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PubMed1997

Complementary insulin therapy improves blood glucose and serum lipid parameters in type 2 (non-insulin-dependent) diabetic patients. II. Effects on serum lipids, lipoproteins and apoproteins.

The aim of the present study was to evaluate the effects of complementary insulin therapy, consisting of a single dose of 1 to 8 units of shortacting insulin before each meal (4-6x daily) and sometimes at 02.30 h, on concentrations of serum lipids, lipoproteins and apoproteins in type 2 (non-insulin-dependent) diabetic patients, unsatisfactorily controlled either by oral hypoglycemic agents (OHA) or by longacting insulin 1-2x daily (INS 1-2). Compared means +/- SD. Patients on INS 1-2 (n = 82) had better baseline glycemic control than patients on OHA (n = 68) (HbAlc: 9.33 +/- 1.76% vs. 10.59 +/- 1.83%, p < 0.001 and fructosamine: 3.34 +/- 0.74 mmol/l vs. 3.85 +/- 0.84 mmol/l, p < 0.001) and serum triglyceride concentrations (3.03 +/- 2.05 mmol/l vs. 4.95 +/- 4.48 mmol/l, p < 0.001), in spite of longer duration of diabetes (13.35 +/- 8.07 years vs. 10.1 +/- 6.9 years, p < 0.001). After 8-10 weeks of complementary insulin therapy, OHA patients (n = 33) improved both the glycemic control (HbA1c: 10.5 +/- 1.78% vs. 9.0 +/- 1.75%, p < 0.001) and fructosamine: 4.0 +/- 0.85 mmol/l vs. 3.5 +/- 0.76 mmol/l, p < 0.001) and most of the lipid parameters (decreased serum triglyceride: 5.8 +/- 5.64 mmol/l vs. 3.6 +/- 4.69 mmol/l, p < 0.001, total cholesterol/HDL-cholesterol: 6.8 +/- 3.13 vs. 5.6 +/- 2.23, p < 0.01 and increased HDL-cholesterol: 1.0 +/- 0.30 mmol/l vs. 1.2 +/- 0.30 mmol/l, p < 0.001, apo AI: 1.6 +/- 0.26 g/l vs. 1.8 +/- 0.28 g/l, p < 0.001, LpAI particles: 0.6 +/- 0.1 g/l vs. 0.7 +/- 0.12 g/l, p < 0.001 and LDL-cholesterol/apo B: 2.1 +/- 0.67 vs. 2.7 +/- 0.67, p < 0.001). In patients previously on INS 1-2x (n = 34), complementary insulin therapy with reduced dose of insulin per day (49.6 +/- 22.5 U/d vs. 36.6 +/- 13.3 U/d, p < 0.001) did not further improve glycemic control but improved the number of proatherogenic and antiatherogenic lipoprotein particles (decreased apo B: 1.7 +/- 0.52 g/l vs. 1.5 +/- 0.94 g/l, p < 0.01, apo AI/Lp AI: 2.9 +/- 1.01 vs. 2.3 +/- 0.98, p < 0.01 and increased Lp AI particles: 0.6 +/- 0.10 g/l vs. 0.7 +/- 0.12 g/l, p < 0.0001); BMI also decreased (29.4 +/- 4.28 kg/m2 vs. 28.9 +/- 4.24 kg/m2, p < 0.05). These results demonstrate that complementary insulin therapy probably induces antiatherogenic lipoprotein changes in NIDDM patients previously treated by either OHA or INS 1-2x. Thus, this type of therapy should be used more often and start earlier, and should be preferred to longacting insulins.

Adult↗
PubMed2002

Profiling membrane lipids in plant stress responses. Role of phospholipase D alpha in freezing-induced lipid changes in Arabidopsis.

