Relationship between embryonic and tumor lipids: I. Changes in the neutral lipids of the developing chick brain,heart and liver

Organ dry weight, per cent total lipid, per cent neutral lipid, per cent phospholipid, and neutral lipid class composition of embryonic and mature brain, heart and liver were determined at 10, 13, 16, 19, 22, 27 and 53 days after incubation was initiated. All three tissues showed an increase in total lipids from the 10th day to hatching (21st day). The 10th day brain showed relatively high levels of sterol esters which decreased with increased development while free sterol levels increased. Heart free sterol and sterol ester percentages decreased with increassed time, while triglyceride levels increased dramatically after the 16th day. Liver showed a massive accumulation of neutral lipid after the 17th day. The neutral lipid was not triglyceride, as might have been expected, but sterol ester. Liver sterol, sterol ester and triglyceride levels were approximately equal at the 10th and 13th days, after which time sterol ester rose rapidly to more than 90% of the total neutral lipids by the 19th day. The neutral lipid class distributions were characteristically different for each tissue throughout embryonic development. The relative high sterol ester levels in each of the tissues early in development suggests that the high level of sterol esters in neoplastic tissue may be related to the growth process of increasing cell numbers. On the other hand, the absence or the presence of only trace amounts of glyceryl ether diesters in any of the embryonic tissues suggests that the elevated levels of this lipid class in most tumors may be related to the neoplastic process or to conditions resulting from neoplasia.     

Effect of hepatoma on host liver,heart and lung lipids as tumor growth progresses

A large group of rats was transplanted with hepatoma 7288CTC and 4 animals were sacrificed at 3-day intervals for four weeks. Lipid class concentrations, fatty acid class compositions, and the distribution ofcis octadecenoate positional isomers in the major lipid classes were determined for heart, liver and lung at each time period. The hearts of host animals decreased in dry weight as hepatoma growth progressed. At day 30, heart weights were less than two-thirds of initial weights. Lipid class concentrations changed in all three tissues: cholesterol and free fatty acids increased in liver; triglycerides and cholesterol decreased and then increased in heart; and cholesterol, triglycerides and PC decreased in lung as tumor growth progressed. Hexadecenoate percentages exhibited a progressive decrease in all the lipid classes of heart and liver. Although total octadecenoate percentages showed only minor changes, oleate concentrations generally increased and vaccenate levels decreased in heart and liver lipids as tumor growth progressed. Palmitoleate, precursor of vaccenate, exhibited decreased concentrations early that resulted in decreased vaccenate levels. Decreased palmitoleate concentrations suggest inhibition of the Δ9 desaturase system, but normal oleate concentrations complicate this interpretation. Most of the changes in the lipids were detectable 3–6 days after transplantation, indicating the hepatoma affects the lipid metabolism of the host animal early and well in advance of nutritional stresses.     

Lipids of cultured hepatoma cells: II. Effect of media lipids on cellular phospholipids

Minimal deviation hepatoma cells were cultured in a modified Swim's 77 medium supplemented with decreasing amounts of serum, lipid-free serum, and lipid-free serum containing added palmitic or linoleic acids. Cellular phospholipids were extracted and the class distribution determined quantitatively. The fatty acid composition of each phospholipid class was determined, and the percentages from cells grown on each of the various media were compared. Cellular phospholipid class and fatty acid compositions differed from media compositions, indicating that intact serum phospholipids are not incorporated into cellular structures. Phosphatidylcholine percentages decreased as the media serum and lipid levels decreased, while phosphatidylinositol and phosphatidylethanolamine percentages increased. Sphingomyelin of cells grown in medium containing added linoleic acids contained a high level of a 24∶2 acid. All classes, except sphingomyelin, contained elevated levels of 18∶1 acid and decreased levels of polyunsaturated fatty acids, relative to normal rat liver. Cells cultured on lipid-free medium did not contain increased concentrations of 20∶3 acid, suggesting that this hepatoma cell cannot desaturate monoenoic acids. Phosphoglycerides of cells, grown on lipid-free medium, had the highest monoene fatty acid concentration, whereas those cells grown on media containing added linoleic acid had the lowest concentrations, suggesting that linoleate may inhibit or regulate monoenoic acid biosynthesis in this cell. These mass data also demonstrate that monoenoic fatty acid biosynthesis in this cultured hepatoma cell responds to dietary changes.     

