated by the receptor-independent process. Because of the much lower absolute clearance rates manifested by this transport mechanism, however, substantial and predictable elevations in the circulating plasma LDL-cholesterol levels are required to maintain this balance.

Animals↗
PubMed1986

Low density lipoprotein-receptor activity is lost in vivo in malignantly transformed renal tissue.

Mammalian cells can acquire cholesterol through two tightly regulated pathways, namely de novo cholesterol synthesis and receptor-mediated endocytosis of circulating low density lipoprotein (LDL). Malignant cells growing in vitro acquire cholesterol through both mechanisms but the quantitative importance of these pathways to a cancer growing in vivo is not known. Using the Lewis rat renal carcinoma model, this study measured the rate of cholesterol acquisition via both pathways in vivo in both normal and malignant renal tissue. In contrast to normal kidney, after malignant transformation, LDL-receptor activity disappeared entirely and the cancer acquired the cholesterol needed for growth by a 5-fold increase in the rate of cholesterol synthesis.

Adenocarcinoma↗
PubMed1986

Bile acids regulate hepatic low density lipoprotein receptor activity in the hamster by altering cholesterol flux across the liver.

The effect of different bile acids on receptor-dependent and receptor-independent low density lipoprotein (LDL) uptake in the liver and intestine was investigated. When fed at the 0.1% level for three weeks, cholic acid and chenodeoxycholic acid suppressed hepatic cholesterol synthesis in the rat by 80% and 50%, respectively, while ursodeoxycholic acid had no effect. In contrast, hepatic cholesteryl ester levels, rates of hepatic LDL transport, and concentrations of plasma LDL-cholesterol were not affected by bile acid feeding in this species. Cholic acid and chenodeoxycholic acid also suppressed hepatic cholesterol synthesis in the hamster. However, since basal rates of hepatic cholesterol synthesis in this species, as in man, are very low, the absolute reduction in hepatic synthesis could not compensate for the change in hepatic sterol balance induced by bile acid feeding. Hence, in the hamster the feeding of cholic acid and chenodeoxycholic acid increased hepatic cholesteryl ester levels 660% and 39%, respectively, reduced hepatic receptor-dependent LDL uptake by 50% and 32%, respectively, and elevated plasma LDL-cholesterol levels by 160% and 50%, respectively. Ursodeoxycholic acid feeding did not alter any of these processes, and none of the bile acids changed the rate of hepatic receptor-independent LDL transport. In the intestine, none of the bile acids altered rates of cholesterol synthesis or LDL uptake. When cholic acids, chenodeoxycholic acid, or ursodeoxycholic acid was infused continuously for 8 hr in supranormal amounts into control hamsters or rats or into animals pretreated with cholestyramine, there were no changes in LDL transport or any other parameter of hepatic cholesterol metabolism. Thus, these studies indicated that cholic acid and chenodeoxycholic acid have no acute, direct effect on rates of receptor-dependent LDL transport or cholesterol synthesis but do alter these processes indirectly by inducing changes in cholesterol balance across the liver. Ursodeoxycholic acid, in contrast, does not affect these processes either directly or indirectly and so causes no change in plasma LDL levels.

Animals↗
PubMed1986

Kinetic constants for receptor-dependent and receptor-independent low density lipoprotein transport in the tissues of the rat and hamster.

In this study, carried out in the rat and hamster, the receptor-dependent low density lipoprotein (LDL) transport process in each organ was characterized in terms of its maximal uptake rate (Jm) and Michaelis constant (Km), while the rate of receptor-independent uptake was defined in terms of its proportionality constant (P). The highest Jm values of 50-126 micrograms/h per g were found in the liver and endocrine glands in both species and receptor-dependent uptake also was detected in other organs like spleen, kidney, and intestine. The Km values were essentially the same in all of the organs and equaled approximately 90 mg/dl in both species. The receptor-independent uptake constants also were similar in the two species and were highest in the spleen, liver, and intestine. From these values for Jm, Km, and P, it was possible to construct theoretical curves that predict the plasma LDL-cholesterol concentration and fractional catabolic rate given any alteration in LDL-cholesterol production or the magnitude of receptor-dependent LDL transport in any organ of the rat or hamster.

Animals↗
PubMed1986

Renal cell carcinoma in the Wistar-Lewis rat: a model for studying the mechanisms of cholesterol acquisition by a tumor in vivo.

