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Influence of the sex-linked dwarfing gene (dw) on the contribution of dietary lipid to yolk lipid synthesis.

1. The efficiency and time course of dietary fatty acid incorporation into lipids of egg yolk and abdominal adipose tissue was compared in "White Leghorn", normal (Dw) and dwarf (dw) laying hens at 56 weeks of age, using 14C labelled linoleic acid. 2. The sex-linked dwarfing gene, dw, was shown to reduce not only body weight and abdominal fat pad deposition, but also yolk production and the average clutch size. 3. Higher peak incorporation and total recovery of the linoleic acid radioactivity into yolk lipids, but lower label recovery into adipose tissue triglycerides were found in dwarf hens. 4. The higher esterification of the dietary linoleic acid in its native form into dwarf yolk triglycerides indicates that dwarf hens use more dietary lipids to synthesise yolk lipids but these results also suggest that the dw allele might reduce the lipogenic capacities of the liver and adipose tissue in laying hens.

Adipose Tissue↗

Lipid profile and bone paradox: higher serum lipids are associated with higher bone mineral density in postmenopausal women.

BACKGROUND: Previous studies suggest a relationship between cardiovascular disease (CVD) and osteoporosis; however, the mechanism of the relationship and whether serum lipids are positively or negatively associated with bone mineral density (BMD) are unclear. METHODS: We investigated the relationship among serum lipids, dietary saturated fat, BMD of various skeletal sites, and markers of bone turnover. This was a cross-sectional analysis in 136 Caucasian, healthy, postmenopausal women, who were not taking lipid-lowering medications or drugs affecting bone metabolism. BMD at multiple skeletal sites was assessed by DXA. Concentration of serum triglycerides, cholesterol, osteocalcin (OC), and undercarboxylated osteocalcin (UOC) and urinary cross-linked N-telopeptides were analyzed by routine methods. Saturated fat, total calcium (food and supplements), total vitamin K, alcohol, and energy intake were estimated using 3-day dietary records. Physical activity was assessed and used as a confounder with other anthropometric measurements. RESULTS: Serum triglycerides were positively related to femoral shaft BMD and serum cholesterol to total body BMD (p < 0.05). Also, subjects with serum triglycerides above the median had significantly higher BMD in femoral Ward's triangle than those below the median (p = 0.037, by ANCOVA). Subjects with a serum cholesterol level of > or =240 mg/dL (cutoff for increased risk for CVD) had significantly higher BMD at the total body and at all sites of the femur (except neck). There was no relationship between serum lipids and markers of bone turnover. Saturated fat intake was not associated with BMD of any skeletal site. CONCLUSIONS: These findings indicate that higher levels of serum triglycerides and cholesterol are positively associated with BMD of various skeletal sites. The mechanism of this association is not clear, and studies are needed to clarify this relationship.

Absorptiometry, Photon↗

Relation of changes in dietary lipids and weight, trial years 1-6, to changes in blood lipids in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

For men in the special intervention (SI) group of the Multiple Risk Factor Intervention Trial, the average decrease in serum total cholesterol was 16.9 mg/dL (6.7%); for men in the usual care (UC) group, the average decrease was 9.7 mg/dL (3.8%). The difference between the two groups for plasma total cholesterol was 6.2 mg/dL. Plasma low-density-lipoprotein (LDL) cholesterol decreased 10.6 mg/dL (6.6%) in SI men and 5.4 mg/dL (3.4%) in UC men. Mean weight losses were 3.0 lb (1.36 kg) and 0.1 lb (0.05 kg) for SI and UC men, respectively. Change in blood total cholesterol was directly related to baseline concentration; for men with serum total cholesterol > or = 220 mg/dL, those in the SI group decreased their total cholesterol by 7.8% (design goal: 10%) and those in the UC group by 4.8% (expected: 0%). Change in dietary lipid intake (summarized by the Keys score) for SI men was significantly related to changes in blood total cholesterol, LDL cholesterol, and triglyceride, but not to change in high-density-lipoprotein (HDL) cholesterol. Controlled for weight change, coefficients for Keys score change were smaller but remained significantly related to each blood lipid except HDL cholesterol. Weight loss was associated with favorable effects on all blood lipids. Influences of change in diet and weight on blood lipids were quantitatively less for hypertensive men for serum total cholesterol, HDL cholesterol, and triglyceride than for nonhypertensive men. Nonsmokers had greater decreases than smokers in blood total cholesterol, LDL cholesterol, and triglyceride.