Role of membrane lipids in the immunological killing of tumor cells: II. Effector cell lipids

Peritoneal macrophages (MØ) from mice become cytotoxic after incubation in lymphokine (LK)-rich supernatants of antigen-stimulated spleen cell cultures. Tumoricidal activity is evident with MØ treated with LK for 4 hr, becomes maximal after 8–12 hr incubation and decreases to control levels by 24–36 hr. To gain insight into LK-induced functional changes, the lipid composition of MØ cultured with LK for 0–36 hr was analyzed by high pressure liquid chromatography. LK induced marked changes in MØ lipid composition: cellular content of cholesterol (CHOL) and polyunsaturated fatty acids increased 2- to 3-fold after 8 hr when the cells showed maximal tumoricidal activity. Cellular lipid and fatty acid content returned to control levels by 24 hr when the MØ had lost tumoricidal activity. These changes were not observed with equal numbers of MØ cultured in control supernatants. To analyze further the role of CHOL and unsaturated fatty acids in MØ tumor cytotoxicity, MØ were enriched in CHOL or linolenic acid (18∶3) and tested for their ability to kill 1023 tumor cells. Within 1 hr of culture, MØ showed a 3- to 4-fold increase in CHOL or 18∶3 content. 18∶3-enriched cells were markedly tumoricidal, whereas controls cultured in delipidized medium alone or enriched with saturated fatty acid were not cytotoxic. CHOL-enriched MØ were not tumoricidal; indeed, these cells were inhibited in their killing after treatment with LK compared to MØ cultured in delipidized medium with LK alone. These results suggest that UFA aids, whereas CHOL negates, expression of MØ tumor cytotoxicity.     

Metabolism of 1-14C linolenic acid in developing brain: II. Incorporation of radioactivity from 1-14C linolenate into brain lipids

Metabolism of 1-¹⁴C linolenic acid was studied in growing animals by injecting the tracer intraperitoneally into 12–13 day old suckling rats and following up the results by sacrificing groups of animals at 8 hr, 48 hr, 15 day, and 45 day intervals. In the first 15 days, there was a greater decrease in radioactivity of brain total lipids compared to the later period, although the earlier age period is characterized by lipid deposition rather than breakdown. Since the 18∶3 ω3 family of fatty acids occurs largely in the brain total phosphatidyl ethanolamine fraction, we expected that, in the initial period, total phosphatidyl ethanolamine would be the most highly radioactive component. However, results showed that 8 hr after the tracer phosphatidyl choline had the highest specific radioactivity. When the total phosphatidyl ethanolamine fraction was resolved into diacyl and alk-1-enyl species, it was found that radioactivity was not distributed evenly between the two species. There was a progressive increase in radioactivity of the alkenyl and a decrease in the diacyl species. Forty-eight hr after the tracer, however, the radioactivity of phosphatidyl ethanolamine increased and at 45 days remained slightly higher than phosphatidyl choline. Radioactivity of cholesterol, a result of synthesis from acetate undoubtedly derived from the breakdown of tracer linolenate, was also high 48 hr after tracer and remained high until 45 days.     

Fatty acid composition of phospholipids in different regions of developing human fetal brain

The fatty acid composition of total phospholipids in different regions, viz., cerebrum, cerebellum and medulla oblongata, of developing human fetal brain was studied. All the brains analyzed in the present investigations were obtained from fetuses whose mothers belonged to the poor socioeconomic section of the population. Palmitic, oleic and stearic acids were found to be the dominant fatty acids, and the pattern was similar in all regions of the brain studied between the ages of 22 and 35 weeks. However at birth there appeared to be an increase in polyenoic acids at the expense of lower chain fatty acids, and these changes were of relatively higher magnitude in the cerebellum than in other regions studied. These changes, in terms of increase in polyunsaturated fatty acids near full term, coincided well with the already observed timing of an overall growth spurt of the brain a few weeks preceding birth.     

Rapid and convenient separation of phospholipids and non phosphorus lipids from rat heart using silica cartridges

The separation of non phosphorus lipids and phospholipids of rat heart using Sep-pack Silica cartridges is described. No cartridge preparation is necessary before utilization. The separation of lipid extracts is very fast. A complete partition of non phosphorus lipids and phospholipid is obtained.     