Renal adenocarcinoma implanted into isogeneic Wistar-Lewis rats closely resembles human renal cancer. This paper characterizes the tumor's growth rate, metastatic potential, and its light and electron microscopic appearance. Additionally, for the first time, the pathways through which a tumor acquires the cholesterol needed for growth were quantified in vivo. Two 1-mg pieces of renal carcinoma were implanted beneath the renal capsule of 80 Wistar-Lewis rats. Of the implanted tumors 95% "took" and grew rapidly, doubling every 2.6 days initially. Growth slowed, however, to a doubling time of 8.3 days by the fifth wk. Twenty rats underwent surgical resection of the primary tumor 5 wk after implantation. Of these, 85% subsequently developed lung metastases. Histologically, the tumor had a clear-cell appearance due to the presence of large vacuoles, some of which contained glycogen. The esterified cholesterol content of the tumor was 3-fold higher than normal kidney during the initial period of rapid tumor growth and increased to a 14-fold elevation by 12 wk. The normal kidney in vivo had a high rate of uptake of cholesterol carried in low density lipoproteins and a low rate of de novo sterol synthesis. In contrast, the renal carcinoma lost most of its low density lipoprotein uptake activity and, instead, acquired the cholesterol needed for growth by a 5-fold increase in the rate of de novo cholesterol synthesis. This model may prove valuable in both testing therapeutic strategies directed against human renal cancer and understanding the regulation of cholesterol homeostasis in a growing cancer.

Animals↗
PubMed1985

Rates of cholesterol synthesis and low-density lipoprotein uptake in the adrenal glands of the rat, hamster and rabbit in vivo.

The absolute rate of cholesterol acquisition from de novo synthesis and from receptor-dependent and receptor-independent low-density lipoprotein (LDL) uptake was determined in the adrenal glands of the rat, hamster and rabbit under in vivo conditions. The rate of incorporation of [3H]water into cholesterol in the adrenal gland was much higher in the hamster (1727 nmol/h per g) and rabbit (853 nmol/h per g) than in the rat (71 nmol/h per g). Assuming that 23 atoms of 3H are incorporated into the cholesterol molecule during its biosynthesis, the absolute rates of cholesterol synthesis were then calculated to equal 59, 29 and 2.4 micrograms/h per g of adrenal gland in the hamster, rabbit and rat, respectively. Rates of LDL-cholesterol uptake were measured using a primed continuous infusion of [14C]sucrose-labeled homologous LDL (total LDL transport) and methylated human LDL (receptor-independent LDL transport). The rate of total LDL-cholesterol uptake in the adrenal gland was much higher in the rabbit (227 micrograms/h per g) than in the rat (18 micrograms/h per g) or hamster (6 micrograms/h per g). In all three species LDL uptake was mediated largely (greater than 93%) by receptor-dependent mechanisms. In terms of total cholesterol acquisition, the hamster adrenal gland derived 10-times more cholesterol from de novo synthesis than from LDL uptake, whereas the converse was true in the rabbit. Rates of de novo synthesis and LDL-cholesterol uptake were both low in the rat adrenal gland, which is known to derive cholesterol mainly from circulating high-density lipoproteins. Thus, the adrenal gland acquires cholesterol for hormone synthesis from at least three different sources and the quantitative importance of these sources varies markedly in different animal species, including man.

Adrenal Glands↗
PubMed1985

Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster.

The liver plays a key role in the regulation of circulating levels of low density lipoproteins (LDL) because it is both the site for the production of and the major organ for the degradation of this class of lipoproteins. In this study, the effects of feeding polyunsaturated or saturated triacylglycerols on receptor-dependent and receptor-independent hepatic LDL uptake were measured in vivo in the hamster. In control animals, receptor-dependent LDL transport manifested an apparent Km value of 85 mg/dl (plasma LDL-cholesterol concentration) and reached a maximum transport velocity of 131 micrograms of LDL-cholesterol/hr per g, whereas receptor-independent uptake increased as a linear function of plasma LDL levels. Thus, at normal plasma LDL-cholesterol concentrations, the hepatic clearance rate of LDL equaled 120 and 9 microliter/hr per g by receptor-dependent and receptor-independent mechanisms, respectively. As the plasma LDL-cholesterol was increased, the receptor-dependent (but not the receptor-independent) component declined. When cholesterol (0.12%) alone or in combination with polyunsaturated triacylglycerols was fed for 30 days, receptor-dependent clearance was reduced to 36-42 microliter/hr per g, whereas feeding of cholesterol plus saturated triacylglycerols essentially abolished receptor-dependent LDL uptake (5 microliter/hr per g). When compared to the appropriate kinetic curves, these findings indicated that receptor-mediated LDL transport was suppressed approximately equal to 30% by cholesterol feeding alone and this was unaffected by the addition of polyunsaturated triacylglycerols to the diet. In contrast, receptor-dependent uptake was suppressed approximately equal to 90% by the intake of saturated triacylglycerols. As compared to polyunsaturated triacylglycerols, the intake of saturated lipids was also associated with significantly higher plasma LDL-cholesterol concentrations and lower levels of cholesteryl esters in the liver.