Body Mass Index↗

Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk.

BACKGROUND: Blood lipid concentrations are causally related to the risk of coronary heart disease (CHD). Various associations between CHD risk and genes that moderately affect plasma lipid levels have been described, but previous studies have typically involved too few 'cases' to assess these associations reliably. METHODS: The present study involves 4685 cases of myocardial infarction (MI) and 3460 unrelated controls without diagnosed cardiovascular disease. Six polymorphisms of four 'lipid-related' genes were genotyped. RESULTS: For the apolipoprotein E epsilon2/epsilon3/epsilon4 polymorphism, the average increase in the plasma ratio of apolipoprotein B to apolipoprotein A(1) (apoB/apoA(1) ratio) among controls was 0.082 (s.e. 0.007) per stepwise change from epsilon3/epsilon2 to epsilon3/epsilon3 to epsilon3/epsilon4 genotype (trend P < 0.0001). The case-control comparison yielded a risk ratio for MI of 1.16 (95% CI: 1.06, 1.27; P = 0.001) per stepwise change in these genotypes. But, this risk ratio was not as extreme as would have been expected from the corresponding differences in plasma apoB/apoA(1) ratio between genotypes. Hence, following adjustment for the measured level of the plasma apoB/apoA(1) ratio, the direction of the risk ratio per stepwise change reversed to 0.83 (95% CI: 0.74, 0.92; P < 0.001). Similarly, for the apolipoprotein B Asn4311Ser and Thr71Ile polymorphisms, genotypes associated with more adverse plasma apolipoprotein concentrations were associated with significantly lower risk of MI after adjustment for the apoB/apoA(1) ratio. The B2 allele of the cholesteryl ester transfer protein TaqIb polymorphism was associated with a significantly lower plasma apoB/apoA(1) ratio, but with no significant difference in the risk of MI. Finally, the lipoprotein lipase Asn291Ser and T4509C (PvuII) polymorphisms did not produce clear effects on either the plasma apoB/apoA(1) ratio or the risk of MI. CONCLUSIONS: It remains unresolved why some of these genetic factors that produce lifelong effects on plasma lipid concentrations have significantly less than the correspondingly expected effects on CHD rates in adult life.

Adult↗

Dietary fish oil increases lipid mobilization but does not decrease lipid storage-related enzyme activities in adipose tissue of insulin-resistant, sucrose-fed rats.

Fish oil feeding has been shown to limit visceral fat accumulation in insulin-resistant rats. Our goal was to determine whether this finding is due to increased fat mobilization or decreased lipid storage. Adipocytes were isolated from rats fed for 3 wk a diet containing 57.5 g/100 g sucrose and 14 g/100 g lipids as either fish oil (SF) or a mixture of standard oils (SC); there was also a reference group (R). Substituting fish oil for standard oils protected rats from visceral fat hypertrophy, hypertriglyceridemia and hyperglycemia. The stimulation of lipolysis was greater in adipocytes isolated from SF-fed rats than in those from SC-fed rats. Fatty acid synthase (FAS) activity was markedly lower in the liver but not in the adipose tissues of rats fed SF. Lipoprotein lipase (LPL) activity was 2.2-fold higher in the adipose tissues but not in the muscle in rats fed the SF diet than in those fed the SC diet. The decrease in visceral fat in rats fed fish oil could be attributed to decreased plasma triacylglycerol concentration and/or increased lipid mobilization rather than to reduced lipid storage.

Adipose Tissue↗

Fatty acid content of plasma lipid fractions, blood lipids, and apolipoproteins in children fed milk products containing different quantity and quality of fat.