Ketone bodies serve as important precursors of brain lipids in the developing rat

Ketone bodies are readily oxidized for energy by extrahepatic tissues. Since oxidation of ketone bodies produces acetyl coenzyme A (AcCoA), and hence could be an important source of immediate precursors for fatty acid synthesis, we investigated, in whole-brain homogenates of developing rats, the preferential utilization of [3-¹⁴C]acetoacetate (AcAc), [3-¹⁴C]β-hydroxybutyrate (β-OHB), and [U-¹⁴C]glucose for production of CO₂ and lipids, including phospholipids, glycerides, cholesterol, and free fatty acids. Throughout the postnatal period, the rate of AcAc oxidation was 2–3 and 2–6 times the rate for β-OHB and glucose, respectively. The eynthesis of lipids from AcAc was 7- to 11-fold higher than from glucose. The brain’s capacity for lipid synthesis from β-OHB was similar to that from AcAc during the first 8 days of life; however, during the next 10 days, the synthesis of lipids from β-OHB decreased to 60% of AcAc-dependent synthesis. The high rate of lipid synthesis from ketone bodies was accompanied by increased activities of cytoplasmic acetoacetyl CoA synthetase and acetoacetyl CoA thiolase in the developing brain. During the entire postnatal development, the proportion of radioactivity claimed by lipids vs. CO₂ from [3-¹⁴C]AcAc was 44–62% vs. 38–56%; from [3-¹⁴C]β-OHB, 50–81% vs. 19–50%; and from [U-¹⁴C]glucose, 14–43% vs. 57–86%. Phospholipids accounted for more than two-thirds of total lipids synthesized from either ketone bodies or glucose, while diglycerides plus cholesterol and free fatty acids accounted for most of the remainder. Addition of glucose to the incubation medium did not alter lipid production from AcAc throughout the suckling period, but moderately depressed energy production in the brain of 16- to 20-day-old rats. It is clear that in cell-free preparations from the brain of developing rats, ketone bodies are preferred over glucose as precursors for both energy and lipids, mainly phospholipids. These results suggest that ketone bodies are important for the growth and development of the brain.     

Early dietary intervention with structured triacylglycerols containing docosahexaenoic acid. Effect on brain, liver, and adipose tissue lipids

Newborn rats were fed liquid diets containing 7 wt% fat in which 3.8% of the total fatty acids were 22:6n-3. The fats were either a specific structured oil with 22:6n-3 mostly located in the sn-2 position or a randomized oil with 22:6n-3 equally distributed in the triacylglycerol (TAG) molecules. The oils were manufactured by interesterification of fish oil TAG with free fatty acids from butterfat. The pups were tube-fed three times a day and stayed with their dams during the night. After 14 d they were fed solid diets containing the same oils for the next 7 d. A reference group stayed with the dams and received ordinary rat chow at weaning. In general no significant differences between the two dietary treatments were observed in the tissues examined except for adipose tissue. The levels of 22:6n-3 were significantly increased in brain phosphatidylcholines (PC) and phosphatidylserines (PS) of both experimental groups compared with the reference group after three weeks, whereas no differences were found in brain phosphatidylethanolamines (PE) and phosphatidylinositols (PI). In all groups and all phospholipids examined, the levels of 20:4n-6 generally decreased from 1 to 3 wk and were significantly lower in the experimental groups compared with the reference group at 3 wk except for PI. In liver, PC and PE 22:6n-3 remained constant in the experimental groups but decreased significantly in the reference group, whereas in liver PS 22:6n-3 increased in all groups, but reached significantly higher levels in the experimental groups than in the reference group. In adipose tissue, 22:6n-3 increased in the experimental groups during the study period, but decreased in the reference group, suggesting that a surplus of dietary 22:6n-3 was stored.     

