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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 55 records · Page 3Linked to original sources
PubMed1996

Dietary cholesterol feeding suppresses human cholesterol synthesis measured by deuterium incorporation and urinary mevalonic acid levels.

The objective of this study was to measure the response of cholesterol biosynthesis in subjects to three different amounts of dietary cholesterol: 50 (low), 350 (medium), and 650 (high) mg cholesterol per 2800 kcal. Individuals with low (n = 7), normal (n = 12), and elevated (n = 11) plasma cholesterol concentrations consumed in random order solid-food test diets (15%, 55%, and 30% of energy as protein, carbohydrate, and fat, respectively) at each dietary cholesterol level. The three diets were consumed for 4 weeks each, and each dietary phase was separated by a 4-week washout period. During the final week of each diet, 0.7 g D2O was given per kilogram of body water and deuterium incorporation into the erythrocyte cholesterol pool was measured for 24 hours. Urinary mevalonate levels were also determined in samples obtained during two consecutive 24-hour periods. Both techniques provided measurements of whole-body cholesterol biosynthesis. In all subjects the cholesterol synthesis rate as measured by deuterium incorporation was significantly lower (P < .05) after the transition from low- to medium- and low- to high-cholesterol diets. Urinary mevalonate excretion decreased after the change from the medium- to high- (P < .05) and low- to high- (P < .01) cholesterol diets. Although correspondence between the two methods was poor, they both indicated some suppression of cholesterol synthesis by dietary cholesterol. The response of cholesterogenesis to different amounts of dietary cholesterol was related to the rate of synthesis under depressed conditions of the low-cholesterol diet. These findings indicate modest downregulation of synthesis in response to dietary cholesterol in humans, independent of plasma cholesterol levels.

Adult↗
PubMed1995

Incorporation of dietary n-3 fatty acids into the fatty acids of human adipose tissue and plasma lipid classes.

The consumption of n-3 fatty acids from seafood has been related to a lower incidence of coronary artery disease. Adipose tissue composition has served as a biological marker of chronic ingestion of many dietary polyunsaturated fatty acids. However, the incorporation of n-3 fatty acids into the fat depots has not been studied in humans. Daily dietary supplementation with > or = 10 g n-3 fatty acids from fish oil for > 12 mo resulted in significantly greater 20:5n-3, 22:5n-3, and 22:6n-3 concentrations in fatty acids of adipose tissue, and a greater 20: 5n-3 fatty acid content in plasma lipid classes (cholesterol esters, phospholipids, and free fatty acids) of supplemented subjects compared with nonsupplemented control subjects. Combined values for all subjects indicated that fatty acid concentrations of n-3 plasma lipid classes, including 20:5n-3, 22:5n-3, 22:6n-3, and total n-3, significantly correlated with corresponding concentrations of fatty acids in adipose tissue. These findings indicate that the long-term ingestion of large amounts of n-3 fatty acids in humans resulted in their incorporation into the adipose tissue fatty acids. Incorporation of the fatty acids into adipose tissue warrants consideration for use in clinical studies requiring precise documentation of long-term n-3 fatty acid consumption.

Adipose Tissue↗
PubMed1995

Milk composition in women from five different regions of China: the great diversity of milk fatty acids.

Human milk samples were obtained from 146 lactating women living in five distinct geographic regions of the People's Republic of China. The regions were characterized as follows: pastoral, rural, urban 1, urban 2, and marine. Dietary information obtained on a subsample of women providing milk suggested distinct differences in the food availability in the five regions and the habitual diets of the lactating women studied. The milk concentration of docosahexaenoic acid (DHA) varied greatly (g/100 g total fatty acids): 0.44 +/- 0.29 (pastoral), 0.68 +/- 0.29 (rural), 0.88 +/- 0.34 (urban 1), 0.82 +/- 0.35 (urban 2), and 2.78 +/- 1.20 (marine region). Docosahexaenoic acid is critical for brain and retina development in the infant. Milk arachidonic acid (AA) ranged from 0.80 +/- 0.14 (rural) to 1.17 +/- 0.33 and 1.22 +/- 0.32 g/100 g fatty acids from the marine and pastoral regions. Arachidonic acid is associated with infant growth. The AA to DHA ratio (g/g) was highly variable also: 2.77 (pastoral), 1.18 (rural), 1.01 (urban 1), 1.23 (urban 2), and 0.42 (marine). The DHA concentration found in the milk of women from the marine region was twice as high as any reported previously, but was in a range similar to the amounts found in the milk of women fed fish oil. Seafood consumption by the women residing in the marine region is a likely contributor to the DHA concentration in their milk. These data illustrate the heterogeneity of the fatty acid composition of human milk and suggest a great influence of geography and the maternal diet on concentrations of DHA and AA in human milk.