A sensitive approach based on electrospray ionization tandem mass spectrometry has been employed to profile membrane lipid molecular species in Arabidopsis undergoing cold and freezing stresses. Freezing at a sublethal temperature induced a decline in many molecular species of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) but induced an increase in phosphatidic acid (PA) and lysophospholipids. To probe the metabolic steps generating these changes, lipids of Arabidopsis deficient in the most abundant phospholipase D, PLD alpha, were analyzed. The PC content dropped only half as much, and PA levels rose only half as high in the PLD alpha-deficient plants as in wild-type plants. In contrast, neither PE nor PG levels decreased significantly more in wild-type plants than in PLD alpha-deficient plants. These data suggest that PC, rather than PE and PG, is the major in vivo substrate of PLD alpha. The action of PLD alpha during freezing is of special interest because Arabidopsis plants that are deficient in PLD alpha have improved tolerance to freezing. The greater loss of PC and increase in PA in wild-type plants as compared with PLD alpha-deficient plants may be responsible for destabilizing membrane bilayer structure, resulting in a greater propensity toward membrane fusion and cell death in wild-type plants.

Acclimatization↗
PubMed2003

Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity.

Blood platelets play an essential role in ischemic heart disease and stroke contributing to acute thrombotic events by release of potent inflammatory agents within the vasculature. Lysophosphatidic acid (LPA) is a bioactive lipid mediator produced by platelets and found in the blood and atherosclerotic plaques. LPA receptors on platelets, leukocytes, endothelial cells, and smooth muscle cells regulate growth, differentiation, survival, motility, and contractile activity. Definition of the opposing pathways of synthesis and degradation that control extracellular LPA levels is critical to understanding how LPA bioactivity is regulated. We show that intact platelets and platelet membranes actively dephosphorylate LPA and identify the major enzyme responsible as lipid phosphate phosphatase 1 (LPP1). Localization of LPP1 to the platelet surface is increased by exposure to LPA. A novel receptor-inactive sn-3-substituted difluoromethylenephosphonate analog of phosphatidic acid that is a potent competitive inhibitor of LPP1 activity potentiates platelet aggregation and shape change responses to LPA and amplifies LPA production by agonist-stimulated platelets. Our results identify LPP1 as a pivotal regulator of LPA signaling in the cardiovascular system. These findings are consistent with genetic and cell biological evidence implicating LPPs as negative regulators of lysophospholipid signaling and suggest that the mechanisms involve both attenuation of lysophospholipid actions at cell surface receptors and opposition of lysophospholipid production.

Amino Acid Sequence↗
PubMed2005

Modulation of apolipoprotein E structure by domain interaction: differences in lipid-bound and lipid-free forms.

Interaction of the amino- and carboxyl-terminal domains in apolipoprotein (apo) E, referred to as domain interaction, is predicted to be more pronounced in apoE4 than in apoE3 and to underlie the association of apoE4 with Alzheimer and cardiovascular diseases. However, direct physical proof for the domain interaction concept is lacking. To address this issue, fluorescence resonance energy transfer and electron paramagnetic resonance spectroscopy were used to probe the spatial proximity of the two domains of apoE. Both methods demonstrated that the two domains are closer in both lipid-free and phospholipid-bound apoE4 than in apoE3 as a result of domain interaction. In addition, as shown by electron paramagnetic resonance, the domains of apoE4 move apart to resemble more closely the distance in apoE3 when the isoforms are bound to triglyceride-rich emulsion particles. These results demonstrate that domain interaction is a structural property of apoE4 and that apoE adopts different conformations when complexed to different lipids.

Apolipoprotein E3↗
PubMed2000

Insights into the molecular organization of lipids in the skin barrier from infrared spectroscopy studies of stratum corneum lipid models.

In order to gain some insight into the molecular organization of lipids in the skin barrier we used Fourier transform infrared (FTIR) spectroscopy to investigate models of the stratum corneum (SC) containing deuterated hexadecanoic acid, cholesterol, and ceramide 2 or ceramide 5. In both models there is clear evidence of separate conformationally ordered domains of ceramide and fatty acids. In addition, these chains are packed in orthorhombic subcells at physiological temperatures. The ceramide headgroup behavior indicates distinct hydrogen bonding patterns between the ceramide 2 and ceramide 5 models. In the ceramide 2 model the amide I mode is split into two components suggesting strong transverse intermolecular hydrogen bonding between headgroups. In contrast, no amide splitting is observed for ceramide 5 although the amide frequencies are indicative of strong hydrogen bonding. These observations on the molecular organization of SC lipids are discussed in terms of skin barrier function.

