The metabolism of ketones,triglyceride and monoglyceride in livers of obese hyperglycaemic mice

Summary Some aspects of fat metabolism and ketogenesis have been investigated in obese hyperglycaemic mice, their non-obese littermates and normal mice. The proportion of total liver lipids was greatest in the obese mice, and the fatty acid composition of the liver total lipids showed a greatly reduced proportion of linoleic acid in the obese mice when compared with the other groups. Whole liver homogenates showed low rates of lipolysis of endogenous fat, but defatted liver homogenates showed a rapid lipolysis of added monoglyceride. Free fatty acid levels in the livers of obese mice were lower than in littermates or in normal mice. Total ketone production by liver slices from obese mice was lower than from normal mice. It was concluded that ketone production by the obese mice was related to liver free fatty acid levels rather than to total liver lipid.

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Der Stoffwechsel der Ketonkörper, der Triglycéride und der Monoglyceride in der Leber von fetten hyperglykämischen Mäusen

Zusammenfassung Einige Aspekte des Fettstoffwechsels und der Ketogenese wurden bei fetten hyperglykämischen Mäusen, ihren nichtfetten Wurfgeschwistern und normalen Mäusen untersucht. Der Anteil der Gesamtle-berlipide war am größten bei den fetten Mäusen; die Fettsäurenzusammensetzung der Lebergesamtlipide zeigte einen stark reduzierten Anteil der Linolsäure bei fetten Mäusen, wenn man sie mit den andern Gruppen verglich. Die Gesamtleber-Homogenate zeigten niedrige Quoten der Lipolyse endogenen Fettes, aber entfettete Leberhomogenate zeigten eine schnelle Lipolyse zugesetzter Monoglyceride. Der Spiegel der freien Fettsäuren in den Lebern fetter Mäuse war niedriger als bei den Wurfgeschwistern oder bei normalen Mäusen. Die Gesamtketonkörper-Produktion von Leberschnitten fetter Mäuse war niedriger als bei normalen Mäusen. Es wird der Schluß gezogen, daß die Ketonkörperproduktion fetter Mäuse eher auf das Niveau der freien Fettsäuren der Leber als auf die Gesamtleberlipide zu beziehen ist.

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Métabolisme des corps cétoniques, des triglycérides et des monoglycérides dans le foie de souris obèses hyperglycémiques

Résumé Certains des aspects du métabolisme des graisses et de la cétogenèse ont été examinés chez des souris hyperglycémiques obèses, leurs compagnons de portée non-obèses et chez des souris normales. La proportion des lipides totaux du foie s'est révélée comme étant la plus grande chez les souris obèses, et la composition d'acide gras des lipides totaux du foie a fait apparaotre chez les souris obèses une proportion d'acide linoléique qui était largement réduite par rapport aux autres groupes. Des homogénats de foie complet ont montré des taux de lipolyse de graisse endogene peu élevés, mais des homogénats de foie dégraissé ont montré une lipolyse rapide de monoglyceride ajoutée. Les taux d'acide gras libre dans les foies des souris obèses étaient plus bas que ceux de leurs compagnons de portée ou des souris normales. La production cétonique totale des tranches de foie provenant des souris obèses était moins élevée que celle des souris normales. Il en a été conclu que la production de corps cétoniques chez les souris obèses était liée aux taux d'acide gras libre du foie plutôt qu'aux lipides du foie total.

     

Endothelial dysfunction in streptozotocin-diabetic rats is not reversed by dietary probucol or simvastatin supplementation

Summary Oxidative stress and dyslipidaemia are key features of diabetes mellitus and may be involved in mediating the vascular endothelial dysfunction associated with this disease. The aim of this study was to examine the effect of dietary lipid-lowering and antioxidant agents on vascular endothelial function and oxidative stress. Diabetic male Sprague-Dawley rats (i. v. streptozotocin, 45 mg/kg) were fed for 4 weeks on a standard diet or on a diet supplemented with either the lipid-lowering antioxidant probucol (1 % w/w in diet) or the 3-hydroxy 3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor simvastatin (0.01 % w/w in diet). Responses to noradrenaline, acetylcholine, and sodium nitroprusside were assessed in small mesenteric arteries (mean internal diameter 300 ± 5 μm, n = 80) mounted on a small vessel myograph. Plasma concentrations of total cholesterol and triglycerides were significantly raised in standard-fed diabetic rats and significantly reduced in probucol and simvastatin-fed diabetic rats. 8-epi-prostaglandin (PG)F₂α, an indicator of oxidative stress, was raised in liver and aorta from diabetic rats compared to controls. Probucol supplementation reduced 8-epi-PGF₂α in aorta and liver of diabetic rats but increased 8-epi-PGF₂α content in plasma and aorta from control animals. The abnormal relaxation to acetylcholine in arteries from the diabetic rats (pEC₅₀ diabetic 6.763 ± 0.172 vs control 7.541 ± 0.175; p < 0.05) was not improved by probucol or simvastatin. These data, therefore, do not support a role for oxidative stress or dyslipidaemia in mediating the impaired ACh-induced endothelium-dependent relaxation of small mesenteric arteries from the streptozotocin-diabetic rat. [Diabetologia (1998) 41: 157–164] Received: 4 August 1997 and in revised form: 29 September 1997     