Adult↗
PubMed1995

Role of dietary cholesterol in the optimal diet for the treatment of hypercholesterolemia.

OBJECTIVE: This paper discusses studies in which the effects of dietary cholesterol on the plasma concentrations of lipids and lipoproteins have been evaluated in adult human subjects including patients with hypo- and hypercholesterolemia. DESIGN: The dietary studies were conducted on an outpatient basis in the Clinical Research Center. Each dietary period was four weeks in duration and an adequate washout period was interposed between each dietary phase. SETTING: A university medical centre. PATIENTS: The participants in these studies were adult men or women with hypocholesterolemia, normal volunteers or patients with primary hypercholesterolemia. INTERVENTIONS: The dietary periods consisted of three separate dietary phases in which dietary cholesterol was a single variable. The diets contained 50 mg/day of cholesterol for the low cholesterol diet, 350 mg/day for the moderate cholesterol diet and 650 mg/day for the high cholesterol diet. RESULTS: Concentrations of total and low density lipoprotein (LDL) cholesterol increased in all three patient groups from the low cholesterol to the moderate cholesterol to the high cholesterol diet but the magnitude of increase in LDL cholesterol concentrations was greater in the patients with pre-existent hypercholesterolemia and least in the patients with hypocholesterolemia. In all three patients groups an increased intake of dietary cholesterol was associated with suppression of endogenous cholesterol biosynthesis as assessed by the urinary excretion of mevalonic acid. CONCLUSIONS: An increased intake of dietary cholesterol results in increases in the plasma concentrations of total and LDL cholesterol in patients with inherently low, normal or high concentrations of LDL cholesterol but the magnitude of increase is greatest in those patients with pre-existent hypercholesterolemia. These results support the view that restriction of dietary cholesterol leads to a reduction in the plasma concentrations of total and LDL cholesterol and is an appropriate recommendation for patients with known hypercholesterolemia or patients in whom medical recommendations call for a reduction in the plasma concentrations of total and LDL cholesterol.

Adult↗
PubMed1994

The lipids of slugs and snails: evolution, diet and biosynthesis.

There is a considerable gap in current knowledge of the lipid composition of snails and slugs, both of which belong to the phylum Mollusca. We have therefore analyzed the sterol and fatty acid compositions of three species of slugs and three species of snails. The sterols of slugs included eight different sterols: cholesterol contributed 76-85% of the total sterols, brassicasterol accounted for 4-13%; other sterols we identified were lathosterol, 24-methylene cholesterol, campesterol, stigmasterol, sitosterol and sitostanol. In contrast, snails contained two additional sterols, desmosterol and cholestanol. Of the polyunsaturated fatty acids in slugs, linoleic (18:2n-6) and arachidonic acids (20:4n-6) were the major n-6 fatty acids, while linoleic (18:3n-3) and eicosapentaenoic acids (20:5n-3) were the predominant n-3 fatty acids. Docosahexaenoic acid (22:6n-3), the end product in the n-3 fatty acid synthetic pathway and an important membrane fatty acid of mammals, fish and birds, was absent in both slugs and snails. However, the analogous product of n-6 fatty acid synthesis, 22:5n-6, was found in both snails and slugs. This raises speculation about preference for n-6 fatty acid synthesis in these species. Our data show the unique sterol and fatty acid compositions of slugs and snails, as well as similarities and differences in sterol composition between the two. The results between the two land mollusks are contrasted with those of marine mollusks, such as oysters, clams and scallops.

Animals↗
PubMed1994

Home cage behavior of rhesus monkeys with long-term deficiency of omega-3 fatty acids.

In an observational study with a blind observer, rhesus monkeys deficient in omega-3 (omega-3 or n-3) fatty acids initiated more bouts of stereotyped behavior in their home cages than monkeys fed a matched control diet abundant in omega-3 fatty acids. Locomotion bouts were also more frequent in deficient monkeys, but nonstereotyped locomotion did not differ. Both stereotyped behavior and the sum of all behavioral bouts were more frequent in 4-5-year-old than in 2-3-year-old monkeys, and stereotype decreased after meals in males but not females. The stereotyped behaviors associated with a deficit in omega-3 fatty acids were those typical of rhesus monkeys raised as partial social isolates or those whose surroundings have been disrupted.

Aging↗
PubMed1994

Elevated concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan Eskimos.