Amides↗
PubMedDate not supplied

Mixed lipid aggregates containing gangliosides impose different 2H-NMR dynamical parameters on water environment depending on their lipid composition.

Water dynamics in samples of ceramide tetrasaccharide (Gg4Cer) vesicles and GM1 ganglioside micelles at 300:1 water/lipid mole ratio were studied by using deuterium nuclear magnetic resonance (2H-NMR). GM1 imposes a different restriction on water dynamics that is insensitive to temperatures either above or below its phase transition temperature or below the freezing point of water. The calculated correlation times are in the range of 10(-10) s, typical of water molecules near to the polar groups. Pure GM1 micelles have two distinct water microenvironments dynamically characterized. Their dynamic parameters remain constant with temperature ranging from -18 to 32 degrees C, but the amount of strongly associated water is modified. By contrast, a mixture of single soluble carbohydrates corresponding to GM1 polar head group does not preserve the dynamic parameters of water hydration when the temperature is varied. Incorporation of cholesterol or lysophosphatidylcholine into GM1 micelles substantially increases the mobility of water molecules compared with that found in pure GM1 micelles. The overall results indicate that both the supramolecular organization and the local surface quality (lipid-lipid interaction) strongly influence the interfacial water mobility and the extent of hydration layers in glycosphingolipid aggregates.

Gangliosides↗
PubMed1984

Acetylcholine receptor in planar lipid bilayers. Characterization of the channel properties of the purified nicotinic acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayers.

The properties of the channel of the purified acetylcholine receptor (AChR) were investigated after reconstitution in planar lipid bilayers. The time course of the agonist-induced conductance exhibits a transient peak that relaxes to a steady state value. The macroscopic steady state membrane conductance increases with agonist concentration, reaching saturation at 10(-5) M for carbamylcholine (CCh). The agonist-induced membrane conductance was inhibited by d-tubocurarine (50% inhibition, IC50, at approximately 10(-6) M) and hexamethonium (IC50 approximately 10(-5) M). The single channel conductance, gamma, is ohmic and independent of the agonist. At 0.3 M monovalent salt concentrations, gamma = 28 pS for Na+, 30 pS for Rb+, 38 pS for Cs+, and 50 pS for NH+4. The distribution of channel open times was fit by a sum of two exponentials, reflecting the existence of two distinct open states. tau o1 and tau o2, the fast and slow components of the distribution of open times, are independent of the agonist concentration: for CCh this was verified in the range of 10(-6) M less than C less than 10(-3)M. tau 01 and tau o2 are approximately three times longer for suberyldicholine ( SubCh ) than for CCh. tau o1 and tau o2 are moderately voltage dependent, increasing as the applied voltage in the compartment containing agonist is made more positive with respect to the other. At desensitizing concentrations of agonist, the AChR channel openings occurred in a characteristic pattern of sudden paroxysms of channel activity followed by quiescent periods. A local anesthetic derivative of lidocaine ( QX -222) reduced both tau o1 and tau o2. This effect was dependent on both the concentration of QX -222 and the applied voltage. Thus, the AChR purified from Torpedo electric organ and reconstituted in planar lipid bilayers exhibits ion conduction and kinetic and pharmacological properties similar to AChR in intact muscle postsynaptic membranes.

Animals↗
PubMed2005

Do lipids contribute to the lack of cardio-protective effect of binge drinking: alcohol consumption and lipids in three eastern European countries.

