ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Obesity and lipoatrophy are major risks for insulin resistance, type 2 diabetes and cardiovascular diseases. The molecular links between adipocyte dysfunction and metabolic disorders were elusive until the discovery that adipose tissue operates as an endocrine organ and releases factors targeting a wide range of organs. This article attempts to review the more recent advances from research on the transcriptional control of adipogenesis and on new adipocyte-secreted proteins that have been proposed as molecular links between adipose tissue and insulin resistance.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Oxysterols are oxygenated derivatives of cholesterol that are intermediates in cholesterol excretion pathways. They may also be regarded as transport forms of cholesterol and introduction of an additional hydroxyl group facilitates flux of cholesterol across cell membranes and the blood-brain barrier. According to current concepts, oxysterols are also mediating a number of cholesterol-induced metabolic effects. The recent discovery of nuclear receptors with an affinity for oxysterols has given support to this concept. Nuclear receptors such as liver X receptor α do have a role in cholesterol homeostasis, but there is still only indirect evidence that oxysterols are the physiological ligands. In this overview we report some recent advancements in our knowledge about the origin and metabolic fate of the quantitatively most important oxysterols occurring in the circulation. In addition, we discuss the possibility that some of these oxysterols may activate liver X receptors and regulate cholesterol homeostasis.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Steroid hormones are believed to enter cells solely by free diffusion through the plasma membrane. However, recent work on the uptake of 25-hydroxyvitamin D3into the kidney has identified an endocytic pathway that is responsible for the delivery of this steroid to renal tissues. This finding led to a new perception that endocytosis may play an important role in the cell-type-specific targeting and uptake of steroid hormones. In the present review, we describe the molecular components (e.g. steroid carriers, endocytic receptors and intracellular transport proteins) that constitute this novel pathway for tissue-specific uptake of vitamin D metabolites.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid that is produced by a bio-hydrogenation process in the rumen, and thus is present in dairy products and ruminant meat. In this case the predominant isomer formed is 9cis,11trans. However, CLA includes 28 positional and geometrical isomers, of which only 9cis,11trans and 10trans,12cis have thus far been proven to possess biological activities. Both of these CLA isomers have been shown to undergo elongation and desaturation processes similar to those that occur with linoleic acid, maintaining the conjugated diene structure. There are evidences supporting the hypothesis that CLA metabolism may interfere with eicosanoid formation. Other metabolites with 16 carbon atoms (conjugated 16:2 and 16:3, which are probably derived from peroxisomal β-oxidation of CLA and its metabolites, respectively) have been detected. This suggests an efficient metabolism of CLA and its metabolites in peroxisomes, which might be linked to their capacity to activate peroxisome proliferator-activated receptors.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Recent literature provides a basis for understanding the behavioral, functional, and structural consequences of nutritional deprivation or disease-related abnormalities of n-3 polyunsaturated fatty acids. The literature suggests that these effects are mediated through competition between n-3 and n-6 polyunsaturated fatty acids at certain enzymatic steps, particularly those involving polyunsaturated fatty acid elongation and desaturation. One critical enzymatic site is a δ6-desaturase. On the other hand, an in-vivo method in rats, applied following chronic n-3 nutritional deprivation or chronic administration of lithium, indicates that the cycles of de-esterification/re-esterification of docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6) within brain phospholipids operate independently of each other, and thus that the enzymes regulating each of these cycles are not likely sites of n-3/n-6 competition.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Cytochrome P450s metabolize arachidonic acid to hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. These eicosanoids are formed in a tissue and cell-specific manner and have numerous biological functions. Of major interest are the opposing actions of hydroxyeicosatetraenoic and epoxyeicosatrienoic acids within the vasculature. Regio- and stereoisomeric epoxyeicosatrienoic acids have potent vasodilatory properties while 20-hydroxyeicosatetraenoic acid is a potent vasoconstrictor. Both effects are mediated through actions on large-conductance Ca2+-activated K+channels. Cytochrome P450-derived eicosanoids are also important in the regulation of ion transport, and have recently been shown to influence a number of fundamental biological processes including cellular proliferation, apoptosis, inflammation, and hemostasis. The formation of these functionally relevant eicosanoids is tightly controlled by the expression and activity of the cytochrome P450 epoxygenases and hydroxylases. In addition, soluble epoxide hydrolase catalyzes the hydrolysis of epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids, and the activity of this enzyme is a critical determinant of tissue epoxyeicosatrienoic and dihydroxyeicosatrienoic acid levels. The intracellular balance between epoxyeicosatrienoic, dihydroxyeicosatrienoic and hydroxyeicosatetraenoic acids influences the biological response to these eicosanoids and alterations in their levels have recently been associated with certain pathological conditions. The involvement of the cytochrome P450-derived eicosanoids in a wide array of biological functions and the observation that levels are altered in pathological conditions suggest that the enzymes involved in the formation and degradation of these fatty acids may be novel therapeutic targets.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