BACKGROUND: Differences in fatty acid content of plasma lipid fractions and serum lipid concentrations were investigated among young children fed different milk diets composed to achieve a recommended saturated fat intake. METHODS: Thirty-eight healthy children were randomly assigned to one of four feeding groups at 12 months: 1) low-fat milk (1.0 g/dL cow's milk fat); 2) standard-fat milk (3.5 g/dL cow's milk fat); 3) partially vegetable fat milk (3.5 gtat/dL fat; 50% vegetable fat: rapeseed oil); and 4) full vegetable-fat milk (3.5 gtat/dL fat; 100% vegetable fat: palm, coconut, and soy oil). Plasma fatty acids, blood lipids, and apolipoproteins were analyzed at 15 months, and dietary intakes at 12, 15, and 18 months. RESULTS: There were significantly lower percentage contributions of saturated fatty acids in plasma triglycerides in children fed low-fat milk or milk with 50% or 100% vegetable fat than in children fed standard-fat milk. Plasma polyunsaturated fatty acid levels were significantly higher in children fed milks with vegetable fat than in children fed standard-fat milk. Plasma saturated and polyunsaturated fatty acids in triglycerides most closely reflected dietary intake. Blood lipid concentrations were lower in children fed milk with 50% vegetable fat. CONCLUSIONS: Children fed milk with 50% or 100% vegetable fat, together with high vegetable-fat and low milk-fat dairy products have lower percentages of plasma saturated fatty acids and higher percentages of polyunsaturated fatty acids than children fed standard- or low-fat milk and dairy products.

Animals↗

Effects of various antihypertensive agents on lipid metabolism: alterations in the pattern of lipids synthesized from [14C]oleate in rat liver in vitro.

The effects of five antihypertensive agents on lipid biosynthesis from [1-14C]oleate were studied in rat liver minces. At a level of 1 mM, propranolol and prazosin increased the incorporation of [14C]oleate into diglycerides and cholesteryl esters by two- to fourfold and increased total phospholipid labeling by 20-30%. Chlorthalidone and metoprolol at 1 mM also stimulated the incorporation of [14C]oleate into phospholipids and diglycerides (20-50%) but did not affect its incorporation into triglycerides or cholesteryl esters. All four of the compounds statistically significantly inhibited the incorporation of [14C]oleate into phosphatidylcholine by 12-37% but stimulated incorporation into phosphatidylinositol by 17-95%. Nadolol differed from the other compounds in that it did not show selective effects but rather inhibited the incorporation of [14C]oleate into all lipid classes by approximately 50%. The data are discussed in terms of possible mechanisms involved in the lipid synthesis patterns and suggest the possibility that plasma lipid/lipoprotein changes observed in patients undergoing antihypertensive therapy may reflect, in part, altered hepatic lipid synthesis.

Animals↗

Lipid binding in rice nonspecific lipid transfer protein-1 complexes from Oryza sativa.

Nonspecific lipid transfer proteins (nsLTPs) facilitate the transfer of phospholipids, glycolipids, fatty acids and steroids between membranes, with wide-ranging binding affinities. Three crystal structures of rice nsLTP1 from Oryza sativa, complexed with myristic (MYR), palmitic (PAL) or stearic acid (STE) were determined. The overall structures of the rice nsLTP1 complexes belong to the four-helix bundle folding with a long C-terminal loop. The nsLTP1-MYR and the nsLTP1-STE complexes bind a single fatty acid while the nsLTP1-PAL complex binds two molecules of fatty acids. The C-terminal loop region is elastic in order to accommodate a diverse range of lipid molecules. The lipid molecules interact with the nsLTP1-binding cavity mainly with hydrophobic interactions. Significant conformational changes were observed in the binding cavity and the C-terminal loop of the rice nsLTP1 upon lipid binding.

Amino Acid Sequence↗

Serum lipids, biliary lipid composition, and bile acid metabolism in vegetarians as compared to normal controls.

Since dietary factors have been implicated in various diseases, such as coronary heart disease, gallstone formation and colonic cancer, possibly by affecting cholesterol and bile acid metabolism, we studied serum lipid levels, biliary lipid composition, cholic acid and deoxycholic acid kinetics in a group of young healthy male vegetarians and in age, sex and weight matched control subjects. Daily intake of nutrients was higher with respect to polyunsaturated fatty acids, carbohydrates and dietary fibre in the vegetarian group. Although mean serum lipid levels in the vegetarian were 8-28% lower than in the control subjects, differences were not statistically significant. Biliary lipid and biliary bile acid composition were similar in both groups. Bile acid kinetics, measured after simultaneous injection of [3H]cholic acid and [14C]deoxycholic acid, showed a slightly lower output of cholic acid and a slightly higher input of deoxycholic acid in the vegetarians, this causing a significantly (P less than 0.025) higher 7 alpha-dehydroxylation fraction (input deoxycholic acid divided by synthesis of cholic acid) in the vegetarians. Our results in young males suggest that bile acid conservation is associated with a vegetarian diet, but do not support the supposition that a vegetarian diet reduces deoxycholate formation.

Adult↗

Alpha 2-antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers.