AIMS: The cardio-protective effect of moderate alcohol consumption is partly mediated by HDL cholesterol. However, epidemiological studies suggest that binge drinking may not be associated with reduced risk of heart disease; a possible explanation is that the relationship of blood lipids with binge drinking is different from that with moderate intake. We investigated this hypothesis in a population study in three eastern European countries. METHODS: We conducted a cross-sectional study in random population samples in Novosibirsk (Russia), Krakow (Poland) and Karvina (Czech Republic). A sub-sample of 282 men aged 45-64 years who provided a fasting blood sample were analysed. Annual alcohol intake and the frequency of heavy binge drinking (> or =140 g of ethanol per session) were estimated from a graduated frequency questionnaire. RESULTS: Annual intake of alcohol was positively associated with total and HDL cholesterol. After controlling for annual intake, the frequency of heavy binge drinking was associated with increased concentrations of total and HDL cholesterol. By combining annual intake and drinking pattern, we found that men consuming >8 l of alcohol per year who had a heavy binge at least once a month had the mean total, HDL and LDL cholesterol 1.69 (SE 0.35), 0.61 (0.11) and 0.97 (0.34) mmol/l, respectively, higher than non-drinkers; this resulted in more favourable ratios of total and LDL cholesterol relative to HDL cholesterol in frequent heavy bingers. Triglycerides were not related to alcohol intake or binge drinking. CONCLUSIONS: Blood lipids do not seem to explain the apparent lack of the cardio-protective effect of binge drinking reported in epidemiological studies.

Alcoholic Intoxication↗
PubMed1993

Protection against lethal endotoxemia by anti-lipid A murine monoclonal antibodies: comparison of efficacy with that of human anti-lipid A monoclonal antibody HA-1A.

The protective capacities of murine anti-lipid A monoclonal antibodies (MAbs) 8-2 and 26-20 were examined and compared with those of the human MAb HA-1A with respect to inhibition of lipopolysaccharide (LPS) priming of human polymorphonuclear leukocytes (PMNL) in vitro and protection against lethal endotoxemia in mice. HA-1A did not prevent the priming effect of either rough or smooth LPS, while MAb 26-20 effectively inhibited LPS priming of human PMNL. Also, both murine MAbs protected mice against an otherwise lethal challenge with rough Re LPS of S. minnesota R595 as well as with smooth LPS of E. coli O111:B4. HA-1A exerted no protection against the lethal effects of Re LPS in this in vivo model. The enhanced survival in mice by treatment with MAbs 8-2 and 26-20 was associated with decreased levels of LPS-induced tumor necrosis factor. Neutralization of lipid A as a mechanism of protection was strongly suggested by efficacious inhibition of LPS priming of human PMNL by MAbs 8-2 and 26-20 in vitro.

Animals↗
PubMed1983

Suppression of avian hepatic lipid metabolism by solvent extracts of garlic: impact on serum lipids.

The effects of garlic on lipid metabolism were examined in White Leghorn pullets that had been fed for 4 weeks either a control diet based on corn and soybean meal or an experimental diet containing either 3.8% garlic paste, a solvent extract (petroleum ether, methanol and water in sequence) of garlic paste, the residue or commercial garlic oil. Significant decreases in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (79-83%), cholesterol 7 alpha-hydroxylase (43-51%), fatty acid synthetase (17-29%) and in representative pentose-phosphate pathway (23-39%) activities accompanied the feeding of the petroleum ether-, methanol- and water-soluble fractions of garlic. Garlic paste and oil also suppressed these activities. Significant decreases in serum lipids occurred in response to the feeding of these garlic fractions: serum total cholesterol by 20-25%, low density lipoprotein cholesterol by 28-41% and triglycerides by 10-26%; but high density lipoprotein cholesterol failed to respond to these treatments. The residue remaining after solvent fractionation had little influence on these parameters. These findings were substantiated by a second study in which pullets of a commercial broiler line were fed the garlic fractions. The results confirm that garlic oil and odorous components of garlic lower cholesterol levels. An odorless water-soluble component of garlic also has this effect. The mechanism of the hypocholesterolemic action is at the level of the suppression of cholesterol biosynthesis.