Metabolic Evaluation of HIV-Infected Patients Receiving a Regimen Containing Lopinavir/Ritonavir (Kaletra™)

Abstract

Purpose: We have analyzed retrospectively the evolution of metabolic parameters in a cohort of 159 HIV-infected patients taking a lopinavir/ritonavir-containing regimen during a mean period of 15 months. Method: This study was completed by an additional evaluation after strict 12 hours fasting of total cholesterol (TC), HDL-c, LDL-c, triglycerides (TG), glucose, and insulin levels in a subset of 100 patients from the cohort. Results: TC and TG levels increased early after introduction of lopinavir/ritonavir, but remained subsequently stable. After a median of 15 months, TC was greater than normal laboratory range in 46% of cases and TG levels were greater than normal laboratory range in 52% of cases. However, in nearly 90% of these cases, elevations were less than or equal to grade 2. These increases were dependant on CDC stage and lipid levels at lopinavir/ritonavir initiation. No impact on glucose metabolism was found. Conclusion: These results are particularly reassuring for the use of lopinavir/ritonavir in everyday practice.     

血脂与冠状动脉病变关系的探讨

目的　探讨血脂水平与冠状动脉病变的关系。方法　 2 2 8例进行过选择性冠状动脉造影的住院冠心病病人按冠状动脉狭窄程度积分为正常组、单支组、双支组、三支组四组。测定和比较血脂各项指标 TC、TG、HDL、L DL、apo A1 、apo B1 0 0 、L p(a)。结果　 L p(a)、HDL、apo A1 / apo B1 0 0 在各组之间存在着差异。L p(a)随着冠状动脉病变程度加重而增高 ,apo A1 / apo B1 0 0 随着冠状动脉病变程度加重而减少。 HDL与冠状动脉积分呈负相关 ,L p(a)与冠状动脉积分呈正相关。结论　 HDL和 L p(a)对预测冠状动脉病变有重要意义     

Westernized food habits and concentrations of serum lipids in the Japanese

To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese-Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese-Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia.     

From the Cover: Accumulation and enhanced cycling of polyphosphate by Sargasso Sea plankton in response to low phosphorus

Phytoplankton alter their biochemical composition according to nutrient availability, such that their bulk elemental composition varies across oceanic provinces. However, the links between plankton biochemical composition and variation in biogeochemical cycling of nutrients remain largely unknown. In a survey of phytoplankton phosphorus stress in the western North Atlantic, we found that phytoplankton in the phosphorus-depleted subtropical Sargasso Sea were enriched in the biochemical polyphosphate (polyP) compared with nutrient-rich temperate waters, contradicting the canonical oceanographic view of polyP as a luxury phosphorus storage molecule. The enrichment in polyP coincided with enhanced alkaline phosphatase activity and substitution of sulfolipids for phospholipids, which are both indicators of phosphorus stress. Further, polyP appeared to be liberated preferentially over bulk phosphorus from sinking particles in the Sargasso Sea, thereby retaining phosphorus in shallow waters. Thus, polyP cycling may form a feedback loop that attenuates the export of phosphorus when it becomes scarce, contributes bioavailable P for primary production, and supports the export of carbon and nitrogen via sinking particles.Phosphorus (P) is an essential element for all living organisms. However, P can be extremely scarce in open-ocean surface waters such as in the subtropical western North Atlantic (the Sargasso Sea), where soluble reactive P (SRP) concentrations are routinely <10 nmol⋅L⁻¹ and turnover rates are on the order of hours (1). Despite this scarcity, primary production by phytoplankton in the Sargasso Sea does not appear to be limited primarily by P (2, 3), reflecting the intensity of P recycling by the microbial community (4, 5) and the exquisite adaptations of marine phytoplankton to low P conditions, which remain to be fully characterized.Phytoplankton respond to low P by producing enzymes such as alkaline phosphatase to hydrolyze extracellular dissolved organic P molecules (4, 6, 7), increasing the affinity and rate of P uptake (8, 9) and reducing their inventory of P-containing biochemicals (1, 10). In contrast, when P is abundant, phytoplankton take up excess P and store it as a luxury reserve that is generally thought to be composed of polyphosphate (polyP) (10–12). This modulation of P-containing biochemicals results in basin-scale relationships between P availability and biomass carbon-to-phosphorus (C:P) ratios (13). Presently, the only class of molecules known to consistently contribute to these gradients in cellular P are lipids because P stress in phytoplankton triggers substitution of non–P-membrane lipids for phospholipids, such as the sulfolipid sulfoquinovosyldiacylglycerol (SQDG) for the phospholipid phosphatidylglycerol (PG) (1, 14). However, lipid substitution alone probably cannot account for the full range of C:P observed in the ocean, and yet an understanding of other biochemical drivers of the C:P gradient remains elusive. Further, it is unknown how changes in plankton biochemical composition influence the recycling of nutrients.Polyphosphate (polyP), a ubiquitous inorganic P polymer of three to hundreds of residues, has diverse physiological roles and complex dynamics in microbes. It is critical for surviving nutritional stress and stationary phase (15–17) but is also important for P homeostasis: microbes produce polyP when P is more abundant than required for growth, so-called luxury uptake, and break down this polyP store upon P stress (18). Moreover, if P-stressed cells experience a spike in P availability, they overproduce polyP in excess of luxury uptake levels, the so-called “overplus” response (19). Given these complex dynamics, it has been hypothesized that polyP might be either virtually absent, or particularly abundant, in oligotrophic marine systems (20).     

