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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obese and lean male Zucker rats were fed ad libitum on diets containing either 50 (L) or 200 (H) g/kg diet of either triolein (T) or sunflowerseed oil (S). The specific activity of the hepatic microsomal delta 9 desaturase enzyme was depressed in both lean and obese rats fed the HS diet compared with the other three diets. The fatty acid composition of liver and subcutaneous white adipose tissue lipids were consistent with a lower delta 9 desaturation activity in rats fed the H diets, particularly for the HS diet. In both genotypes, microsomal delta 9 desaturase activity and the ratio of 16:1/(16:0 + 16:1) fatty acids in liver lipids were inversely related to the proportion of 18:2 in liver lipid. Plasma insulin concentrations and rates of glucose-stimulated insulin release in vivo were higher in obese rats compared with lean rats, and plasma insulin levels were higher in rats fed S compared with T. There was no relationship between delta 9 desaturase activity and either plasma insulin concentration or rates of insulin release in vitro. These findings suggest that hepatic delta 9 desaturase activity of Zucker rats is responsive to changes in the proportion of 18:2 in liver lipids but is not affected by changes in insulin secretion.
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PMID:Effects of dietary triolein and sunflower oil on insulin release and lipid metabolism in Zucker rats. 351 42

1. The effects of food intake and the fatty acid composition of the diet on the hepatic stearoyl-CoA desaturase activity of obese-hyperglycaemic (ob/ob) mice were investigated. 2. Obese mice fed on a commercial mouse diet, ad libitum, had 6.5-fold more activity per liver cell than had lean mice. 3. On a diet containing 14% corn oil the activity was 65% less in obese mice and 62% less in lean mice compared with animals fed on the commercial diet. 4. Feeding with 14% saturated fat in the diet doubled the activity in lean mice compared with those on the commercial diet, but had no effect on the activity in obese mice. 5. Obese mice fed on the corn-oil diet contained a higher proportion of linoleic acid in the liver lipids than did lean mice fed on the commercial diet, but the acyl-CoA desaturase activity was 125% higher than in the lean mice. 6. Limiting the food intake of obese mice by pair-feeding with lean mice decreased their acyl-CoA desaturase activity when the animals were fed on the saturated-fat diet, but the activity remained 75% higher than in lean mice, whereas in obese mice pair-fed on the corn-oil diet the activity was the same as in lean mice. 7. During starvation the acyl-CoA desaturase activity in livers from obese mice decreased more slowly and proportionately less than in livers from lean mice. 8. It is concluded that increased substrate supply as a result of hyperphagia and not low concentration of linoleic acid is the main factor causing high acyl-CoA desaturase activity in obese mice.
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PMID:The regulation of hepatic stearoyl-coenzyme A desaturase in obese-hyperglycaemic (ob/ob) mice by food intake and the fatty acid composition of the diet. 612 73

High levels of dietary fat enhance the severity of certain cancers, obesity, and cardiovascular diseases in susceptible individuals usually after prolonged exposure. We have been developing methods for identifying and characterizing genes regulated by the level of dietary fat for the purpose of determining their role in diseases promoted by high levels of dietary fat, particularly cancer and atherosclerosis. Our protocol employs semi-purified diets of reproducible composition fed to normal inbred mice to obtain reagents for studying of molecular events that lead to pathology. Our early studies demonstrated that different levels of dietary fat cause the accumulation or change in expression of two genes, designated Lfm-1 and Lfm-2 (low fat mammary) in mouse mammary glands and selected other tissues. The Lfm-2 gene is stearoyl CoA desaturase, a gene known to be regulated by dietary fat and insulin levels. The Lfm-1 gene is highly similar to the e subunits of bovine and rat F1F0-ATPases. A Lfm-1 restriction fragment length polymorphism located on chromosome 8 is associated with atherosclerosis in certain inbred strains of mice warranting additional tests to determine whether it is involved in initiation or promotion of heart disease. The experimental approach has the potential for analyzing genes regulated by approximately 50 essential nutrients or other dietary constituents. A potential outcome of this research is the development of reagents which can be used to predict the risk of diet-related diseases in individuals.
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PMID:Diet-disease interactions at the molecular level: an experimental paradigm. 791 20

