Regulation Of Serum Cholesterol Research Articles

Saturated Fats: Time to Assess Their Beneficial Role in a Healthful Diet

Saturated fats are widely seen as undesirable components of a healthy diet, as a result of their illusory association with elevated serum cholesterol. The regulation of serum cholesterol is now better understood and a lack of polyunsaturated fatty acids, rather than an abundance of saturated fatty acids, is responsible. Palmitic acid was shown to incite inflammation at unnaturally high concentrations in tissue culture, but later was found to play an auxiliary role as a precursor to ceramide biosynthesis and possibly in the palmitoylation of membrane receptors involved in the initiation of inflammation. Studies of arthritic inflammation in lab animals showed that dietary saturated fats are anti-inflammatory, whereas polyunsaturated oils are pro-inflammatory. Inflammation plays a role in numerous metabolic diseases, including insulin resistance, fatty liver disease and metabolic syndrome, among others. Fat, as triglycerides in adipose tissue, is an efficient way for living organisms to store energy and reduce the toxicity of other macronutrients. Macronutrients, such as excess carbohydrates and polyunsaturated fatty acids, are converted to saturated and monounsaturated fatty acids for storage as triglycerides in adipose tissue. Fatty acids are released from adipose tissue during fasting and as a result of some metabolic disorders, where elevated levels of nonesterified fatty acids in blood can lead to hepatic lipid accumulation, inflammation and insulin resistance. Although most serum nonesterified fatty acids may be saturated fatty acids, they are not necessarily derived from the diet. This paper will attempt to clarify the role of saturated fatty acids, and palmitic acid in particular, with regard to certain adverse health conditions.

Coconut milk gavage enhanced fecal bile excretion by modulating hepatic Fxr expression but failed to improve fasting serum cholesterol profile in C57BL/6 mice

The consumption of coconut milk has long been regarded as detrimental to cardiovascular health due to its high saturated fatty acid content. Contradictorily, emerging evidences have highlighted that the fatty acids in coconut lipids, which comprise mostly of medium-chain fatty acids (MCFA), may be beneficial to the regulation of serum cholesterol. To identify the potential health effect of coconut milk on lipid metabolism, this current study employed an intragastric gavage method on C57BL/6 mice to investigate the physiological and molecular alteration in the mice subject after 8 weeks of gavage intervention. The supplementation of coconut milk did not affect the levels of serum triglyceride, but it induced the total serum cholesterol after 2 weeks of treatment. The serum cholesterol level subsequently plateaued, but an increase in bile acid excretion was observed, most likely through the modulation of bile regulating genes, i.e. farnesoid X receptor (Fxr) and Cyp7a1. Despite that, the total cholesterol to HDL cholesterol ratio of coconut milk group was comparable to that of the light cream group. In short, coconut milk supplementation promoted cholesterol excretion through the fecal bile route but did not significantly improve the serum cholesterol profile of C57BL/6 mice.

The bioinformatics aspects of gene screening of HT-29, human colon cell line treated with caffeic acid.

To better understand the anticancer properties of coffee, bioinformatics analysis of gene expression profile of HT-29, human colon cell line in the exposure of caffeic acid (CA) is proposed in this study. Coffee as a popular beverage has been shown to be a potential health promoter as well as being effective on different kinds of diseases including cancer. The differentially expressed genes (DEGs) across the comparison of groups of samples including none-treated HT-29 and HT-29 tread with CA were applied for the protein-protein interaction mapping. Cytoscape v.3.7.1 constructed a network and analyzed the topological features of the most noteworthy DEGs. The genes of CTSZ, AFF4, DHRS2, and HMGCS1 known as active agents in cancer progression, were identified as the central DEGs in the constructed PPI network in this study. Especially, HMGCS1 is the most central gene is also linked to one of the important colon cancer altered processes, cholesterol metabolism. Lowering the risk of colon cancer could be perhaps through nominated DEGs and therefore, regulation of serum cholesterol as well as protection against cancer development.

The perspective on cholesterol-lowering mechanisms of probiotics.