Changes in liver lipids after administration of 2-decanoylamino-3-morpholinopropiophenone and chlorpromazine

The enzyme which forms glucocerebroside, ceramide: UDP-glucose glucosyltransferase, is inactivated in vitro by a cationic analog of cerebroside, 2-decanoylamino-3-morpholinopropiophenone. A study of the inhibitor using intraperitoneal injection into young mice showed that the level of the enzyme activity in liver was appreciably lowered between 3 and 6 hr after injection. The activity increased subsequently, overshooting the normal level within 24 hr by about 20%, then returning to normal within the next 24 hr. Additional effects observed in liver were an increase in lipid content (primarily in the triglyceride fraction and ceramides) and a decrease in the glucocerebroside level. Body temperature dropped rapidly. Markedly similar effects were produced by injecting chlorpromazine, which was tried in order to reduce the hyperirritability and inhibitory effects on monoamine oxidase previously demonstrated by the glucosyltransferase inhibitor. Chlorpromazine did indeed block the hyperirritability and resulted in enhancement of the keto amine's effects on the enzyme and lipids. It is possible that the two drugs in combination would be helpful in ameliorating the symptoms due to the cerebroside accumulation that occurs in Gaucher disease. Diazepam also produced a reduced level of glucosyltransferase. A color reaction for chlorpromazine, possibly suitable for quantitative determination in tissues, was accidentally discovered.     

Studies on the lipids of sheep red blood cells. II. The incorporation of phosphorus into phospholipids of HK and LK cells

The incorporation of inorganic phosphate (as NaH₂PO₄) into the phospholipids of sheep red blood cells was studied in vitro in blood samples from five highpotassium (HK) and five low-potassium (LK) sheep. The erythrocytes from HK sheep incorporated more activity in 4 hr than those from the LK sheep. However no activity was incorporated into the major phospholipids of the cells (phosphatidyl ethanolamine, phosphatidyl serine, and sphingomyelin) of either group. The phosphatidic acid fraction was labeled in both groups and to a significantly greater extent in the HK samples. However the highest activity in the phospholipid of sheep red-cells was located in three unknown compounds not previously detected. Their specific activities were the same in the HK and the LK samples although they were present in slightly larger amounts in the HK samples. In general, incorporation was at a rather low level, and from stoichiometric considerations it was concluded that the metabolism in the red-cell phospholipids could not be directly involved in the active transport of ions across the cell membrane. This work also confirmed a previous report that no quantitative differences exist among the major phospholipid classes in the two types of cells.     

Role of membrane lipids in the immunological killing of tumor cells: I. Target cell lipids

The metabolic and physical properties of tumor cells that are associated with their ability to resist or escape from immune attack have been investigated. The susceptibility of P815 murine-mastocytoma cells to immune killing can be modulated. Culturing the cells with adriamicin or with hydrocortisone increases or decreases, respectively, the sensitivity of the cells to killing by antibody (Ab) plus complement (C); in addition, culturing the cells with mitomycin C or hydrocortisone increases or decreases, respectively, the sensitivity of the cells to killing by cytotoxic T lymphocytes (CTL). The susceptibility of the cells to Ab-C killing correlates with the ability of the cells to synthesize complex cellular lipids, but not DNA, RNA, protein, or carbohydrate. Further, tumor cells rendered sensitive to Ab-C killing by adriamycin are decreased in total lipid content and in their cholesterol/phospholipid mole ratio; hydrocortisone-treated resistant cells showed the opposite effects. The ability of tumor cells to resist CTL killing did not correlate with their total cellular lipid synthesis, but did correlate with the synthesis and composition of specific cellular phospholipids. In addition, tumor cells increased in sensitivity to Ab-C killing exhibited an increase in cell surface membrane fluidity, whereas cells increased in suceptibility to CTL attack showed an increase in their net negative cell surface charge density. These data show certain unique chemical and physical properties of tumor cells to be of fundamental importance for their ability to resist either humoral or cell-mediated immunologic attack; modulation of one or another of these cellular properties results in a change in the cells' susceptibility to immune killing by antibody plus C or by cytotoxic T lymphocytes. Presented at the 73rd Annual Meeting of the American Oil Chemists' Society in Toronto, Canada, May 1982.     

Studies on the role of phospholipids in the triglyceride cycle: II. Turnover of plasma phospholipids in ethionine-treated dogs

The disappearance of native labeled plasma phospholipids (nPLP³²) was abruptly halted in the plasma of normal mongrel dogs shortly after givingdl-ethionine by intraperitoneal injection. In other dogs, chronic feeding of ethionine over a period of three days prior to these measurements prolonged the turnover time of plasma phospholipids. This impairment in the turnover of plasma PL brought about by ethionine administration occurs regardless of sex differences in lipid metabolism or other physiological differences relating to the nutritional status of the animal. The amount of nPLP³² found in the liver at the end of the turnover experiments was also measured. These data suggest that phospholipid transport from plasma to liver is not impaired by ethionine. The possible significance of an ethionine-induced choline deficiency which impairs transport of triglycerides and phospholipids from the liver to plasma is considered in regard to the role of phospholipids in the triglyceride cycle. Presented in part at the 58th Annual AOCS Meeting, New Orleans 1967.     