Animals↗
PubMed1986

Effect of continuous and discontinuous intravenous or intragastric total parenteral nutrition in rats on serum lipids, liver lipids and liver lipogenic rates.

Lipogenesis and evidence of fat accumulation in the liver were investigated in adult male rats fed a hypertonic dextrose diet by continuous (C) and discontinuous (D) intravenous (IV) or intragastric (IG) infusion for 14 d. Rats fed by the IV and IG route were infused continuously and discontinuously (2100-0900) with 55 ml/d of a solution containing 30% dextrose and 2.72% amino acids plus vitamins and minerals. An orally (Or) fed group was fed 21.2 g of a solid diet, which provided an equivalent amount of calories and nitrogen as the infusion diet. Serum lipids, glucose, and insulin levels, de novo fatty acid synthesis in adipose tissue and liver, and the content of liver lipids were not altered by feeding the diet IV or IG. De novo lipogenesis was elevated in the livers of the continuously and discontinuously infused IV-or IG-fed rats compared with Or-fed rats. Fat accumulated in the livers of the rats infused continuously but not in the livers of the rats fed DIV, DIG or Or. Discontinuous feeding was associated with the mobilization of fatty acids that are necessary for lipoprotein formation and transport from the liver, which may explain, in part, why discontinuously infused rats do not develop fatty livers. These data indicate that cycling the total parenteral infusion may have clinical importance.

Adipose Tissue↗
PubMed2002

Synergy between cationic lipid and co-lipid determines the macroscopic structure and transfection activity of lipoplexes.

The large number of cytofectin and co-lipid combinations currently used for lipoplex-mediated gene delivery reflects the fact that the optimal cytofectin/co-lipid combination varies with the application. The effects of structural changes in both cytofectin and co-lipid were systematically examined to identify structure-activity relationships. Specifically, alkyl chain length, degree of unsaturation and the head group to which the alkyl side chain was attached were examined to determine their effect on lipoplex structure and biological activity. The macroscopic lipoplex structure was assessed using a dye-binding assay and the biological activity was examined using in vitro transfection in three diverse cell lines. Lipoplexes were formulated in three different vehicles currently in use for in vivo delivery of naked plasmid DNA (pDNA) and lipoplex formulations. The changes in dye accessibility were consistent with structural changes in the lipoplex, which correlated with alterations in the formulation. In contrast, transfection activity of different lipoplexes was cell type and vehicle dependent and did not correlate with dye accessibility. Overall, the results show a correlation between transfection and enhanced membrane fluidity in both the lipoplex and cellular membranes.

Animals↗
PubMed1990

Cancer mortality and lipid and lipoprotein levels. Lipid Research Clinics Program Mortality Follow-up Study.

The associations of serum lipid and lipoprotein levels with the risk of cancer mortality were assessed in 2,753 men and 2,476 women aged 40-79 years at baseline (1972-1976) who participated in the Lipid Research Clinics Program Mortality Follow-up Study through 1984. Seventy-nine cancer deaths occurred in men and 65 occurred in women during an average follow-up time of 8.4 years. Total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly inversely associated with overall cancer mortality in men, but no relation was observed in women. Neither high-density lipoprotein (HDL) cholesterol nor triglycerides were significantly related to total cancer mortality in either sex, although in women. HDL cholesterol was positively associated with risk of death from gynecologic cancers. Compared with men with higher cholesterol levels, the relative risk of death from colon cancer, adjusted for age, body mass, cigarette smoking, and alcohol consumption, was 5.20 (95 percent confidence interval (Cl) 1.61-16.8) in men with total cholesterol levels less than or equal to 187 mg/dl and 4.79 (95 percent CI 1.37-16.8) in those with LDL cholesterol levels less than or equal to 119 mg/dl. Death from smoking-related cancers was inversely related to baseline total cholesterol but not to LDL cholesterol. The absence of an association with HDL cholesterol, which has been shown to be lower in persons with clinically manifest malignancy, and evidence from survival curves suggest that the inverse relation in men is not due to preexisting disease.

