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

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and its gene expression in adipocytes. In this study, we have shown the gene expression profile in human adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The human adipocytes were treated with 100 microM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. Based on the gene expression profile, we demonstrated the significant changes of adipocytokine expression (up-regulation of adiponectin and down-regulation of plasminogen activator inhibitor-1 and interleukin-6). Some of lipid metabolism related genes (uncoupling protein2, acylCoA oxidase1 and perilipin) also significantly induced in both common the C3G or Cy treatment groups. These studies have provided an overview of the gene expression profiles in human adipocytes treated with anthocyanins and demonstrated that anthocyanins can regulate adipocytokine gene expression to ameliorate adipocyte function related with obesity and diabetes that merit further investigation.
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PMID:Microarray profiling of gene expression in human adipocytes in response to anthocyanins. 1648 47

Central (visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than is peripheral [subcutaneous (sc)] obesity, but the underlying mechanism for this pathophysiological difference is largely unknown. To understand the molecular basis of this difference, we sequenced 10,437 expressed sequence tags (ESTs) from a human omental fat cDNA library and discovered a novel visceral fat depot-specific secretory protein, which we have named omentin. Omentin ESTs were more abundant than many known adipose genes, such as perilipin, adiponectin, and leptin in the cDNA library. Protein sequence analysis indicated that omentin mRNA encodes a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. Northern analysis demonstrated that omentin mRNA was predominantly expressed in visceral adipose tissue and was barely detectable in sc fat depots in humans and rhesus monkeys. Quantative real-time PCR showed that omentin mRNA was expressed in stromal vascular cells, but not fat cells, isolated from omental adipose tissue, with >150-fold less in sc cell fractions. Accordingly, omentin protein was secreted into the culture medium of omental, but not sc, fat explants. Omentin was detectable in human serum by Western blot analysis. Addition of recombinant omentin in vitro did not affect basal but enhanced insulin-stimulated glucose uptake in both sc (47%, n = 9, P = 0.003) and omental (approximately 30%, n = 3, P < 0.05) human adipocytes. Omentin increased Akt phosphorylation in the absence and presence of insulin. In conclusion, omentin is a new adipokine that is expressed in omental adipose tissue in humans and may regulate insulin action.
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PMID:Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. 1653 7

Human fat cell lipolysis was considered until recently to be an exclusive cAMP/protein-kinase A (PKA)-regulated metabolic pathway under the control of catecholamines and insulin. Moreover, exercise-induced lipid mobilization in humans was considered to mainly depend on catecholamine action and interplay between fat cell beta- and alpha2-adrenergic receptors controlling adenylyl cyclase activity and cAMP production. We have recently demonstrated that natriuretic peptides stimulate lipolysis and contribute to the regulation of lipid mobilization in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) stimulate lipolysis in human isolated fat cells. Activation of the adipocyte plasma membrane type A guanylyl cyclase receptor (NPR-A), increase in intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels and activation of hormone-sensitive lipase mediate the action of ANP. ANP does not modulate cAMP production and PKA activity. Increment of cGMP induces the phosphorylation of hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I (cGK-I). Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans. Physiological relevance of the ANP-dependent pathway was demonstrated in young subjects performing physical exercise. ANP plays a role in conjunction with catecholamines in the control of exercise-induced lipid mobilization. This pathway becomes of major importance when subjects are submitted to chronic treatment with a beta-blocker. Oral beta-adrenoceptor blockade suppresses the beta-adrenergic component of catecholamine action in fat cells and potentiates exercise-induced ANP release by the heart. These findings may have several implications whenever natriuretic peptide secretion is altered such as in subjects with left ventricular dysfunction, congestive heart failure and obesity.
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PMID:[Natriuretic peptides: a new lipolytic pathway in human fat cells]. 1659 2

Exogenous FA cause lipid accumulation in pre-adipocytes. We investigated whether the fat cells thus formed are metabolically distinct from adipocytes differentiated with standard methylisobutylxanthine, dexamethasone, and insulin (MDI) hormonal cocktail by comparing their expression of adipogenic genes, accumulation of TAG, lipogenesis, lipolysis, glucose uptake, and the effects of insulin on selected metabolic activities. Cells exposed to oleate began to accumulate TAG in parallel or prior to the induction of adipogenic genes, whereas cells treated with MDI expressed adipogenic genes before TAG accumulation. Oleate-treated fat cells also showed exaggerated basal lipolysis and weak response to insulin in both lipolysis regulation and glucose uptake. These findings were associated with increased basal phosphorylation of perilipin, increased Glut-1 but decreased Glut-4 expression, and reduced insulin-induced Akt phosphorylation. We suggest that this unique fat cell phenotype might be a mimetic of what can happen to fat cells formed in vivo under the influence of circulating FA and might be a useful model for in vitro studies of obesity-related insulin resistance in adipocytes.
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PMID:Oleate-induced formation of fat cells with impaired insulin sensitivity. 1671 1

In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the biguanide, metformin, exerts its antihyperglycemic effect by improving insulin sensitivity, which is associated with decreased level of circulating free fatty acids (FFA). The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-alpha (TNF-alpha), a cytokine largely expressed in adipose tissue, stimulates chronic lipolysis, which may be associated with increased systemic FFA and insulin resistance in obesity and NIDDM. In this study, we examined the role of metformin in inhibiting lipolytic action upon various lipolytic stimulations in primary rat adipocytes. Treatment with metformin attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 and reversing the downregulation of perilipin protein in TNF-alpha-stimulated adipocytes. The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by metformin. A high concentration of glucose in the adipocyte culture promoted the basal rate of glycerol release and significantly enhanced the lipolytic action stimulated by either TNF-alpha or isoproterenol. Metformin not only inhibits the basal lipolysis simulated by high glucose, but also suppresses the high glucose-enhanced lipolysis response to TNF-alpha or isoproterenol. The antilipolytic action in adipocytes could be the mechanism by which cellular action by metformin reduces systemic FFA concentration and thus improves insulin sensitivity in obese patients and the hyperglycemic conditions of NIDDM.
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PMID:Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-alpha or isoproterenol. 1690 33

