Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Avian lipogenesis was studied in the chicken hepatocarcinoma LMH cell line. The differentiated and lipogenic status of these cells was evidenced by the presence of the albumin mRNA as well as of some mRNA coding for enzymes involved in lipogenesis (acetyl-CoA carboxylase, fatty acid synthase, delta 9 desaturase) and for apoproteins (apoprotein B and A1). These results were further confirmed by the analysis of triglyceride synthesis and secretion rates in growing cells. A time course analysis showed that triglyceride metabolism was affected by cell density. Hormone responsiveness of triglyceride production was also analyzed. Insulin, triiodothyronine and glucagon to a lesser extent were shown to regulate lipogenesis of LMH cells. The results were compared with those obtained in primary cultures of chicken hepatocytes.
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PMID:Triglyceride synthesis and secretion and lipogenesis implicated gene expression in the chicken hepatocarcinoma cell line LMH. 940 72

Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the rate of gene transcription for a number of hepatic lipogenic and glycolytic genes, e.g., fatty acid synthase (FAS). In contrast, saturated and monounsaturated fatty acids have no inhibitory capability. The suppression of gene transcription resulting from the addition of PUFA to a high carbohydrate diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be recreated with hepatocytes cultured in a serum-free medium containing insulin and glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is independent of glucagon. While the nature of the intracellular PUFA inhibitor is unclear, it appears that delta-6 desaturation is a required step in the process. Recently, the fatty acid activated nuclear factor, peroxisome-proliferator activated receptor (PPAR) was suggested to be the PUFA-response factor. However, the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX). Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but had no effect on AOX. Thus, it appears that the PUFA regulation of gene transcription involves a PUFA-response factor that is independent from PPAR.
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PMID:Polyunsaturated fatty acid inhibition of fatty acid synthase transcription is independent of PPAR activation. 955 24

Adipocytes have highly specialized function of accumulating fat as stored energy that can be used during periods of food deprivation. The process of fat synthesis and development of adipose tissue are under hormonal and nutritional control. This review first describes transcription of the two critical enzymes involved in fat synthesis, fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase, is decreased to an undetectable level during fasting. Food intake, especially a high carbohydrate, fat-free diet, subsequent to fasting causes dramatic increase in transcription of these genes. Insulin secretion is increased during feeding, having a positive effect, whereas cAMP, which mediates the effect of glucagon which increases during fasting, has a negative effect on transcription of these genes. Using adipocytes in culture and in transgenic mice that express liciferase driven by the fatty acid synthase promoter, cis-acting and trans-acting factors that may mediate the transcriptional regulation were examined. Upstream stimulatory factors (USFs) that bind to -65 E-box are required for insulin-mediated transcriptional activation of the fatty acid synthase gene. This review next describes how pref-1 is a novel inhibitor of adipose differentiation and is a plasma membrane protein containing six EGF-repeats in the extracellular domain. Pref-1 is highly expressed in 3T3-L1 preadipocytes, but is not detectable in mature fat cells. Down regulation of pref-1 is required for adipose differentiation, and constitutive expression of pref-1 inhibits adipogenesis. Moreover, the ectodomain of pref-1 is cleaved to generate a biologically active 50 kDa soluble form. There are four major forms of membrane pref-1 resulting from alternate splicing, but two of the forms with a larger deletion do not produce biologically active soluble form, indicating that alternate splicing determines the range of action, juxtacrine or paracrine, of the pref-1.
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PMID:Regulation of fat synthesis and adipose differentiation. 959 78