The use of probiotics as food components combats not only cardiovascular diseases but also many gastrointestinal tract disorders. Their health benefits along with their increased global market have interested scientists for better formulation and appropriate administration to the consumers. However, the lack of clear elucidation of their cholesterol-lowering mechanisms has complicated their proper dosage and administration to the beneficiaries. In this review, proposed mechanisms of cholesterol reduction such as deconjugation of bile via bile salt hydrolase activity, binding of cholesterol to probiotic cellular surface and incorporation into their cell membrane, production of SCFAs from oligosaccharides, coprecipitation of cholesterol with deconjugated bile, and cholesterol conversion to coprostanol have been discussed. Also, hypocholesterolemic effects on human- and animal-trial results, commonly used probiotics and synbiotics with effect on serum cholesterol regulation, types of bile salt hydrolase genes, and substrate specificities have been discussed.

Yacon (Smallanthus sonchifolius): A Functional Food

Yacon (Smallanthus sonchifolius) is an Andean tuberous root that is regarded as a functional food given that it contains fructooligosaccharides (FOS), inulin and phenolic compounds. The consumption of FOS and inulin improves the growth of bifidobacteria in the colon, enhances mineral absorption and gastrointestinal metabolism and plays a role in the regulation of serum cholesterol. Furthermore, the literature reports that the consumption of these prebiotics promotes a positive modulation of the immune system, improving resistance to infections and allergic reactions. Certain studies have demonstrated the potential of yacon as an alternative food source for those patients with conditions that require dietary changes. This review intends to describe the potential of yacon as a prebiotic and its cultivation and industrial processing for human consumption.

Supplementation of Either Conjugated Linoleic Acid or γ-linolenic Acid with or without Carnitine to Pig Diet Affect Flavor of Pork and Neutrophil Phagocytosis

In this study, four different oils containing either CLA, GLA, GLA+Carnitine or corn oil (control) were supplemented to finishing pigs (average 70.8 kg initial BW) diet for 28 d of feeding period. To evaluate the values of the dietary fatty acids, especially in view of sensory and nutritional characteristics of pork; pig performances, carcass characteristics, serum cholesterol, neutrophil phagocytosis, TBARS, electronic nose flavor and fatty acids profile of pork were measured. There were no differences in daily gain and nutrients digestion among treatments, but daily feed intake of CLA enriched diet was lower (P<0.05) than that of other diets. There were no differences in backfat thickness, dressing percentage and carcass grade among pigs fed diets supplemented with different oils. Serum total cholesterol showed a tendency to be lowered in pigs fed GLA enriched diet. TBARS values during storage of pork were higher in belly from pigs fed control diet whereas the values of belly from pigs fed GLA+Carnitine diet were lower than others. However, difference in TBARS was not remarkable in adipose tissue and 4 weeks extended storage regardless of pork parts. Proportion of saturated fatty acids such as C16:0 and C18:0 were higher (P<0.05) in pork loin and thin skirt from pigs fed CLA enriched diet compared to those from other diets. There were no differences in fatty acids profiles of belly and adipose tissue. CLA accumulation in pork was increased by the dietary CLA supplementation and this could be also confirmed by a slight de novo synthesis of CLA in pork from pigs fed CLA free diets. GLA was selectively accumulated to pork adipose tissue and loin from pigs fed GLA enriched diets. There was no accumulation of GLA when GLA was not supplemented, indicating no de novo synthesis of GLA. Phagocytic activity was the highest (p<0.05) in neutrophil of pigs fed GLA+Carnitine supplemented diet, then, followed by pigs fed GLA supplemented diet. There was no difference in phagocytosis between control and CLA treatment although the phagocytosis was numerically lowest in pig fed CLA enriched diet. There were distinct differences in electronic nose flavor pattern among treatments regardless of the parts. This study showed that dietary supplementation of functional fatty acids like CLA or GLA was able to result in characteristic differences in feed intake, TBARS, fatty acids profile and flavor of pork, serum cholesterol regulation and neutrophil phagocytosis. (Key words : CLA, GLA, Carnitine, Pork quality, Fatty acids profile, Flavor, Phagocytosis)

The changing face of nutritional thought--retrospect and prospect.

DIET AND HEART DISEASE The results of an elegantly and well -carried-out clinical trial show that dietary regulation of serum cholesterol in man can indeed diminish the risk of coronary heart disease.