Humans have evolved mechanisms of efficient fat storage to survive famine, but these mechanisms contribute to obesity in our current environment of plentiful food and reduced activity. Little is known about how animals package fat within cells. Five related structural proteins serve roles in packaging fat into lipid droplets. The proteins TIP47, S3-12, and OXPAT/MLDP/PAT-1 move from the cytosol to coat nascent lipid droplets during rapid fat storage. In contrast, perilipin and adipophilin constitutively associate with lipid droplets and play roles in sustained fat storage and regulation of lipolysis. Different tissues express different complements of these lipid droplet proteins. Thus, the tissue-specific complement of these proteins determines how tissues manage lipid stores.
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PMID:A proposed model of fat packaging by exchangeable lipid droplet proteins. 1696 4

Perilipins are the proteins associating with the lipid droplets in adipocytes and steroidogenic cells. Unphosphorylated perilipins coat the surface of intracellular lipid droplets to form a barrier that prevents lipase from accessing to triacylglycerol core, thus suppressing lipolysis. Upon activation of protein kinase A (PKA), two proteins, hormone-sensitive lipase (HSL) and perilipins, are phosphorylated. The phosphorylated perilipin is required for inducing the translocation of HSL from the cytosol to the lipid droplets of adipocytes and is essential for the initiation of lipolytic reaction. It is proposed that phosphorylation of perilipin is a key step for the activation of lipolytic cascade via PKA and ERK signaling pathways. Dysregulation of perilipin involves in the pathogenesis of obesity, diabetes and atherosclerosis.
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PMID:[Perilipin associated with lipid droplets regulates lipolysis]. 1700 29

The effects of oral treatment with Aralox phytopreparation containing Aralia mandshurica (Araliaceae) and Engelhardtia chrysolepis (Juglandaceae) extracts on some parameters of lipid metabolism was studied in women with nondiabetic obesity receiving low-caloric diet. Our randomized placebo-controlled study comprising 32 volunteers showed that aralox treatment led to a decrease in total body weight and fat weight, reduced perilipin content in adipocytes and plasma triglyceride content, and stimulated activity of hormone-sensitive lipase.
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PMID:Effects of Aralia mandshurica and Engelhardtia chrysolepis extracts on some parameters of lipid metabolism in women with nondiabetic obesity. 1707 56

The insulin/insulin-like growth factor signalling (IIS) cascade performs a broad range of evolutionarily conserved functions, including the regulation of growth, developmental timing and lifespan, and the control of sugar, protein and lipid metabolism. Recently, these functions have been genetically dissected in the fruit fly Drosophila melanogaster, revealing a crucial role for cell-surface activation of the downstream effector kinase Akt in many of these processes. However, the mechanisms regulating lipid metabolism and the storage of lipid during development are less well characterized. Here, we use the nutrient-storing nurse cells of the fly ovary to study the cellular effects of intracellular IIS components on lipid accumulation. These cells normally store lipid in a perinuclear pool of small neutral triglyceride-containing droplets. We find that loss of the IIS signalling antagonist PTEN, which stimulates cell growth in most developing tissues, produces a very different phenotype in nurse cells, inducing formation of highly enlarged lipid droplets. Furthermore, we show that the accumulation of activated Akt in the cytoplasm is responsible for this phenotype and leads to a much higher expression of LSD2, the fly homologue of the vertebrate lipid-storage protein perilipin. Our work therefore reveals a signalling mechanism by which the effect of insulin on lipid metabolism could be regulated independently of some of its other functions during development and adulthood. We speculate that this mechanism could be important in explaining the well-established link between obesity and insulin resistance that is observed in Type 2 diabetes.
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PMID:Cytoplasmic activated protein kinase Akt regulates lipid-droplet accumulation in Drosophila nurse cells. 1707 71

Prp19p is an integral component of the heteromeric protein complex (the NineTeen complex) in the nucleus, and it is essential for the structural integrity of NineTeen complex and its subsequent activation of the spliceosome. We identified Prp19p, which has never been reported in relation to any function outside of the nucleus, as a member of proteins associated with lipid droplets. Down-regulation of Prp19p expression with RNA interference in 3T3-L1 cells repressed lipid droplet formation with the reduction in the level of expression of perilipin and S3-12. The levels of expression of SCD1 (stearoyl-CoA desaturase-1), DGAT-1 (acyl-CoA diacylglycerol acyltransferase-1), and glycerol-3-phosphate acyltransferase were also reduced in Prp19p down-regulated cells, and a significant decrease in triglycerides was observed. Unlike perilipin, which is one of the most extensively studied lipid droplet-associated proteins, Prp19p is not essential for cAMP- and hormone-sensitive lipase-dependent lipolysis pathways, even though Prp19p is a component of the lipid droplet phospholipid monolayer, and down-regulation of Prp19p represses fat accretion significantly. These results suggest that Prp19p or Prp19-interacting proteins during lipid droplet biogenesis in adipocytes may be considered as another class of potential targets for attacking obesity and obesity-related problems.
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PMID:Identification of mouse Prp19p as a lipid droplet-associated protein and its possible involvement in the biogenesis of lipid droplets. 1711 36


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