Adult↗
PubMed1976

Post-traumatic blood lipid changes and fat embolism. Relation of post-traumatic blood lipid changes and fat embolism syndrome.

Serum cholesterol, triglycerides, phospholipids, and lipoprotein levels were studied by electrophoresis in 43 trauma patients with multiple fractures of the lower extremities and pelvis. Ten healthy volunteers were used for control studies. The fat embolism syndrome was diagnosed in eight of the 43 patients. The lipid values of all the trauma patients were lower than the control values. A decrease in cholesterol and phospholipids was observed in the fat embolism patients during 4 days; these changes were not observed in the other trauma patients. The triglycerides of all the trauma patients increased slowly over a period of 4 days. Changes in the lipoprotein fractions after the trauma were minor. An early increase in the alpha1 lipbrotein fraction was noted in the fat embolism patients simultaneously with a decrease in the pre-beta lipoprotein fraction; the values of the other trauma patients were at the control levels. Normalization was observed in 6 hours. The lipid concentrations of plasma and serum did not change with filtration with 1.2, 5, and 8mum Millipore filters. No differences were noted between the femoral and cubital vein samples.

Adult↗
PubMed2006

Serum lipid levels in relation to serum thyroid-stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromsø Study.

OBJECTIVE: To evaluate the relation between serum thyroid-stimulating hormone (TSH) and lipids. DESIGN: Cross-sectional epidemiological study, nested case-control study, and a placebo-controlled double-blind intervention study. METHODS: In the 5th Tromsø study serum TSH, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Subjects with subclinical hypothyroidism (SHT) and a matching control group were re-examined and apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) were also measured. Subjects with SHT were included in an intervention study with thyroxine supplementation for 1 year. RESULTS: A total of 5143 subjects from the 5th Tromsø study were included. A significant and positive correlation between serum TSH levels and serum TC and LDL-C levels were found in both genders. However, in the females this did not reach statistical significance after adjusting for age and BMI. The serum LDL-C were significantly higher and the Apo A1 levels significantly lower in 84 SHT subjects compared with 145 controls, and in the SHT females the TC levels were also significantly elevated. In the intervention study (32 subjects given thyroxine and 32 subjects given placebo), we observed a significant reduction in the Apo B levels after thyroxine medication. In those that at the end of the study had serum TSH levels in the range 0.2-2.0 mIU L(-1), the serum TC and LDL-C levels were also significantly reduced. CONCLUSIONS: There is a positive association between serum TSH levels and TC and LDL-C levels. These lipid levels are reduced with thyroxine treatment in subjects with SHT.

Adult↗
PubMed2000

Modulation of chemotaxis, O(2)(-) production and myeloperoxidase release from human polymorphonuclear leukocytes by the ornithine-containing lipid and the serineglycine-containing lipid of Flavobacterium.

The ornithine-containing lipid (OL) and the serineglycine-containing lipid (SGL) of Flavobacterium activated and modulated the functions of human polymorphonuclear leukocytes (PMNs). The OL and the SGL strongly activated fMet-Leu-Phe- and interleukin-8-induced chemotaxis of PMNs at the concentration of 0.1 microg ml(-1), and a synthetic OL also activated the function of PMNs. Further, the OL strongly activated O(2)(-) production from PMNs. Although the OL and the SGL slightly modulated myeloperoxidase release from PMNs, inhibition effects of their component fatty acid analogues were observed. O(2)(-) production-inducing activity is a common biological activity between the OL and bacterial lipopolysaccharides, but OL and SGL, unlike lipopolysaccharide, are potent activators of PMN chemotaxis.

Cells, Cultured↗
PubMed1969

Lipids of Drosophila: a newly detected lipid in the male.

A thin-layer chromatographic analysis of Drosophila melanogaster revealed a lipid to be found almost exclusively in the adult male. The compound or class of compounds having an R(F) close to that of methyl oleate is present in substantial amounts and is located predominantly in the ejaculatory bulb. It appears from genetic studies that the formulation of the lipid is not mediated by the Y chromosome.

Animals↗