There are several potential mechanisms by which HDLs protect against atherosclerosis. One relates to the ability of HDLs to promote the efflux of cholesterol from macrophages. Another is the ability of HDLs to inhibit one of the earliest events in the development of atherosclerosis, namely the expression of vascular cell adhesion molecules in activated endothelial cells. This property has been reportedin vitroin studies with both native and reconstituted HDLs. The inhibitory activity of reconstituted HDLs is influenced by the phospholipid composition of the particles. An inhibition of endothelial cell adhesion molecule expression has also been observed in some (but not all) studies conductedin vivoin mice and pigs. The mechanism of this potentially anti-atherogenic effect of HDLs remains uncertain, as does its contribution to the cardioprotective effects of HDLsin vivo.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Imbalances of oxidative homeostasis and lipid peroxidation have been revealed as important factors involved in neurodegenerative disorders such as Alzheimer's disease. The brains of patients with Alzheimer's disease contain increased levels of lipid-peroxidation products such as 4-hydroxy-2-nonenal or acrolein, and enhanced lipid peroxidation can also be detected in cerebrospinal fluid and plasma from such patients. Recent research revealed that the interplay of transition metals, amyloid-β peptide and lipid peroxidation might be responsible for increased oxidative stress and cell damage in this disease. In particular, the contrasting roles of amyloid-β peptide, as a possible transition metal-chelating antioxidant for lipoproteins and a pro-oxidant when aggregated in brain tissue, has been the focus of discussion recently. In this context, lipid peroxidation has to be seen as an important part of the pathophysiological cascade in Alzheimer's disease, and its measurement in body fluids might serve as a therapy control for Alzheimer's disease and other neurodegenerative diseases.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Thia substituted fatty acids are saturated fatty acids which are modified by insertion of a sulfur atom at specific positions in the carbon backbone. During the last few years pleiotropic effects of the 3-thia fatty acid tetradecylthioacetic acid have been revealed. The biological responses to tetradecylthioacetic acid include mitochondrial proliferation, increased catabolism of fatty acids, antiadiposity, improvement in insulin sensitivity, antioxidant properties, reduced proliferation and induction of apoptosis in rapidly proliferating cells, cell differentiation and antiinflammatory action. These biological responses indicate that tetradecylthioacetic acid changes the plasma profile from atherogenic to cardioprotective. As a pan-peroxisome proliferator-activated receptor ligand, tetradecylthioacetic acid regulates the adipose tissue mass and the expression of lipid metabolizing enzymes, particularly those involved in catabolic pathways. In contrast, circumstantial evidences suggest that peroxisome proliferator-activated receptor-independent metabolic pathways may be of importance for the antioxidant, antiproliferative and antiinflammatory action of tetradecylthioacetic acid.

ISSN:0957-9672    

出版商:OVID    

年代:2002

数据来源: OVID