Eskimos living in rural southwestern Alaska depend on fish and marine mammals as major sources of subsistence food. Fatty acid concentrations in 80 Yupik Eskimos living in either a coastal or river village of southwestern Alaska were compared with those of non-Native control subjects. Concentrations of total plasma omega-3 fatty acids, eicosapentaenoic acid (20:5 omega-3), and docosahexaenoic acid (22:6 omega-3) were 4.3, 13, and 6.8 times higher, respectively, in Native participants than in non-Native control subjects. Concentrations of these fatty acids were higher in coastal-village than in river-village participants; concentrations paralleled consumption of marine mammal oil and marine fish. The ratios of eicosapentaenoic to arachidonic acid for adult coastal- and river-village participants were 1.16 and 0.70, respectively, 14 and 9 times those of non-Native adults, respectively. There was no increase in the mean bleeding times of Native participants of either village.

Adolescent↗
PubMed1994

Accretion of n-3 fatty acids in the brain and retina of chicks fed a low-linolenic acid diet supplemented with docosahexaenoic acid.

Diets low in alpha-linolenic acid may not support normal brain accretion of n-3 fatty acids. An n-3 fatty acid-deficient diet was fed to laying hens and the resulting deficient chicks were fed a low-linolenic acid diet based on corn oil, or the same diet supplemented with docosahexaenoic acid. Control chicks from soybean oil-fed hens were fed a soybean oil-based diet. The fatty acid composition of the chick brains, retinas, livers, and serum was determined after 0-4 wk. The corn oil diet did not reverse the deficiency but the combination of corn oil and docosahexaenoic acid rapidly restored brain and retinal concentrations of docosahexaenoic acid. Supplemented chicks, however, showed a slight lowering of arachidonic acid in the brain and serum. This study demonstrates that a low-linolenic acid diet without docosahexaenoic acid fails to support accretion of n-3 fatty acids in the nervous tissue of chicks.

Animals↗
PubMed1994

Incorporation of chylomicron fatty acids into the developing rat brain.

The developing brain obtains polyunsaturated fatty acids from the circulation, but the mechanism and route of delivery of these fatty acids are undetermined. 14C-labeled chylomicrons were prepared by duodenal infusion of [1-14C]16:0, [1-14C]18:2(n-6), [1-14C]18:3(n-3), or [1-14C]22:6(n-3) into adult donor rats, and were individually injected into hepatectomized 2-wk-old suckling rats. After minor correction for trapped blood in the brain, the incorporation of chylomicron fatty acids after 30 min was nearly half that of a co-injected free fatty acid reference. [1-14C]22:6(n-3)-labeled chylomicrons showed an average 65% greater incorporation than chylomicrons prepared from the other fatty acids. This apparent selectivity may have been partly due to lower oxidation of 22:6(n-3) in the brain compared to the other fatty acids tested, based on recovered water-soluble oxidation products. The bulk of the radioactivity in the brain was found in phospholipid and triacylglycerol, except that animals injected with [1-14C]22:6(n-3) chylomicrons showed considerable incorporation also into the fatty acid fraction instead of triacylglycerol. These data show that chylomicrons may be an important source of fatty acids for the developing rat brain.

Animals↗
PubMed1994

The relationship between serum lipoprotein(a) and insulinemia in healthy nondiabetic adult men.

OBJECTIVE: To test the hypothesis that variations in serum insulin concentrations and insulin action may influence serum concentrations of lipoprotein(a) [Lp(a)]. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of fasting serum insulin and Lp(a) concentrations were conducted in a group of 54 healthy adult men 23-61 years of age. Measures of dietary intake, exercise, smoking, alcohol ingestion, body mass index (BMI), fasting plasma lipoprotein lipid concentrations, and serum sex hormone and fasting glucose levels were also determined. RESULTS: The fasting serum concentrations of insulin and Lp(a) were negatively correlated (r = -0.339, P = 0.014) by univariate regression analysis. Several confounding variables were also significantly correlated with Lp(a) concentrations: testosterone (r = 0.348, P = 0.012), strenuous exercise (r = 0.287, P = 0.041), and BMI (r = -0.276, P = 0.050). As expected, these additional variables and serum insulin concentrations were highly interrelated. In a stepwise regression model, the serum insulin level was identified as the single best predictor of Lp(a) levels. Nearly 25% of the heterogeneity in serum concentrations of Lp(a) could be predicted by serum levels of insulin and testosterone, BMI, and the amount of strenuous exercise. CONCLUSIONS: The results of these studies have shown that serum concentrations of insulin and testosterone, BMI, and strenuous exercise appear to account for the majority of predicted nongenetic variability in serum levels of Lp(a). These observations suggest the possibility in this group of healthy men that serum concentrations of Lp(a) may be modulated by a complex interplay between insulin action, obesity, androgen levels, and strenuous exercise.