Animals↗
PubMed1985

Receptor-independent low density lipoprotein transport in the rat in vivo. Quantitation, characterization, and metabolic consequences.

Receptor-independent low density lipoprotein (LDL) transport plays a critical role in the regulation of plasma cholesterol levels; hence, these studies were done to characterize this process in the tissues of the rat. High rates of receptor-independent clearance were found in the spleen, but other organs, like liver, gastrointestinal tract, and endocrine glands manifested lower clearance rates that varied from 3 to 9 microliter/h per g, while the rates in nervous tissue, muscle, and adipose tissue were less than 1 microliter/h per g. Receptor-dependent uptake was much higher in liver (85 microliter/h per g) and adrenal gland (219 microliter/h per g), but was also low in most other tissues. At normal plasma LDL concentrations, 67% of the receptor-dependent transport in the whole animal was accounted for by LDL uptake in the liver. In contrast, the receptor-independent uptake found in the whole animal took place in many organs, including skeletal muscle (20%), liver (16%), small bowel (15%), skin (10%), and spleen (7%). Furthermore, in liver, the rate of cholesterol synthesis could be varied 11-fold, yet the rate of receptor-independent LDL clearance remained constant at approximately 8 microliter/h per g. When the circulating levels of LDL were systematically increased, receptor-independent LDL clearance also remained constant, so that hepatic LDL-cholesterol uptake by this mechanism increased linearly, from 1 to 20 micrograms/h per g, as the plasma LDL-cholesterol level was increased from 10 to 250 mg/dl. Finally, when equal amounts of LDL-cholesterol were delivered into the liver by either the receptor-dependent or receptor-independent mechanism, there was significant suppression of cholesterol synthesis and an increase in cholesteryl esters. Thus, in any situation in which receptor-dependent LDL degradation is lost, cholesterol balance in the whole animal and across individual organs is maintained by receptor-independent mechanisms, although when the new steady state is achieved, circulating levels of LDL must necessarily be very much increased.

Animals↗
PubMed1985

Rates of low density lipoprotein uptake and cholesterol synthesis are regulated independently in the liver.

The relationship between rates of hepatic sterol synthesis and rates of hepatic low density lipoprotein (LDL) uptake (clearance) was studied in animals with high (rats), low (female hamsters), and very low (male hamsters) basal rates of hepatic sterol synthesis. In rats and female hamsters, rates of hepatic sterol synthesis were varied over a 110-fold range by feeding cholesterol or cholestyramine; nevertheless, rates of hepatic LDL clearance remained essentially unchanged as did plasma LDL-cholesterol concentrations. In contrast, in male hamsters, which have a very limited capacity to synthesize cholesterol in the liver, cholestyramine feeding increased rates of hepatic LDL uptake by 2.5-fold and this was associated with a 50% reduction in plasma LDL-cholesterol concentrations. The observed increase in LDL uptake was due to an increase in receptor-dependent LDL transport while receptor-independent lipoprotein uptake remained constant. These studies suggest that rates of hepatic cholesterol synthesis and receptor-dependent LDL uptake are regulated independently. Furthermore, the primary response of the liver to changes in cholesterol availability is regulation of sterol synthesis and only when the capacity of this compensatory mechanism is exceeded is the rate of LDL transport altered.

Animals↗
PubMed1984

Measurement of rates of cholesterol synthesis using tritiated water.

Rates of sterol synthesis in various tissues commonly are assessed by assaying levels of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase on isolated microsomes or by measuring the rates of incorporation of various 14C-labeled substrates or [3H]water into cholesterol by whole cell preparations in vitro or by the tissues of the whole animal in vivo. While measurement of activities of HMG-CoA reductase or rates of incorporation of 14C-labeled substrates into cholesterol give useful relative rates of sterol production, neither method yields absolute rates of cholesterol synthesis. The use of [3H]water circumvents the problem of variable and unknown dilution of the specific activity of the precursor pool encountered when 14C-labeled substrates are used and does yield absolute rates of cholesterol synthesis provided that the 3H/C incorporation ratio is known for a particular tissue. In 12 different experimental situations it has been found that from 21 to 27 micrograms atoms of 3H are incorporated into cholesterol from [3H]water in different tissues of several animal species, so that the 3H/C incorporation ratio is similar under nearly all experimental conditions and varies from 0.78 to 1.00. When administered in vivo, [3H]water rapidly equilibrates with intracellular water and is incorporated into sterols within the various organs at rates that are linear with respect to time. From such data it is possible to obtain absolute rates of cholesterol synthesis in the whole animal and in the various organs of the animal. Current data suggest, therefore, that use of [3H]water yields the most accurate rates of cholesterol synthesis both in vitro and in vivo.