Changes of fatty acid composition of phospholipids in liver mitochondria and microsomes of the rat during growth

The fatty acid patterns of rat liver mitochondrial and microsomal phospholipids were analyzed from term fetuses, 1 and 4 days old, and adult rats. The main fatty acids of phosphatidylethanolamine and-choline were stearic and palmitic acids, although the patterns differed slightly. The fatty acid composition of corresponding phospholipids in mitochondria and microsomes was similar. The fatty acid pattern of cardiolipin was dominated by linoleic acid. The most consistent feature of the developmental changes in the fatty acid patterns of all phospholipids studied was a decrease in the relative amount of monounsaturated fatty acids. The percentages of saturated fatty acids in phosphatidyl-ethanolamine and-choline increased during neonatal development. It is suggested that the high levels of fetal monounsaturated fatty acids were due to low availability of polyunsaturated fatty acids.     

Fatty acid composition of milk phospholipids. II. Sheep,Indian buffalo and human milks

Phospholipids were isolated from sheep, Indian buffalo, and human milks, and their fatty acid compositions determined by gas chromatography. The specific distributions of fatty acids in phosphatidyl cholines (PC) and phosphatidyl ethanolamines (PE) were determined after phospholipase A hydrolysis. Fatty acid compositions and specific distributions were similar in sheep and buffalo milk phospholipids, and compared closely with those of bovine milk. Human milk phospholipids, particularly PE, contained much larger amounts of polyunsaturated acids, but negligible amounts of branchedchain acids. Palmitic and oleic acids were evenly distributed in human milk PC and PE, whereas they were preferentially located in the α′ position in PC and PE of ruminant milks. The results are discussed in the context of current theories of lipid biosynthesis. Part I of this series is “Fatty Acids of Bovine Milk Glycolipids and Phospholipids, and Their Specific Distribution in the Diacylglycerophospholipids,” W. R. Morrison, E. L. Jack and L. M. Smith. JAOCS,42, 1142–1147 (1965).     

Changes in lipids in liver and serum of rats fed a histidine-excess diet or cholesterol-supplemented diets

The influence of dietary excess (5%) L-histidine on serum and liver lipids was examined in rats. Feeding a histidine-excess diet for 3, 6, 14 or 30 days caused growth retardation, hepatomegaly and decreased liver lipids throughout the period of the experiment. Hypercholesterolemia was observed after feeding a histidine-excess diet for 6 days; then serum cholesterol continuously increased for 30 days. Serum triglyceride on day 30 in rats fed the histidine-excess diet showed a significant decrease compared to rats fed the basal diet. Serum phospholipids of rats fed the histidine-excess diet for 7 or 14 days showed a significant increase compared to rats fed the basal diet. When rats were fed a basal, histidine-excess or cholesterol-supplemented diet (0.5% and 1.0% cholesterol) for 6 days, the distribution of serum high density (HDL), low density (LDL) and very low density lipoprotein cholesterol in rats fed the histidine-excess diet was similar to that of rats fed the basal diet, whereas LDL-cholesterol increased and HDL-cholesterol decreased in rats fed the cholesterol-supplemented diet.     

Changes in fatty acid composition of phospholipids from liver microsomes and nuclei in rats fed a choline-free diet

Male F-344 rats were fed a choline-free (CF) diet, and changes in phospholipid content, phospholipid fatty acids and phospholipase A₂ activity in liver nuclei and microsomes were examined during the first 72 hr. Both nuclei and microsomes showed a decrease in phosphatidylcholine (PC) content. Microsomes showed an increase in PC arachidonate while nuclei showed a decrease. Also, microsomes showed increased activity of phospholipase A₂ (PLA₂) while nuclei did not. These observations are consistent with the hypothesis that the absence of diene conjugates in liver microsomes in the rats on the CF diet may reflect the increased rate of removal of peroxidized fatty acids by phospholipase A₂.     