Modifications in dietary fat profile have been shown to affect body weight gain and adiposity. This may occur through changes in the partitioning between oxidation and storage and/or alterations in membrane structure, which may in turn influence metabolic rate. All the dietary fat classes are substrates for the biosynthetic elongase and desaturase enzymes. Obesity is associated with increased delta 9 desaturase activity, reduced delta 5 desaturase activity and perhaps reduced delta 6 desaturase activity. Dietary lipid profile can affect the activity of each of these enzymes. A number of possible mechanisms linking dietary fat subtypes with development of obesity are discussed, including modification of sodium potassium pump activity and alterations in mitochondrial proton leakage.
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PMID:Dietary fats, membrane phospholipids and obesity. 808 23

Chronic diseases develop in susceptible individuals following exposure to environmental conditions including high fat diets. Inbred strains of mice differing in susceptibility to atherosclerosis, diabetes, obesity and certain cancers are models for understanding the genetic basis and molecular mechanisms whereby diet influences these polygenic and multifactorial disorders. Expression sequence tags (EST) and disease quantitative trait loci (QTL) are also being identified with these strains. Reported here are comparisons of food intake, growth, nonfasting serum lipids and expression of mRNA for hepatic apolipoprotein E (ApoE), hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in a 2 x 2 x 2 design with C57BL/6J and BALB/cByJ mice fed semipurified diets with 4 or 20% saturated (coconut) or unsaturated (corn) oils for 4 mo. Histological studies of aortas and coronary arteries are also reported for these animals. After 4 mo, BALB/cByJ mice were significantly heavier and had significantly higher total serum cholesterol, HDL cholesterol and triglyceride concentrations in the fed state than C57BL/6J mice. Efficiency of utilizing dietary energy did not differ consistently between strains. Oil level affected serum total cholesterol, triglycerides and HDL cholesterol, which were significantly greater in mice fed high fat diets. Lpl and ApoE mRNA expression levels were not significantly affected by mouse strain, oil source or oil level. Scd1 mRNA expression, however, was significantly higher in C57BL/6J than in BALB/cByJ mice and was lower in all mice fed 20% compared with those fed 4% fat diets. Genes regulated differently by diet among strains with distinct susceptibility to diet-influenced disease may be associated with molecular pathways contributing to incidence or severity.
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PMID:Lipid level and type alter stearoyl CoA desaturase mRNA abundance differently in mice with distinct susceptibilities to diet-influenced diseases. 910 6

Excessive alcohol ingestion disturbs the metabolism of most nutrients. Although alcohol can lead to severe hypoglycemia, alcoholics are usually glucose intolerant, probably due to a inhibition of glucose-stimulated insulin secretion. Ethanol intake also leads to negative nitrogen balance and an increased protein turnover. Alcohol also alters lipid metabolism, causing a profound inhibition of lipolysis. Looking for an association between alcohol intake, nutrition, and alcoholic liver disease, we have observed a higher prevalence of subclinical histologic liver damage among obese alcoholics. Multivariate analysis in a large group of alcoholics has shown that obesity is an independent predictor of alcoholic liver disease. Other authors have reported that alcoholics with a history of obesity have a two to three times higher risk of having alcoholic liver disease than non-obese alcoholics. The possible explanation for this association is that the microsomal system, which plays an important pathogenic role in alcoholic liver disease, is induced in non-alcoholic obese subjects and alcoholics. Also, peripheral blood monocyte cells of obese alcoholics produce higher levels of interleukin-1, a cytokine that can contribute to liver damage. The ingestion of polyunsaturated fatty acids can also increase the damaging effects of alcohol on the liver, as has been demonstrated in rats subjected to continuous intragastric infusion of alcohol. Observations in human alcoholics have shown that liver damage is associated with a higher ratio of C:18:1/C:18:0 and a lower ratio of C:22:4/C:18:2 in liver lipids, consistent with an induction of delta 9 desaturase and an increased peroxidation of C:22:4.
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PMID:Nutritional and metabolic effects of alcoholism: their relationship with alcoholic liver disease. 1042 91

