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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of fetal programming on intermediary metabolism is uncertain. Therefore, we examined whether fetal programming affects oxidative and nonoxidative macronutrient metabolism and the prevalence of the metabolic syndrome in adult life. Healthy older men, aged 64-72 years, with either a lower birth weight (LBW, <or=25th %ile; n = 16) or higher birth weight (HBW, >or=75th %ile; n = 13) had measurements of 1) net oxidative metabolism using indirect calorimetry before and for 6 h after a mixed meal (3,720 kJ) and 2) postprandial oxidation of exogenous [13C]palmitic acid. Body composition was measured using dual-energy X-ray absorptiometry. After adjustment for current weight and height, the LBW group had a lower resting energy expenditure (REE) in the preprandial (4.01 vs. 4.54 kJ/min, P = 0.015) and postprandial state (4.60 vs. 5.20 kJ/min, P = 0.004), and less fat-free mass than the HBW group. The BW category was a significant, independent, and better predictor of REE than weight plus height. There were no significant differences between groups in net oxidative and nonoxidative macronutrient (protein, fat, carbohydrate) metabolism (or of exogenous [13C]palmitate) or in the prevalence of the metabolic syndrome, which was present almost twice as commonly in the LBW than in the HBW group. The study suggests that fetal programming affects both pre- and postprandial EE in older life by mechanisms that are at least partly related to the mass of the fat-free body. BW was found to be a significant predictor of REE that was independent of adult weight plus height.
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PMID:Substrate-energy metabolism and metabolic risk factors for cardiovascular disease in relation to fetal growth and adult body composition. 1653 6

In metabolic syndrome, a systemic deregulation of the insulin pathway leads to a combined deregulation of insulin-regulated metabolism and cardiovascular functions. Free fatty acids (FFAs), which are increased in metabolic syndrome, inhibit insulin signaling and induce metabolic insulin resistance. This study was designed to examine FFAs' effects on vascular insulin signaling and endothelial nitric oxide (NO) synthase (eNOS) activation in endothelial cells. We showed that FFAs inhibited insulin signaling and eNOS activation through different mechanisms. While linoleic acid inhibited Akt-mediated eNOS phosphorylation, palmitic acid appeared to affect the upstream signaling. Upregulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) activity and transcription by palmitic acid mediated the inhibitory effects on insulin signaling. We further found that activated stress signaling p38, but not Jun NH(2)-terminal kinase, was involved in PTEN upregulation. The p38 target transcriptional factor activating transcription factor (ATF)-2 bound to the PTEN promoter, which was increased by palmitic acid treatment. In summary, both palmitic acid and linoleic acid exert inhibitory effect on insulin signaling and eNOS activation in endothelial cells. Palmitic acid inhibits insulin signaling by promoting PTEN activity and its transcription through p38 and its downstream transcription factor ATF-2. Our findings suggest that FFA-mediated inhibition of vascular insulin signaling and eNOS activation may contribute to cardiovascular diseases in metabolic syndrome.
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PMID:Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase. 1687 94

Many factors are involved in infants' health; one of the most important of them may be the kind of early feeding. Recent evidences suggest that breastfeeding, in addition to its well-established beneficial effects during lactation period, provides also beneficial long-term effects, like the protection against infectious and immune-related diseases, a better cognitive development, a decreased risk of metabolic syndrome and of obesity. It has been reported that the early feeding mode affects growth and body composition and it could be considered a critical factor for metabolic development. Human milk is a source of different nutrients and bioactive factors, especially hormones and growth factors like leptin, ghrelin, insulin, insulin-like growth factor (IGF-I) playing a role in food intake regulation, metabolism and body composition. In particular breast milk leptin may provide a physiological explanation for a number of advantages seen in reaching proper growth and energy balance in breast-fed infants compared with formula fed ones. Etiopathogenesis and therapeutic approach in common minor gastrointestinal diseases in infants are important subject of study for pediatricians. Colic, constipation and regurgitation can be considered feeding problems and they might benefit from dietary treatment. Regarding infantile colic, dietary modifications seem to be more suitable than pharmacological treatment in resolving symptoms; also prebiotics and probiotics are useful for this aim. The occurence of constipation is related to the kind of feeding and it is lower in breastfed infants. Moreover formulas with probiotics and beta-palmitic acid could promote a regression of symptoms. A dietary approach may be useful also in regurgitation. Anyway we have to remember that breastfeeding require a supplementation of vitamin D and K for some months and a correct weaning program is needed from the 5th-6th months of life to prevent iron deficiency.
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PMID:[Breast milk: biological constituents for health and well-being in infancy]. 1726 42