1. The effects of dietary polychlorinated biphenyls (PCBs) (30-2000 ppm) on activities of gluconeogenic (phosphoenolpyruvate carboxykinase-PEPCK, and fructose 1,6-bisphosphatase-FdPase) and lipogenic enzymes (fatty acid synthase-FAS, ATP citrate lyase-ACL, malic enzyme-ME, glucose 6-phosphate dehydrogenase-G6PDH, and 6-phosphogluconate dehydrogenase-PGDH) were studied in livers of the female Sprague-Dawley and Wistar rat. 2. PCB amounts accumulating in the liver reflected the extent of dietary exposure. The Wistar strain was more sensitive to PCBs than the Sprague-Dawley strain. Of the Clophentype PCBs those containing 60 and 64% chlorine displayed the most pronounced effects. 3. Activities of gluconeogenic enzymes (PEPCK and FdPase) were dose-dependently decreased by PCBs, PEPCK being considerably more sensitive. This decrease was also found under conditions where the activity of PEPCK was induced (administration of adrenalin, glucagon or cAMP, feeding high protein diets, starvation). 4. Activities of lipogenic enzymes were induced by PCBs. The increase was much greater with ME, G6PDH and PGDH (up to 10-fold) than with FAS and ACL (approximately 2-fold). PCB effects were dose-dependent, but transient. 5. In cultured hepatocytes basal activities of lipogenic enzymes were induced by PCBs in the absence of hormones. With saturating levels of insulin or triiodothyronine, enzyme activities were also induced, but addition of PCBs resulted in an additive effect. 6. These results suggest that in the female rat PCBs can mimic the actions of certain hormones by affecting either hormone levels, hormone receptor systems or regulatory systems.
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PMID:Polychlorinated biphenyls affect the activities of gluconeogenic and lipogenic enzymes in rat liver: is there an interference with regulatory hormone actions? 962 50

The activities of critical enzymes in fatty acid and triacylglycerol biosynthesis are tightly controlled by different nutritional, hormonal, and developmental conditions. Feeding previously fasted animals high-carbohydrate, low-fat diets causes a dramatic induction of enzymes-such as fatty acid synthase (FAS) and mitochondrial glycerol-3-phosphate acyltransferase (GPAT)-involved in fatty acid and triacylglycerol synthesis. During fasting and refeeding, transcription of these two enzymes is coordinately regulated by nutrients and hormones, such as glucose, insulin, glucagon, glucocorticoids, and thyroid hormone. Insulin stimulates transcription of the FAS and mitochondrial GPAT genes, and glucagon antagonizes the insulin effect through the cis-acting elements within the promoters and their bound trans-acting factors. This review discusses advances made in the understanding of the transcriptional regulation of FAS and mitochondrial GPAT genes, with emphasis on elucidation of the mechanisms by which multiple nutrients and hormones achieve their effects.
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PMID:Nutritional and hormonal regulation of enzymes in fat synthesis: studies of fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription. 970 28

The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.
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PMID:ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. 1020 99

Oligofructose (OFS), a mixture of nondigestible/fermentable fructooligosaccharides, decreases serum triacylglycerol (TAG) when it is included in the standard, fiber-free or high fat diet of rats. This paper summarizes in vivo and in vitro data to establish a biochemical mechanism underlying the hypolipidemic effect of OFS. When OFS is added to the standard (carbohydrate-rich) diet of rats at the dose of 10 g/100 g, a TAG-lowering action occurs as a consequence of a reduction of de novo liver fatty acid synthesis. The depression in the activity of all lipogenic enzymes and fatty acid synthase mRNA suggests that OFS modifies the gene expression of lipogenic enzymes. Through its modulation of de novo lipogenesis, OFS can protect against liver lipid accumulation induced by providing 10% fructose-enriched water for 48 h. OFS also significantly decreases serum insulin and glucose, which are both known to participate in the nutritional regulation of lipogenesis. It also increases the intestinal production of incretins, namely, glucose-dependent insulinotropic peptide and glucagon-like peptide 1. This latter phenomenon results mainly from promotion of intestinal tissue proliferation by oligofructose fermentation end-products. Collectively, a link likely exists between the modulation of hormone and incretin production by OFS, and its antilipogenic effect.
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PMID:Biochemical basis of oligofructose-induced hypolipidemia in animal models. 1039 22