The lipid composition of cellular membranes is regulated to maintain membrane fluidity. A key enzyme involved in this process is the membrane-bound stearoyl-CoA desaturase (SCD) which is the rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids. A proper ratio of saturated to monounsaturated fatty acids contributes to membrane fluidity. Alterations in this ratio have been implicated in various disease states including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, hypertension, neurological diseases, immune disorders, and cancer. The regulation of stearoyl-CoA desaturase is therefore of considerable physiological importance and its activity is sensitive to dietary changes, hormonal imbalance, developmental processes, temperature changes, metals, alcohol, peroxisomal proliferators, and phenolic compounds. Two mouse and rat SCD genes (SCD1 and SCD2) and a single human SCD gene have been cloned and characterized. In the past several years we have studied the dietary influences on the genetic expression of the mouse stearoyl-CoA desaturase. The expression of the mouse SCD genes is regulated by polyunsaturated fatty acids and cholesterol at the levels of transcription and mRNA stability. Promoter elements that are responsible for the polyunsaturated fatty acid repression colocalize with the promoter elements for SREBP-mediated regulation of the SCD genes. It is the goal of this review to provide an overview of the genetic regulation of the stearoyl-CoA desaturase in response to dietary polyunsaturated fatty acids and cholesterol.
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PMID:Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. 1048 2

The degree of fatty acid unsaturation in cell membrane lipids determines membrane fluidity, whose alteration has been implicated in a variety of disease states including diabetes, obesity, hypertension, cancer, and neurological and heart diseases. Stearoyl-CoA desaturase (SCD) is a key rate-limiting enzyme in the synthesis of unsaturated fatty acids by insertion of a cis-double bond in the Delta9 position of fatty acid substrates. Palmitate and stearate are the preferred substrates, which are converted to palmitoleate and oleate, respectively. These monounsaturated fatty acids are the major constituents of cellular membrane phospholipids and triacylglycerol stores found in adipose tissue. Two mouse and rat SCD genes (SCD1 and SCD2) have been cloned and characterized. During the differentiation of 3T3-L1 preadipocytes into adipocytes, SCD1 and SCD2 mRNAs are induced concomitant with increased de novo synthesis of palmitoleate and oleate. The physiological significance of expressing the two isoforms in the adipocytes is currently unknown. In this review we discuss the role of the SCD isoforms in metabolism and the recent findings on the differential regulation of mouse SCD genes by the antidiabetic thiazolidinediones (TZDs), during preadipocyte differentiation.
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PMID:Regulation of stearoyl-CoA desaturase genes: role in cellular metabolism and preadipocyte differentiation. 1058 Nov 55

Stearoyl-CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1-/- mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1-/- mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage.
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PMID:Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. 1553 82

Stearoyl-CoA desaturase (SCD) (EC 1.14.99.5) is an endoplasmic reticulum-bound enzyme that catalyzes the delta9-cis desaturation of saturated fatty acyl-CoAs, the preferred substrates being palmitoyl- and stearoyl-CoA, which are converted to palmitoleoyl- and oleoyl-CoA, respectively. These monounsaturated fatty acids are used as substrates for the synthesis of triglycerides, wax esters, cholesteryl esters and membrane phospholipids. The saturated to monounsaturated fatty acid ratio affects membrane phospholipid composition and alteration in this ratio has been implicated in a variety of disease states including cardiovascular disease, obesity, diabetes, neurological disease, skin disorders and cancer. Thus, the expression of SCD is of physiological importance in normal and disease states. Several mammalian SCD genes have been cloned. A single human, three mouse and two rat are the best characterized SCD genes. The physiological role of each SCD isoform and the reason for having three or more SCD gene isoforms in the rodent genome are currently unknown. A clue as to the physiological role of the SCD, at least SCD1 gene and its endogenous products came from recent studies of asebia mouse strains that have a natural mutation in the SCD1 gene and a mouse model with a targeted disruption of the SCD1 gene. In this review we discuss our current understanding of the physiological role of SCD in lipid synthesis and metabolism.
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PMID:Role of stearoyl-coenzyme A desaturase in lipid metabolism. 1253 75


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