Investigations were carried out to analyse the interactions of alpha 2-antagonists (yohimbine, idazoxan, SK & F-86,466) with human fat cell alpha 2-adrenoceptors. All the alpha 2-antagonists enhanced the lipolytic potencies of epinephrine with an order of potency: yohimbine greater than idazoxan greater than SK & F-86,466; the same order was also found in 3H-yohimbine competition studies on human fat cell membranes. The most potent agent, yohimbine, was administered orally in humans to define the conditions of appearance and the time-course of a putative lipid-mobilizing action. Oral yohimbine administration (0.2 mg kg-1) elevated plasma glycerol and non-esterified fatty acids in fasting healthy subjects without significant action on heart rate or blood pressure during the time-course of the experiment. The lipid-mobilizing action of yohimbine was reinforced during physical exercise, completely suppressed after a meal and partially blocked by administration of propranolol (0.5 mg kg-1; 60 min before yohimbine). Plasma norepinephrine concentrations were increased (40-50%) after oral yohimbine administration. The rise in plasma catecholamine concentration elicited by yohimbine was not modified by propranolol treatment. The lipid-mobilizing effect of yohimbine could be attributable to: (i) the increase in synaptic norepinephrine with a resultant increment in lipolysis by beta-adrenergic agonism; (ii) a decrease in alpha 2-adrenoceptor stimulation of human fat cell alpha 2-adrenoceptors; (iii) a blockade of presynaptic alpha 2-adrenoceptors. The use of highly selective alpha 2-antagonists will allow investigations into alpha 2-adrenoceptors, which may represent a novel locus for pharmacological intervention in lipid-mobilization strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis.

N-3 fatty acids were supplied to a 36-year-old female patient suffering from ulcerative colitis and severe steroid side-effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid [EPA], 4.2 g; docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n-3 lipid administration and declined during oral fish oil uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of protein-mediated lipid exchange in the study of membrane-bound enzymes. The lipid dependence of glucose-6-phosphatase.

The ability of liver lipid-exchange proteins to introduce foreign phospholipids into microsomes was used in a study of the lipid dependence of glucose-6-phosphatase. Supplementation of intact rat liver and hepatoma microsomes with exogeneous aminophospholipids prevents the decline of glucose-6-phosphatase activity during incubation, whereas the introduction of exogeneous phosphatidylcholine has no protective effect. On the contrary with deoxycholate-disrupted hepatoma microsomes, introduction of additional phosphatidylcholine causes activation while phosphatidylethanolamine has only little effect. The results are explained by assuming that the transport unit and the catalytic moiety of the glucose-6-phosphatase system have different lipid requirements, the activity of the former protein depending mainly on phosphatidylethanolamine and phosphatidylserine and that of the catalytic protein depending on phosphatidylcholine. In deoxycholate-disrupted liver microsomes (in which both the glucose-6-phosphatase activity and the phosphatidylcholine content are much higher than in hepatoma microsomes) incubation with phosphatidylcholine and lipid-exchange proteins alters neither the phospholipid composition nor the enzyme activity. THis suggests that the diminished activity of glucose-6-phosphatase in hepatomas may be partly due to a low level of phosphatidylcholine.

Animals↗

Biological activity of synthetic heptaacyl lipid A representing a component of Salmonella minnesota R595 lipid A.

A synthetic lipid A (preparation 516), containing seven acyl groups and representing one component of natural free lipid A of Salmonella minnesota R595, has been investigated for biological activity in a number of endotoxin test systems. It was found that the synthetic preparation was, in typical in vivo endotoxin tests (lethality, pyrogenicity, Shwartzman reactivity) as well as in its antigenicity and macrophage activation capacity, significantly less active than natural Salmonella lipid A. However, in other in vitro assay systems (B-cell mitogenicity, complement activation, Limulus amoebocyte lysate gelation) it expressed similar activity as Salmonella lipid A.

Animals↗

Identification and characterization of associated with lipid droplet protein 1: A novel membrane-associated protein that resides on hepatic lipid droplets.