Animals↗
PubMed1984

Regulation of low density lipoprotein uptake and degradation in different animals species.

These various observations suggest that the intestinal-hepatic axis plays a key role in the regulation of cholesterol balance in the whole animal and the circulating levels of LDL-cholesterol. Nearly all sterol which enters or leaves the body must do so through the intestine and liver. Changes in the rate of entry or exit of cholesterol (or bile acids) from the animal are met by appropriate reciprocal changes in the rates of cholesterol synthesis in these two organs. As long as these adaptive changes in synthesis are adequate to meet the changing needs for cholesterol in the animal, the rates of receptor-mediated LDL degradation by the liver and intestine remain essentially unchanged as does the plasma LDL-cholesterol concentration. Only when the changes in cholesterol synthesis are inadequate to meet the changing sterol needs (or are blocked by drug administration (22] does the liver increase its rate of receptor-mediated LDL uptake which, in turn, results in significant alterations in circulating plasma LDL-cholesterol levels.

Animals↗
PubMed1983

Dissociation of hepatic cholesterol synthesis from hepatic low-density lipoprotein uptake and biliary cholesterol saturation in female and male hamsters of different ages.

These studies were carried out in order to examine the relationship between the rate of uptake of low-density lipoproteins (LDL) by the liver and the rates of hepatic and extrahepatic cholesterol synthesis and biliary cholesterol content. Female hamsters fed a regular chow diet manifested a rate of hepatic sterol synthesis that was several-fold higher than that in age-matched males maintained on the same diet. Synthesis in the small intestine did not show a corresponding sex difference, but the overall rate in the remaining tissues of the carcass was significantly lower in the females than in the males. Thus, although the proportion of newly synthesized sterol produced by the liver was substantially greater in the females, this was balanced by a smaller contribution from the extrahepatic compartment so that whole-body sterol synthesis was similar in the females and males. Sterol synthesis in the whole animal declined markedly with age in both the females and males, and this was due principally to a reduction in extrahepatic synthesis. Despite the higher rate of hepatic synthesis in females, the rate of uptake of [14C]sucrose-labeled, homologous LDL by the liver was similar in females and males. In males, the adrenal gland transported the labeled LDL at a much higher rate than in females, but in the other extrahepatic tissues the rate of LDL uptake was similar in both groups. The level of cholesterol carried in the various plasma lipoprotein fractions and the relative cholesterol content of gallbladder bile were also similar in females and males. Thus, in this experimental model, the rate of LDL transport by the liver and extrahepatic tissues, the amount of cholesterol carried in plasma lipoproteins and the degree of biliary cholesterol saturation were not directly related to the rates of endogenous hepatic and extrahepatic sterol synthesis.

Aging↗
PubMed1983

Rates of receptor-dependent and -independent low density lipoprotein uptake in the hamster.

By using a constant infusion technique in the hamster, rates of uptake of [14C]sucrose-labeled hamster low density lipoprotein (hamLDL) and methylated hamster LDL (MehamLDL) were directly measured in 15 tissues. From these measurements the magnitude of LDL receptor-dependent and receptor-independent lipoprotein transport was calculated. The whole-animal clearance of hamLDL equaled 547 microliters/hr per 100 g of body weight. LDL clearance per g of tissue was highest in the liver (114 microliters/hr per g), ovary (43), spleen (36), adrenal gland (29), and intestine (24) and was lowest in fat (0.75), brain (0.35), and muscle (0.26). When adjusted for organ weight, the sum of the absolute clearance rates in all of the tissues examined equaled the rate of whole-animal LDL turnover. Liver accounted for 73%, and the jejunum and ileum combined accounted for 7% of whole-animal clearance. The 12 other tissues each accounted for only a minor portion of LDL clearance. Rates of uptake of Me-hamLDL were much less in many tissues and accounted for only 6-12% of the uptake of LDL in the liver, ovary, adrenal gland, lung, and kidney. However, this receptor-independent uptake was quantitatively more important in the intestine (44%) and spleen (72%) and accounted for essentially all LDL uptake in organs such as muscle, skin, and brain. Thus, in the hamster, most LDL is taken up and degraded by the liver. This uptake process is greater than 90% mediated by the LDL receptor and manifests saturation kinetics. Finally, cholestyramine feeding increases receptor-mediated LDL transport in the liver but in no other tissue studied.

Adrenal Glands↗