Ether-containing lipids of the slime mold,Physarum polycephalum: II. Rates of biosynthesis

The in vivo incorporation of 1-¹⁴C-palmitic acid and 1-0-[8,9-³H] hexadecyl glycerol (chimyl alcohol) by plasmodia of the slime mold,Physarum polycephalum has been studied.¹⁴C-palmitate rapidly enters ester and alkyl ether side chains of phospholipids, but alk-1-enyl side chains are labeled more slowly.³H-chimyl alcohol is incorporated into the alkyl ether phospholipids, which appear to undergo enzymatic desaturation, producing plasmalogens. The feasibility ofPhysarum as the source of a cell-free enzyme system for plasmalogen synthesis is discussed.     

Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat

The incorporation of radioactivity from orally administered linoleic acid-1-¹⁴C, linolenic acid-1-¹⁴C, arachidonic acid-³Hg, and docosahexaenoic acid-¹⁴C into the liver and brain lipids of suckling rats was studied. In both tissues, 22 hr after dosing, 2 distinct levels of incorporation were observed: a low uptake (from 18∶2-1-¹⁴C and 18∶3-1-¹⁴C) and a high uptake (from 20∶4-³H₈ and 22∶6-¹⁴C). In adult rats, the incorporation of radioactivity into brain lipids from 18∶2-1-¹⁴C and 20∶4-³H was considerably lower than the incorporation into the brains of the young rats. In the livers of the suckling rats, the activity from the 18 carbon acids was associated mostly with the triglyceride fraction, whereas the activity from the 20∶4-³H₈ and 22∶6-¹⁴C was concentrated in the phospholipid fraction. In the brain lipids, the activity from the different fatty acids was associated predominantly with the phospholipids. In the liver and brain phospholipid fatty acids, some of the activity in the 18∶2-1-¹⁴C and 18∶3-1-¹⁴C experiments was associated with 20 and 22 carbon polyunsaturated fatty acids; however, radioactivity from orally administered 20∶4-³H₈ and 22∶6-¹⁴C was incorporated intact into the tissue phospholipid to a much greater extent compared with the incorporation of radioactivity into 20∶4 and 22∶6 in the experiments where 18∶2-1-¹⁴C and 18∶3-1-¹⁴C, respectively, were administered. Possible reasons for these differences are discussed. Rat milk contains a wide spectrum of polyunsaturated fatty acids, including linoleate, linolenate, arachidonate, and docosahexaenoate. During the suckling period in the rat, there is a rapid deposition of 20∶4 and 22∶6 in the brain. The results of the present experiments suggested that dietary 20∶4 and 22∶6 were important sources of brain 20∶4 and 22∶6 in the developing rat.     

Relative utilization of fatty acids for synthesis of ketone bodies and complex lipids in the liver of developing rats

The regulation of hepatic ketogenesis, as related to the metabolism of fatty acids through oxidative and synthetic pathways, was studied in developing rats. [1-¹⁴C] palmitate was used as a substrate to determine the proportions of free fatty acids utilized for the production of ketone bodies, CO₂ and complex lipids. Similar developmental patterns of hepatic ketogenesis were obtained by measuring the production of either [¹⁴C]acetoacetate from exogenous [1-¹⁴C] palmitate or the sum of unlabeled acetoacetate and β-hydroxybutyrate from endogenous fatty acids. The production of total ketone bodies was low during the late fetal stage and at birth, but increased rapidly to a maximum value within 24 hr after birth. The maximal ketogenic capacity appeared to be maintained for the first 10 days of life.¹⁴CO₂ production from [1-¹⁴C] palmitate increased by two- to fourfold during the suckling period, from its initial low rate seen at birth. The capacity for synthesis of total complex lipids was low at birth and had increased by day 3 to a maximal value, which was comparable to that of adult fed rats. The high lipogenic capacity lasted throughout the remaining suckling period. When ketogenesis was inhibited by 4-pentenoic acid, the rate of synthesis of complex lipids did not increase despite an increase in unutilized fatty acids. During the mid-suckling period, approximately equal amounts of [1-¹⁴C] palmitate were utilized for the synthesis of ketone plus CO₂ and for complex lipid synthesis. By contrast, in adult fed rats, the incorporation of fatty acids into complex lipids was four times higher than that of ketone plus CO₂. These observations suggest that stimulated hepatic ketogenesis in suckling rats results from the rapid oxidation of fatty acids and consequent increased production of acetyl CoA, but not from impaired capacity for synthsis of complex lipids.