Adult↗
PubMed1994

Effect of dietary N-3 fatty acids upon the phospholipid molecular species of the monkey retina.

PURPOSE: To characterize the molecular species composition of ethanolamine glycerophospholipids (EGP) in the primate retina and to examine the effects of different dietary fats, the authors fed rhesus monkeys diets containing widely ranging amounts of n-3 fatty acids. METHODS: From birth, infant monkeys were fed either a control soybean oil diet, containing 8% of total fatty acids as 18:3 (n-3), or a safflower oil-based n-3 fatty acid deficient diet containing < 0.4% 18:3 (n-3). A subset of the n-3 deficient group was later repleted with 1.6% ethyl docosahexaenoate, 22:6 (n-3), starting at 10 months of age. Tissues were taken from all monkeys upon termination at 21 to 51 months of age. The diacyl, alkenylacyl, and alkylacyl EGPs were quantitated by high-pressure liquid chromatography (HPLC). RESULTS: Twenty-eight molecular species were identified in the retina of control monkeys. Ether phospholipids comprised 36% of the retinal ethanolamine glycerophospholipids. Species containing polyunsaturated fatty acids in both the sn-1 and sn-2 positions (dipolyenes) were present only in the diacyl subclass and comprised 16% of the total species. Species having n-3 fatty acids in the sn-2 position contributed 59%, 36%, and 70% of total species in the diacyl, alkenylacyl, and alkylacyl subclasses, respectively. In the molecular species of the n-3 fatty acid deficient monkeys, the major change was the loss of most of the 18:0-22:6(n-3) species and its partial replacement with 18:0-22:5(n-6). In contrast, the species 18:1-22:6(n-3) decreased only slightly, from 6.2% to 4.8% of total diacyl species. Although the total concentration of dipolyenes (15% to 20% of the total species) was not affected by diet, their fatty acid compositions were changed drastically. The dipolyene species 22:6(n-3)-22:6(n-3) nearly disappeared in the n-3 deficient monkeys. Concomitantly, two new species, 22:5(n-6)-22:6(n-3) and 22:5(n-6)-22:5(n-6), appeared at 2.6% and 2.0%, respectively. Deficient monkeys given the ethyl ester of 22:6(n-3) in the diet recovered to a near-normal molecular species composition, except in the ether lipids, in which 16:0-20:4 remained low. CONCLUSION: Diets of differing n-3 fatty acid content had profound qualitative and quantitative effects on the molecular species of retinal phospholipids, and the replacement of 22:6(n-3) by 22:5(n-6) in the retinas of n-3 deficient monkeys was asymmetric and functionally incomplete.

Animals↗
PubMed1993

Importance of diet in the treatment of familial hypercholesterolemia.

The principal goal of dietary treatment of heterozygous familial hypercholesterolemia (hFH) is the reduction of the plasma low density lipoprotein (LDL) cholesterol. This is best accomplished by enhancing the activity of LDL receptors and, at the same time, depressing liver synthesis of cholesterol. Both cholesterol and saturated fat down-regulate the LDL receptor and inhibit the removal of LDL from the plasma by the liver. Saturated fat down-regulates the LDL receptor, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is also important. The greater the flux of chylomicron remnants into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect LDL synthesis could be important. These include excessive calories (obesity) that enhance very low density lipoprotein (VLDL) and, hence, LDL synthesis, and weight loss and omega-3 fatty acids, which depress synthesis of VLDL and LDL. The optimal diet for treatment of children and adults has the following characteristics: cholesterol (100 mg/day), total fat (20% of kcal, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% kcal, 67% from starch), and protein (15% kcal). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18-21%. A new concept, the Cholesterol-Saturated Fat Index, allows people to evaluate any foodstuff for its potential to elevate the plasma LDL cholesterol level. It is an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Also, it contains significant amounts of antioxidants and fiber. Dietary therapy is the mainstay of treatment of hFH to which various drug therapies can be added.

Cholesterol, Dietary↗
PubMed1993

N-3 fatty acids from fish oil. Effects on plasma lipoproteins and hypertriglyceridemic patients.