Phytosterols as functional food ingredients: linkages to cardiovascular disease and cancer

To examine experimental evidence that has examined association of phytosterols and the reduction of the risk of cardiovascular disease and cancer. Phytosterols exist as naturally occurring plant sterols that are present in the nonsaponifiable fraction of plant oils. Phytosterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra methyl or ethyl group; however, phytosterol absorption in humans is considerably less than that of cholesterol. In fact, phytosterols reduce cholesterol absorption, although the exact mechanism is not known, and thus reduce circulating levels of cholesterol. The efficacy of phytosterols as cholesterol-lowering agents have been shown when incorporated into fat spreads as well as other food matrices. In addition, phytosterols have been combined with other beneficial dietary components including fish and olive oils, psyllium and beta-glucan to enhance their effect on risk factors of cardiovascular disease. Phytosterols appear not only to play an important role in the regulation of cardiovascular disease but also to exhibit anticancer properties. A side effect associated with the consumption of phytosterols is that they reduce the blood levels of carotenoid. Nevertheless, it has been suggested that compensation for this impact on serum carotenoid levels can occur either by increasing the intake of carotenoid-rich foods or by taking supplements containing these carotenoids. Dietary phytosterols appear to play an important role in the regulation of serum cholesterol and to exhibit anticancer properties.

Serum cholesterol and expression of ApoAI, LXRβ and SREBP2 in vitamin D receptor knock-out mice

Vitamin D insufficiency has been reported to be associated with increased blood cholesterol concentrations. Here we used two strains of VDR knock-out (VDR-KO) mice to study whether a lack of vitamin D action has any effect on cholesterol metabolism. In 129S1 mice, both in male and female VDR-KO mice serum total cholesterol levels were significantly higher than those in wild type (WT) mice (20.7% ( P = 0.05) and 22.2% ( P = 0.03), respectively). In addition, the serum high-density lipoprotein-bound cholesterol (HDL-C) level was 22% ( P = 0.03), respectively higher in male VDR-KO mice than in WT mice. The mRNA expression levels of five cholesterol metabolism related genes in livers of 129S1 mice were studied using quantitative real-time PCR (QRT-PCR): ATP-binding cassette transporter A1 (ABCA1), regulatory element binding protein (SREBP2), apolipoprotein A-I (ApoAI), low-density lipoprotein receptor (LDLR) and liver X receptor beta (LXRβ). In the mutant male mice, the mRNA level of ApoAI and LXRβ were 49.2% ( P = 0.005) and 38.8% ( P = 0.034) higher than in the WT mice. These changes were not observed in mutant female mice, but the female mutant mice showed 52.5% ( P = 0.006) decrease of SREBP2 mRNA expression compared to WT mice. Because the mutant mice were fed with a special rescue diet, we wanted to test whether the increased cholesterol levels in mutant mice were due to the diet. Both the WT and mutant NMRI mice were given the same diet for 3 weeks before the blood sampling. No difference in cholesterol or in HDL-C between WT and mutant mice was found. The results suggest that the food, gender and genetic background have an effect on the cholesterol metabolism. Although VDR seems to regulate some of the genes involved in cholesterol metabolism, its role in the regulation of serum cholesterol seems to be minimal.

Pituitary control of cholesterol metabolism in normal and LDL receptor knock-out mice: Effects of hypophysectomy and growth hormone treatment

The pituitary is important in the control of lipid metabolism and studies of hypophysectomized (Hx) rats have shown strong effects of growth hormone (GH) on bile acid synthesis, hepatic LDL receptor (LDLR) expression and on the sensitivity to dietary cholesterol. It is unclear if mice may be used in such studies. The aim of the current study was to evaluate if Hx mice may be used to further explore how GH modulates cholesterol and bile acid metabolism, and to define the importance of the LDLR in this regulation by studying LDLR-deficient mice (LDLRko). Experiments on three mouse strains showed that, following Hx, HDL were reduced and LDL increased. Cholesterol/fat feeding of Hx mice increased serum cholesterol levels 2- to 3-fold. Serum triglycerides were reduced 50% in Hx mice; a further 30% reduction was seen after dietary cholesterol/fat. A serum marker for CYP7A1-mediated bile acid synthesis (C4) increased 2-fold in intact mice on cholesterol/fat diet. In Hx mice C4 levels were reduced by 50% as compared to intact controls, but were unexpectedly increased to levels seen in normal mice upon cholesterol/fat feeding. Hx of LDLRko mice moderately increased LDL-cholesterol and reduced triglycerides and GH treatment attenuated these effects; serum C4 levels were increased by GH treatment in all groups. In conclusion, mice can be used to explore the role of the pituitary in lipid metabolism. CYP7A1 is generally reduced in Hx mice but has a normal stimulatory response following dietary cholesterol suggesting that faulty regulation of CYP7A1 is not important for the reduced resistance to dietary cholesterol in Hx mice. Further, the LDLR is only to a minor part involved in the pituitary regulation of serum cholesterol in mice.