Palmitate is the most abundant saturated fatty acid in the human diet and the major one synthesized de novo. To identify palmitate-regulated genes we performed whole genome mRNA expression profiling by using human hepatoma HepG2 cells. We identified eleven genes which are significantly (single-sided permutational t-test, p<0.05) regulated by low concentration of palmitate (50 microM). We observed a decreased expression of five metallothioneins, and an increased expression of liver expressed plasminogen activator inhibitor-1 protein and insulin-like growth factor II, which play a prominent role in the development of the metabolic syndrome. Comparative promoter analysis in-silico revealed common transcriptional regulation of differentially expressed genes through erythroid kruppel-like factor and members of the zinc binding protein factor family. In conclusion, low physiological palmitate concentrations changed expression of very responsive genes.
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PMID:Identification of palmitate-regulated genes in HepG2 cells by applying microarray analysis. 1765 92

Channels formed by the gap junction protein connexin36 (Cx36) contribute to the proper control of insulin secretion. We investigated the impact of chronic hyperlipidemia on Cx36 expression in pancreatic beta-cells. Prolonged exposure to the saturated free fatty acid palmitate reduced the expression of Cx36 in several insulin-secreting cell lines and isolated mouse islets. The effect of palmitate was fully blocked upon protein kinase A (PKA) inhibition by H89 and (Rp)-cAMP, indicating that the cAMP/PKA pathway is involved in the control of Cx36 expression. Palmitate treatment led to overexpression of the inducible cAMP early repressor (ICER-1gamma), which bound to a functional cAMP-response element located in the promoter of the CX36 gene. Inhibition of ICER-1gamma overexpression prevented the Cx36 decrease, as well as the palmitate-induced beta-cell secretory dysfunction. Finally, freshly isolated islets from mice undergoing a long term high fat diet expressed reduced Cx36 levels and increased ICER-1gamma levels. Taken together, these data demonstrate that chronic exposure to palmitate inhibits the Cx36 expression through PKA-mediated ICER-1gamma overexpression. This Cx36 down-regulation may contribute to the reduced glucose sensitivity and altered insulin secretion observed during the pre-diabetic stage and in the metabolic syndrome.
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PMID:ICER-1gamma overexpression drives palmitate-mediated connexin36 down-regulation in insulin-secreting cells. 1807 14

The ATP-binding cassette transporters ABCA1 and ABCG1 are highly expressed in macrophage-derived foam cells and promote reverse cholesterol efflux via biogenesis of high-density lipoproteins. The aim of this study was to analyze the direct effects of bioactive factors related to the metabolic syndrome on macrophage transcript levels of all 47 human ABC transporters. Using in vitro M-CSF predifferentiated macrophages and TaqMan low density arrays we could show that linoleic acid, palmitic acid, and high glucose levels have a major impact on ABCA1 and ABCG1 expression but do not strongly affect most other human ABC transporters. In Western blot experiments we demonstrate that ABCA1 and ABCG1 protein levels are synchronously suppressed by high glucose levels and the w6-unsaturated fatty acid linoleic acid. We conclude that metabolites associated with the metabolic syndrome enhance the formation of atherosclerotic lesions by diminishing the reverse cholesterol transport function of ABCA1 and ABCG1.
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PMID:High glucose, unsaturated and saturated fatty acids differentially regulate expression of ATP-binding cassette transporters ABCA1 and ABCG1 in human macrophages. 1928 93