Epidemiological studies have suggested that repeated weight cycling over time may increase the risk of coronary heart disease. The mechanism involved remains poorly understood, but the change in lipid metabolism during weight cycling has been offered as a possible explanation. The present study investigated the effect of weight cycling on the size and fatty acid composition of rat fat pads as well as serum cholesterol, triglyceride, glucose, insulin, and glucagon in rats. Two consecutive weight cycles were induced by 40% energy restriction followed by ad libitum refeeding of either a moderate-fat (MF; 22% energy) or a high-fat (HF; 45% energy) diet. The lipogenic enzymes, including fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, pyruvate kinase, and lipoprotein lipase in the weight-cycled (WC) rats fed only the HF diet, yielded an overshoot of activities at the end of two weight cycles. These changes were accompanied by an 80% increase in the size of the adipocyte and a 40-50% increase in the size of perirenal and epididymal fat tissues in HF-WC rats. Regardless of whether the rats were fed the HF or MF diet, all WC rats showed a gradual reduction in linoleic and alpha-linolenic acid and an increase in palmitic, palmitoleic, and stearic acid in total body lipid. It is concluded that weight cycling in rats may promote body fatness if an HF diet is consumed and can significantly alter whole body fatty acid balance irrespective of whether they consumed an MF or HF diet. Most importantly, the weight cycling led to an overshoot or fluctuation of serum cholesterol, triglyceride, glucose, insulin, and glucagon. If weight cycling is associated with an increased risk of cardiovascular disease, then, part of the mechanism may involve the changes in these risk factors.
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PMID:Weight cycling-induced alteration in fatty acid metabolism. 1095 77

Several nondigestible but fermentable dietary carbohydrates are able to regulate lipemia and triglyceridemia in both humans and animals. The mechanism of their serum lipid-lowering effect remains to be elucidated. Oligofructose, which is a mixture of nondigestible and fermentable fructans, can decrease triacylglycerol in VLDL when given to rats. The triacylglycerol-lowering action of oligofructose is due to a reduction of de novo fatty acid synthesis in the liver through inhibition of all lipogenic enzymes, namely acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthase, malic enzyme (EC 1.1.1.40), ATP citrate lyase (EC 4.1.3.8), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). Our results suggest that oligofructose decreases lipogenic enzyme gene expression. Postprandial insulin and glucose concentrations are low in the serum of oligofructose-fed animals and this could explain, at least partially, the metabolic effect of oligofructose. Moreover, some events occurring in the gastrointestinal tract after oligofructose feeding could be involved in the antilipogenic effect of this fructan: the production of propionate through fermentation, a modulation of the intestinal production of incretins (namely glucose-dependent insulinotropic peptide and glucagon-like peptide-1), or the modification of the availability of digestible carbohydrates. Recent studies showed that the hypotriglyceridemic effect of fructans also occurs in humans.
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PMID:Effects of fructans-type prebiotics on lipid metabolism. 1115 57

An acute bout of prolonged exercise has been shown to decrease hepatic fatty acid synthase (FAS) mRNA and activity induced by high carbohydrate diets. The purpose of the current study was to examine the role of insulin in this exercise down-regulation of FAS. Sixty-four male Wistar rats were randomly divided into normal and streptozotocin (STZ)-treated diabetic groups. After being starved for 48 h and refed a high cornstarch (C) or fructose (F) diet for 10 h, one half of each group of rats was killed after an acute bout of prolonged exercise (E), while the other half of the group was killed in the rested state. STZ treatment suppressed plasma insulin and elevated plasma glucagon levels along with a severe hyperglycemia. FAS mRNA levels decreased by 60% (P < 0.05) with STZ treatment but were 250% higher in F-fed versus C-fed rats. E abolished F-induced FAS mRNA levels in both normal and STZ rats and decreased plasma glucose concentration in STZ rats (P < 0.05). F-fed normal rats showed twofold higher hepatic FAS activity than did C-fed normal rats and this dietary induction was abolished by STZ (P < 0.05). FAS activity in normal rats was not affect by E and was increased with E in STZ rats. Nuclear protein binding to the insulin response sequence was not affected by STZ or diet and increased with E (P < 0.05). Carbohydrate response element binding was greater with F- versus C-feeding (P < 0.05) but unaffected by E. E enhanced inverted CCAAT-box element binding regardless of diet and STZ. We conclude that although insulin status had a great influence on FAS gene expression, E-induced down-regulation of FAS mRNA was not mediated by altered insulin response sequence binding but primarily by increased inverted CCAAT-box element binding to the FAS promoter and/or decreased concentration of carbohydrate metabolites.
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PMID:Exercise down-regulates hepatic fatty acid synthase in streptozotocin-treated rats. 1153 63


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