Isoform-dependent actions of thyroid hormone nuclear receptors: Lessons from knockin mutant mice

Thyroid hormone nuclear receptors (TRs) mediate the biological activities of the thyroid hormone (T3) in growth, development and differentiation and in the maintenance of metabolic homeostasis. They are derived from two separate genes to yield four major T3-binding isoforms: α1, β1, β2, and β3. To understand whether TR isoforms mediate specific functions in vivo, PV mutation, identified from a patient with resistance to thyroid hormone (RTH), was targeted to the TRβ (TRβPV mice) or TRα gene (TRα1PV mice). PV has a frame-shift mutation in the last 14 carboxyl-terminal amino acids of TRβ1 or TRα1, resulting in the loss of T3-binding and transcriptional activities. TRβPV mice faithfully reproduce human RTH with dysfunction of the pituitary–thyroid axis, impairment in weight gain and accelerated bone development, hearing defects, abnormal regulation of serum cholesterol and increased physical activity reminiscent of attention deficit-hyperactivity disorder. In contrast, TRα1PV mice show no abnormalities in the pituitary–thyroid axis and other discernable RTH phenotypes. In addition, TRα1PV mice are dwarfs with high mortality, reduced fertility and survival, reduced glucose utilization in the brain and marked delay in bone development. These results clearly show that the molecular actions of TRα1PV are distinct from those of TRβPV in vivo. Further studies indicate that these contrasting phenotypes are mediated by distinct isoform-dependent abnormal regulation of T3-target genes in tissues. Thus, these two mutant mice provide a valuable tool for further dissecting the molecular bases of isoform-dependent actions of mutant TRs in vivo and their roles in disease.

Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis.

Lipoprotein lipase (LPL) synthesis by macrophages is upregulated in early atherogenesis, implicating the possible involvement of LPL in plaque formation. However, it is still unclear whether macrophage-derived LPL displays a proatherosclerotic or an antiatherosclerotic role in atherosclerotic lesion development. In this study, the role of macrophage-derived LPL on lipid metabolism and atherosclerosis was assessed in vivo by transplantation of LPL-deficient (LPL-/-) and wild-type (LPL+/+) bone marrow into C57BL/6 mice. Eight weeks after bone marrow transplantation (BMT), serum cholesterol levels in LPL-/--->C57BL/6 mice were reduced by 8% compared with those in LPL+/+-->C57BL/6 mice (P:<0.05, n=16), whereas triglycerides were increased by 33% (P:<0.05, n=16). Feeding the mice a high-cholesterol diet increased serum cholesterol levels in LPL-/--->C57BL/6 and LPL+/+-->C57BL/6 mice 5-fold and 9-fold, respectively, resulting in a difference of approximately 50% (P:<0. 01) after 3 months on the diet. No effects on triglyceride levels were observed under these conditions. Furthermore, serum apolipoprotein E levels were reduced by 50% in the LPL-/--->C57BL/6 mice compared with controls under both dietary conditions. After 3 months on a high-cholesterol diet, the atherosclerotic lesion area in LPL-/--->C57BL/6 mice was reduced by 52% compared with controls. It can be concluded that macrophage-derived LPL plays a significant role in the regulation of serum cholesterol, apolipoprotein E, and atherogenesis, suggesting that specific blockade of macrophage LPL production may be beneficial for decreasing atherosclerotic lesion development.

Reproductive Phase-Dependent Annual Variation in the Effects of Melatonin and Pinealectomy, with or without Iopanoic Acid/Cyproterone Acetate, in the Regulation of Serum Cholesterol in Clarias batrachus

The present study was aimed at examining the putative thyroid or androgen dependency of the roles of melatonin/the pineal in the regulation of serum cholesterol in a freshwater catfish, Clarias batrachus. During four different phases of the annual gonadal cycle melatonin-treated or pinealectomized fishes received either iopanoic acid or cyproterone acetate or vehicle in the early morning or late afternoon. The results indicate that the effects of melatonin on serum cholesterol appear to be thyroid and testis independent during the preparatory and late postspawning phases. In contrast, the effect of pinealectomy is brought about mainly by way of the thyroid and/or the testis.