Alcoholic and nonalcoholic liver steatosis and steatohepatitis are characterized by the massive accumulation of lipid droplets (LDs) in the cytosol of hepatocytes. Although LDs are ubiquitous and dynamic organelles found in the cells of a wide range of organisms, little is known about the mechanisms and sites of LD biogenesis. To examine the participation of these organelles in the pathophysiological disorders of steatotic livers, we used a combination of mass spectrometry (matrix-assisted laser desorption ionization-time of flight and LC-MS electrospray) and Western blot analysis to study the composition of LDs purified from rat liver after a partial hepatectomy. Fifty proteins were identified. Adipose differentiation-related protein was the most abundant, but other proteins such as calreticulin, TIP47, Sar1, Rab GTPases, Rho and actin were also found. In addition, we identified protein associated with lipid droplets I ALDI (tentatively named Associated with LD protein 1), a novel protein widely expressed in liver and kidney corresponding to the product of 0610006F02Rik (GI:27229118). Our results show that, upon lipid loading of the cells, ALDI translocates from the endoplasmic reticulum into nascent LDs and indicate that ALDI may be targeted to the initial lipid deposits that eventually form these droplets. Moreover, we used ALDI expression studies to view other processes related to these droplets, such as LD biogenesis, and to analyze LD dynamics. In conclusion, here we report the composition of hepatic LDs and describe a novel bona fide LD-associated protein that may provide new insights into the mechanisms and sites of LD biogenesis.

Amino Acid Sequence↗

Intravenous lipid infusion results in myocardial lipid droplet accumulation combined with reduced myocardial performance in heparinized rabbits.

The question addressed in this study was whether a relation between myocardial lipid droplet accumulation and depressed myocardial function existed following intralipid infusion for 45 min in open chest, anaesthetized rabbits. One group of rabbits (n = 8) received intralipid infusion whereas a control group (n = 8) received sodium chloride. Local myocardial performance was obtained by sonomicrometry and the fractional volume of myocardial lipid droplets was measured by morphometric methods. The fractional volume of lipid droplets was 0.667 +/- 0.116% in the intralipid group compared with 0.318 +/- 0.080% in the control group (P < 0.03). Cardiac output and stroke volume fell 26% (P < 0.0001) and 34% (P < 0.0001), respectively, as a result of intralipid infusion. However, myocardial blood flow obtained by radiolabelled microspheres remained unchanged. Local myocardial function was reduced for both segments after intralipid infusion; maximal systolic shortening was reduced from 15.63 +/- 1.45 to 12.07 +/- 1.55% (P < 0.002) in the circumferential segment and from 9.46 +/- 1.17 to 7.40 +/- 0.53% (P < 0.05) in the longitudinal segment. The end-diastolic length of the circumferential segment was reduced by 3% (P < 0.05) after intralipid infusion. The reduced end-diastolic length of circumferential segments together with unchanged left ventricular end-diastolic pressure might indicate reduced left ventricular end-diastolic compliance. We conclude that acute intralipid infusion in rabbits results in myocardial lipid droplet accumulation and depressed local myocardial function.

Animals↗

Lipid pattern of plasma in the presence of episcleral lipid deposits.

Examination of 40 subjects aged under 70 with episcleral lipid deposits revealed an abnormal serum lipid pattern in 48% of all. No correlation was noticed between the number of lipid deposits and the raised plasma lipid concentration or the distribution of fatty acids (saturated, unsaturated).

Adult↗

Lipid-itraconazole interaction in lipid model membranes.

Itraconazole, a lipophilic, fungal sterol-biosynthesis inhibitor, does not disturb membrane organization parameters measured by differential scanning calorimetry and infrared spectroscopy. Conformational analysis studies suggest that the molecular volume and the position of itraconazole in the lipid membrane is similar to that of dipalmitoyl phosphatidylcholine. The mean energy of interaction between itraconazole and the phospholipid is -60.6 kJ mol-1 whereas this energy in the pure lipid matrix is -54.3 kJ mol-1. The mean molecular area of itraconazole calculated by projecting the molecule on the lipid-water interface is equal to that occupied by the pure lipid (60 A2/molecule).

1,2-Dipalmitoylphosphatidylcholine↗

A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains.

The surface membrane of cells is studded with morphologically distinct regions, or domains, like microvilli, cell-cell junctions, and coated pits. Each of these domains is specialized for a particular function, such as nutrient absorption, cell-cell communication, and endocytosis. Lipid domains, which include caveolae and rafts, are one of the least understood membrane domains. These domains are high in cholesterol and sphingolipids, have a light buoyant density, and function in both endocytosis and cell signaling. A major mystery, however, is how resident molecules are targeted to lipid domains. Here, we propose that the molecular address for proteins targeted to lipid domains is a lipid shell.

Animals↗