Ultra-high-resolution paleoenvironmental records via direct laser-based analysis of lipid biomarkers in sediment core samples

Marine microorganisms adapt to their habitat by structural modification of their membrane lipids. This concept is the basis of numerous molecular proxies used for paleoenvironmental reconstruction. Archaeal tetraether lipids from ubiquitous marine planktonic archaea are particularly abundant, well preserved in the sedimentary record and used in several molecular proxies. We here introduce the direct, extraction-free analysis of these compounds in intact sediment core sections using laser desorption ionization (LDI) coupled to Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). LDI FTICR-MS can detect the target lipids in single submillimeter-sized spots on sediment sections, equivalent to a sample mass in the nanogram range, and could thus pave the way for biomarker-based reconstruction of past environments and ecosystems at subannual to decadal resolution. We demonstrate that ratios of selected archaeal tetraethers acquired by LDI FTICR-MS are highly correlated with values obtained by conventional liquid chromatography/MS protocols. The ratio of the major archaeal lipids, caldarchaeol and crenarchaeol, analyzed in a 6.2-cm intact section of Mediterranean sapropel S1 at 250-µm resolution (∼4-y temporal resolution), provides an unprecedented view of the fine-scale patchiness of sedimentary biomarker distributions and the processes involved in proxy signal formation. Temporal variations of this lipid ratio indicate a strong influence of the ∼200-y de Vries solar cycle on reconstructed sea surface temperatures with possible amplitudes of several degrees, and suggest signal amplification by a complex interplay of ecological and environmental factors. Laser-based biomarker analysis of geological samples has the potential to revolutionize molecular stratigraphic studies of paleoenvironments.Microbial lipids in aquatic sediments reflect phylogeny, environmental conditions, and biogeochemistry of the water column in which they were produced. After sedimentation and because of the persistence of lipid structures in the sedimentary record, the information archived in these lipids remains available on geological time scales. Retrieval of this information from sediments and rocks has increasingly contributed to our understanding of past environments, microbial communities, and biogeochemical processes (e.g., refs. 1–5). Merged with the concept of molecular stratigraphy (2, 6), i.e., the analysis of selected biomarkers in solvent extracts of sediment samples in a stratigraphic framework, unique information can be gleaned regarding the temporal changes of past ecological and environmental conditions in aquatic systems. Because of analytical requirements, the temporal resolution is typically limited by centimeter-scale-sized samples, which, dependent on the depositional setting, tend to integrate time periods of decades to millennia, even in high-sedimentation settings such as the Santa Barbara Basin (e.g., refs. 4, 7, 8). In consequence, our knowledge of the temporal changes of the environmental and ecological history recorded by lipid biomarkers is rather coarse and based on long-term averages of their distributions in the sedimentary record.In this study we seek to extend this approach to ultra-high-resolution molecular stratigraphy. We focused on archaeal glycerol dialkyl glycerol tetraethers (GDGTs), which are produced by planktonic archaeal communities and are ubiquitous and persistent components in marine sediments (e.g., refs. 9, 10) with widely recognized potential for paleoenvironmental studies. The number of cycloalkyl rings in GDGTs (Fig. S1) appears highly sensitive to ecological and environmental factors such as phylogeny (ref. 5 and references therein), temperature (ref. 11 and references therein), or pH (12, 13). This sensitivity of GDGT composition to environmental and ecological factors has driven the development of multiple molecular proxies. Adaptation to temperature has been demonstrated in thermophilic cultures of archaea (e.g., ref. 14) and serves as concept for the reconstruction of paleo sea surface temperatures (SST) in sediments using the TEX₈₆ (tetraether index of 86 carbon atoms) (3), which is based on fossil lipids of planktonic archaea. This proxy has been used to characterize oscillations of SST in different geological episodes (e.g., refs. 8, 15, 16). Complications could arise from additional GDGT sources, e.g., allochthonous inputs of GDGT-bearing soils, lateral transport, in situ production, and/or recycling by sedimentary archaea (cf. refs. 5, 17). Relative GDGT distributions required for proxy calculations are obtained by HPLC atmospheric pressure chemical ionization mass spectrometry (HPLC/APCI-MS) of solvent extracts from gram-sized sediment samples (18, 19).To enhance temporal resolution of GDGT-based proxies, we explored the utility of laser desorption ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry (LDI FTICR-MS). In LDI, the impact of a pulsed laser beam on the sample leads to desorption, vaporization and ionization of the analytes, forming a cloud of charged molecules. An additional matrix is frequently applied to facilitate the generation of ions (matrix assisted laser desorption ionization [MALDI]). A complete understanding of underlying ionization mechanisms has not been achieved yet (20). LDI or MALDI are best known in the field of proteins or peptides and have also been successfully used in lipid research (21). The fact that LDI analysis can generate ions directly from the sample placed on a sample holder without time-consuming wet-chemical pretreatment while producing mass spectra from submillimeter-sized spots (as small as 10 µm) makes this technique particularly attractive for molecular stratigraphy. LDI may allow direct analysis of nanogram-sized samples on the surface of cut, intact sediment cores at ultra-high spatial resolution, equivalent to temporal resolution on the order of months to decades.We aimed to develop a technique that takes advantage of both the exquisite sensitivity and unequivocal molecular information of ultra-high-resolution mass spectrometry by FTICR-MS and the high spatial resolution of LDI within an intact and unaltered sedimentological context. The key steps of validation and implementation included (Fig. S2) (i) the detection of archaeal GDGTs, (ii) verification of results obtained by LDI FTICR-MS by parallel analysis using established HPLC/APCI-MS methods, and (iii) the examination of the first continuous high-resolution GDGT profile from a sediment core section of the eastern Mediterranean sapropel S1, which was deposited under anoxic conditions during the Holocene climatic optimum (HCO; refs. 22, 23). The data thus may provide an unprecedented view of the dynamic variations of both SST and ecological and environmental factors during sapropel formation.     