Growth hormone regulation of serum lipoproteins in the rat: Different growth hormone regulatory principles for apolipoprotein (apo) B and the sexually dimorphic apo E concentrations

Growth hormone (GH) regulation of serum lipoproteins and apolipoproteins was studied using hypophysectomized (Hx) male and female Sprague-Dawley rats. Hypophysectomies were performed at 45 or 50 days of age. Hx rats were given replacement therapy with l-thyroxine (10 μg/kg/d) and hydrocortisone (400 μg/kg/d) unless otherwise specified. Bovine GH (bGH) was given either as two daily subcutaneous (SC) injections at 12-hour intervals or as a continuous SC infusion. Serum cholesterol and apolipoprotein (apo) E concentrations decreased after Hx of female rats. In contrast, Hx of male rats resulted in increased serum cholesterol concentrations and had no effect on serum apo E concentrations. There were no effects of Hx on high-density lipoprotein (HDL) apo E levels in male rats in contrast to female rats. bGH given twice daily to Hx male rats had no effect on HDL apo E levels, but a continuous infusion of bGH resulted in a marked increase in HDL apo E concentration, to levels above those of intact male rats. As previously observed in female rats, serum and HDL apo A-I concentrations decreased and serum and low-density lipoprotein (LDL) concentrations of apo B increased after Hx of male rats. Treatment with l-thyroxine and hydrocortisone reduced the serum concentrations of apo B. bGH given alone resulted in even lower concentrations of apo B. Serum concentrations of cholesterol and apo E were unaffected by replacement therapy with l-thyroxine and hydrocortisone. Treatment with bGH alone had similar effects on serum cholesterol, apo E, and apo B concentrations as treatment with l-thyroxine, hydrocortisone, and bGH in combination. The time course and dose-response relationship for the effects of GH were studied in Hx female rats. Serum apo B concentrations increased during the first day after Hx and decreased after 1 day of bGH treatment. The changes in apo E concentration were observed 3 days after Hx and 3 to 7 days after initiation of hormonal treatment, respectively. The apo B concentration decreased dose-dependently and reached the levels of intact females when the highest doses (1 to 2 mg/kg/d) of bGH were given. In contrast, the apo E concentration increased to the levels of intact females when a low dose (0.05 mg/kg/d) of bGH was infused, and did not increase further with higher doses. The changes in serum cholesterol concentration were similar to those of apo E. These results indicate that there are sex differences in the regulation of serum cholesterol and apo E concentrations by the pituitary and that these differences may be dependent on the sexually dimorphic secretion of GH. The pituitary regulation of the nonsexually differentiated apo B concentrations was similar in male and female rats and GH treatment decreased serum apo B concentrations independent of the mode of administration. Furthermore, the different time courses and dose-response relationships suggest different regulatory mechanisms for the regulation of apo E and apo B concentrations by GH in the rat.

Genetic polymorphism of the apolipoprotein B gene locus influences serum LDL cholesterol level in familial hypercholesterolemia

An XbaI restriction fragment length polymorphism (RFLP) within the coding region of the apolipoprotein B (apoB) gene has been found to be associated with serum cholesterol and triglyceride levels in several populations. Mutations in another genetic locus, the low density lipoprotein (LDL) receptor gene, give rise to familial hypercholesterolemia (FH), a disease characterized by hypercholesterolemia, tendon xanthomas and atherosclerosis. We determined the XbaI genotypes and serum lipoprotein levels of 120 unrelated patients with the heterozygous form of FH. A non-parametric analysis of variance showed a significant association between elevated serum total cholesterol concentration (P less than 0.05), serum LDL-cholesterol concentration (P less than 0.025) and the presence of the XbaI restriction site (X2 allele). Thus, patients homozygous for the presence of the XbaI restriction site (genotype X2X2, n = 28) had on average a 14% higher serum total cholesterol level and a 21% higher serum LDL-cholesterol level than those homozygous for the absence of this site (genotype X1X1, n = 29); patients heterozygous for the XbaI restriction site (genotype X1X2, n = 63) had intermediate serum total and LDL-cholesterol levels. No significant differences were seen in serum triglyceride or high-density lipoprotein (HDL)-cholesterol values between these patient groups. These data demonstrate that genetic polymorphism of the principal ligand for the LDL receptor, apoB, may contribute to serum cholesterol regulation, even in patients with grossly distorted cholesterol homeostasis.