In the experimental studies reported in this review, dietary n-3 fatty acids from fish and fish oil had profound hypolipidemic effects in normal subjects and in hypertriglyceridemic patients with combined hyperlipidemia (type II-b) and types IV and V hyperlipidemia. In these carefully controlled metabolic experiments, dramatic reductions occurred in plasma triglycerides and to a lesser extent in plasma total cholesterol. Reductions in VLDL, chylomicrons, remnants, LDL, apo B, and apo E were also noted. HDL changes varied from subject to subject. These plasma lipoprotein changes occurred in subjects with non-insulin-dependent diabetes mellitus as well, without deterioration of diabetic control. Similar results are reported in two other papers in this volume. Fish oil did not cause deterioration of diabetic control. Whereas the mechanism of the hypolipidemic action of the n-6 rich vegetable oils containing linoleic acid such as corn or safflower oil still remains obscure, the mechanism of the hypolipidemic action of the n-3 fatty acids in fish oil is well documented. The synthesis of triglyceride and VLDL in the liver is greatly reduced by n-3 fatty acids. At the same time, the turnover of VLDL in plasma is shortened. In another study, LDL production was decreased. Combined with other dietary manipulations, such as a reduction in saturated fat and dietary cholesterol, the use of n-3 fatty acids to treat hyperlipidemia, especially hypertriglyceridemia, appears to have a well-supported rationale. Fish oil combined with a low cholesterol, low saturated fat diet has been shown to produce complementary effects. Total plasma cholesterol and LDL cholesterol were lowered by the low cholesterol, low saturated fat diet, whereas plasma triglyceride and VLDL were decreased by the fish oil. In most situations, the use of fish oil supplements should be regarded as pharmacologic therapy, particularly effective in severe hypertriglyceridemic states (e.g., chylomicronemia). However, a lifelong diet rich in fish may be protective against atherosclerosis as well. Further studies are required to delineate exact doses and precise indications for the use of fish oil in different types of hyperlipidemias and to differentiate the effects, if any, of the two major n-3 fatty acids in fish oil, EPA and DHA. The hypolipidemic effects of n-3 fatty acids coupled with their known antithrombotic actions (secondary to changes in prostaglandin secretion, platelet function, inhibition of growth factors, and enhancement of endothelial-derived relaxation factor) appear to have an important potential role in the control of coronary heart disease and other atherosclerotic disorders. Moreover, fish oil may prevent the "chylomicronemia" syndrome of type V hyperlipidemia.

Dietary Fats, Unsaturated↗
PubMed1993

The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control.

Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.

Aged↗
PubMed1993

Individual effects of dietary saturated fatty acids and fish oil on plasma lipids and lipoproteins in normal men.

Fish ingestion is associated with lower mortality from coronary heart disease (CHD). However, in some Western populations whose diets are rich in saturated fatty acids (SFAs), CHD mortality is consistently high despite high fish consumption. To study this paradox, we fed six healthy men diets with two amounts of SFA (5% and 19% of energy) that also differed in total fat (25% and 39% of energy). Each fat amount was given with and without n-3 fatty acids (FAs) (2% of energy) for 3 wk. On both the low and high SFA diets the presence of n-3 FAs significantly lowered plasma total cholesterol, very-low-density-lipoprotein cholesterol, (high-density-lipoprotein cholesterol (HDL-C), total triglyceride, and very-low-density-lipoprotein triglyceride. Compared with the high SFA diet, the low SFA diet decreased total cholesterol, low-density-lipoprotein cholesterol, and HDL-C. No interaction of SFA and n-3 FA was found. These results indicate that dietary SFAs and n-3 FAs have independent mechanisms of actions on the plasma lipids and lipoproteins. Optimal plasma lipids were produced by the diet low in SFA and high in n-3 FA.

Adult↗
PubMed1993

Are dietary saturated, monounsaturated, and polyunsaturated fatty acids deposited to the same extent in adipose tissue of rabbits?

The objective of this study was to determine the effect that different dietary fatty acids would have on the fatty acid composition of adipose tissue. Thirty adult rabbits were starved 3-4 wk to deplete adipose tissue stores. They were then refed five different fats (linseed, rapeseed, cocoa butter, palm, and safflower oils) to regain initial body weights. The fatty acids of the adipose tissue, in general, reflected the diet. Positive correlations between the amount of the five commonly consumed fatty acids (palmitic, stearic, oleic, linoleic, and linolenic acids) in the diet and their deposition into the adipose tissue were observed. All polyunsaturated and monounsaturated fatty acids were well incorporated into the adipose tissue, even linolenic acid. The deposition of dietary saturated fatty acids (ie stearic acid) was limited. Our data showed that the fatty acids of dietary fats may greatly affect adipose fatty acid composition. Thus, adipose stores of essential fatty acids can be greatly augmented by diet.

Adipose Tissue↗