Global transcriptome response to ionic liquid by a tropical rain forest soil bacterium, Enterobacter lignolyticus

To process plant-based renewable biofuels, pretreatment of plant feedstock with ionic liquids has significant advantages over current methods for deconstruction of lignocellulosic feedstocks. However, ionic liquids are often toxic to the microorganisms used subsequently for biomass saccharification and fermentation. We previously isolated Enterobacter lignolyticus strain SCF1, a lignocellulolytic bacterium from tropical rain forest soil, and report here that it can grow in the presence of 0.5 M 1-ethyl-3-methylimidazolium chloride, a commonly used ionic liquid. We investigated molecular mechanisms of SCF1 ionic liquid tolerance using a combination of phenotypic growth assays, phospholipid fatty acid analysis, and RNA sequencing technologies. Potential modes of resistance to 1-ethyl-3-methylimidazolium chloride include an increase in cyclopropane fatty acids in the cell membrane, scavenging of compatible solutes, up-regulation of osmoprotectant transporters and drug efflux pumps, and down-regulation of membrane porins. These findings represent an important first step in understanding mechanisms of ionic liquid resistance in bacteria and provide a basis for engineering microbial tolerance.     

Antihyperlipidemic Effect of Curcumin and Tetrahydrocurcumin in Experimental Type 2 Diabetic Rats

Hyperlipidemia is an associated complication of diabetes mellitus. In the present study, we investigated the effect of tetrahydrocurcumin (THC), one of the active metabolites of curcumin on lipid profile in streptozotocin (STZ)-nicotinamide-induced diabetic rats. THC 80mg/kg body weight was orally administered to diabetic rats for 45 days, resulting in a significant reduction in blood glucose and a significant increase in plasma insulin in diabetic rats, which proved that THC possess an antidiabetic effect. THC also caused a significant reduction serum and liver cholesterol, triglycerides, free fatty acids, phospholipids, HMG CoA reductase activity, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. The decreased serum high-density lipoprotein (HDL) cholesterol in diabetic rats was also reversed toward normalization after the treatment. These biochemical observations were supplemented by histopathological examination of liver section. The effect was compared with curcumin (80 mg/kg body weight). The results showed that THC had antihyperlipidemic action in control and experimental diabetic rats. The antidiabetic and antihyperlipidemic effects of THC are more potent than those of curcumin at the same dose.