Effects of Dietary Proteins on the Intestinal Synthesis and Transport of Cholesterol and Apolipoprotein A-I in Rats

Feeding a low-fat diet free of cholesterol to rats resulted in a low level of serum cholesterol and apolipoprotein A-I (apoA-I) when dietary protein was soybean protein as compared to casein. Since the small intestine is an important synthetic site for lipoproteins, the effects of dietary protein sources on the intestinal synthesis in vitro of cholesterol and apoA-I and the concentration of these components in the mesenteric lymph were studied. In rats fed a 1% fat diet, the apoA-I concentration in the lymph and the de novo synthesis of apoA-I in the small intestine segment were both low for animals fed a soybean protein diet as compared to a casein diet. The intestinal hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity was high in animals fed soybean protein, whereas the lymph cholesterol level was comparable. Even in rats fed a 5% fat diet, concentrations of serum cholesterol and apoA-I and lymphatic apoA-I were again significantly low for rats fed vegetable protein. These results indicate that the intestine plays an important role in the dietary protein-dependent regulation of serum cholesterol and apoA-I levels.

Pituitary growth hormone essential for regulation of serum cholesterol.

PITUITARY growth hormone was found to be essential in the normal regulation of the rat's serum cholesterol during a study of the cause(s) of the hypercholesterolaemia usually observed in the hypophysectomized rat.

INSULIN AND ATHEROMA

New information on carbohydrate and lipid metabolism has resulted in reappraisal of ideas of the underlying abnormalities in diabetes and atherosclerosis. It is noted that the incidence of diabetic arteriopathy has increased in spite of control of hyperglycemia and ketosis by insulin and that many nondiabetic persons with coronary artery disease have abnormalities or carbohydrate and lipid metabolism similar to those found in diabetics. Some patients secrete abnormally large amounts of insulin in response to dietary carbohydrate; these people have a particularly high incidence of vascular disease. Physicial excercise lowers insulin requirements. Synalbumin increased serum lipids in the forms of cholesterol triglycerides and the endogenous type of hyperlipidemia induced by dietary carbohydrate have been related to the incidence of coronary artery disease. The insulin response produced by the carbohydrate diet is related to the hepatic-triglyceride-secretion rate and is considered to be the primary cause of elevated serum-triglyceride. A similar mechanism is assumed for serum-cholesterol regulation. Hyperinsulinism is found in obesity in patients with hypertension and in some women who have been taking oral contraceptives for more than 1 year. These women also show elevated triglycerides and pre-beta-lipoprotein levels. It has been reported that these women also have an increased risk of vascular diseas e. The evidence incriminating insulin and carbohydrate is considered strong and would link atherosclerosis with diabetes obesity hyperlipidemia lack of physical exercise and possibly hypertention and use of contraceptive drugs.

Nongenetic prolonged serum cholesterol alteration induced by deoxyribonucleic acids.

Deoxyribonucleic acid (DNA) was prepared in a purified, undenatured form from a variety of mammalian sources. Preparations of DNA were assayed for their ability to induce a prolonged decrease in serum cholesterol and phospholipid levels in rabbits. Eighteen heterologous DNA preparations from five mammalian species and seven tissues lowered the serum cholesterol following a single injection, with no specificity observed as to species or tissue source of the DNA. Liver DNA was obtained from carefully selected "high-cholesterol" and "low-cholesterol" rabbits and assayed. The DNA from both homologous groups was equally effective in altering the serum lipids. Autologous DNA, prepared from each rabbit's own leukocytes, showed physiologic activity comparable to all other DNA preparations. The data indicate that the altered serum cholesterol regulation induced by heterologous, homologous and autologous DNA is not associated with the transfer of specific, genetic information. It is hypothesized that some DNA molecules in somatic cells may have metabolic regulatory roles associated with their polyelectrolyte physico-chemical properties.

Plasma deoxyribonuclease and the quantitative effects of injected DNA.

SummarySodium citrate injected into rabbits in amounts ranging from 9 μMoles to 150 μMoles produces a transient, significant in vivo inhibition of the plasma deoxyribonuclease. Injection of heterologous DNA into rabbits induces a prolonged decrease in total serum cholesterol. 30 μMoles of citrate and 0.1 mg DNA, injected together, are quantitatively as effective as 3 mg DNA in altering the serum cholesterol regulation. The citrate-induced deoxyribonuclease inhibition increased the physiologic activity of the injected DNA as much as 30-fold.