Inflammation and insulin resistance associated with visceral obesity are important risk factors for the development of type 2 diabetes, atherosclerosis, and the metabolic syndrome. The 12/15-lipoxygenase (12/15-LO) enzyme has been linked to inflammatory changes in blood vessels that precede the development of atherosclerosis. The expression and role of 12/15-LO in adipocytes have not been evaluated. We found that 12/15-LO mRNA was dramatically upregulated in white epididymal adipocytes of high-fat fed mice. 12/15-LO was poorly expressed in 3T3-L1 fibroblasts and was upregulated during differentiation into adipocytes. Interestingly, the saturated fatty acid palmitate, a major component of high fat diets, augmented expression of 12/15-LO in vitro. When 3T3-L1 adipocytes were treated with the 12/15-LO products, 12-hydroxyeicosatetranoic acid (12(S)-HETE) and 12-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), expression of proinflammatory cytokine genes, including tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and IL-12p40, was upregulated whereas anti-inflammatory adiponectin gene expression was downregulated. 12/15-LO products also augmented c-Jun N-terminal kinase 1 (JNK-1) phosphorylation, a known negative regulator of insulin signaling. Consistent with impaired insulin signaling, we found that insulin-stimulated 3T3-L1 adipocytes exhibited decreased IRS-1(Tyr) phosphorylation, increased IRS-1(Ser) phosphorylation, and impaired Akt phosphorylation when treated with 12/15-LO product. Taken together, our data suggest that 12/15-LO products create a proinflammatory state and impair insulin signaling in 3T3-L1 adipocytes. Because 12/15-LO expression is upregulated in visceral adipocytes by high-fat feeding in vivo and also by addition of palmitic acid in vitro, we propose that 12/15-LO plays a role in promoting inflammation and insulin resistance associated with obesity.
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PMID:12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. 1952 44

Serum fatty acids (FAs) have wide effects on metabolism: Serum saturated fatty acids (SFAs) increase triglyceride (TG) levels in plasma, whereas polyunsaturated fatty acids (PUFAs) reduce them. Traditionally, Eskimos have a high consumption of omega-3 fatty acids (omega3 FAs); but the Westernization of their food habits has increased their dietary SFAs, partly reflected in their serum concentrations. We studied the joint effect of serum SFAs and PUFAs on circulating levels of TGs in the presence of metabolic syndrome components. We included 212 men and 240 women (age, 47.9 +/- 15.7 years; body mass index [BMI], 26.9 +/- 5.3) from 4 villages located in Alaska for a cross-sectional study. Generalized linear models were used to build surface responses of TG as functions of SFAs and PUFAs measured in blood samples adjusting by sex, BMI, and village. The effects of individual FAs were assessed by multiple linear regression analysis, and partial correlations (r) were calculated. The most important predictors for TG levels were glucose tolerance (r = 0.116, P = .018) and BMI (r = 0.42, P < .001). Triglyceride concentration showed negative associations with 20:3omega6 (r = -0.16, P = .001), 20:4omega6 (r = -0.14, P = .005), 20:5omega3 (r = -0.17, P < .001), and 22:5omega3 (r = -0.26, P < .001), and positive associations with palmitic acid (r = 0.16, P < .001) and 18:3omega3 (r = 0.15, P < .001). The surface response analysis suggested that the effect of palmitic acid on TG is blunted in different degrees according to the PUFA chemical structure. The long-chain omega3, even in the presence of high levels of saturated fat, was associated with lower TG levels. Eicosapentaenoic acid (20:5omega3) had the strongest effect against palmitic acid on TG. The total FA showed moderate association with levels of TG, whereas SFA was positively associated and large-chain PUFA was negatively associated. The Westernized dietary habits among Eskimos are likely to change their metabolic profile and increase comorbidities related to metabolic disease.
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PMID:Polyunsaturated fatty acids effect on serum triglycerides concentration in the presence of metabolic syndrome components. The Alaska-Siberia Project. 1976 68

Increasing evidence suggests that elevation of plasma fatty acids that often accompanies insulin resistance contributes to beta-cell insufficiency in obesity-related type 2 diabetes. Circulating levels of hepatocyte growth factor (HGF) are increased in humans with metabolic syndrome and obesity. HGF is known to protect beta-cells against streptozotocin and during islet engraftment. However, whether HGF is a beta-cell prosurvival factor in situations of excessive lipid supply has not been deciphered. Mice overexpressing HGF in the beta-cell [rat insulin type II promoter (RIP)-HGF transgenic mice] fed with standard chow display improved glucose homeostasis and increased beta-cell mass and proliferation compared with normal littermates. However, after 15 wk of high-fat feeding, glucose homeostasis and beta-cell expansion and proliferation are indistinguishable between normal and transgenic mice. Interestingly, RIP-HGF transgenic mouse beta-cells and normal beta-cells treated with HGF display increased sensitivity to palmitate-mediated apoptosis in vitro. Palmitate completely eliminates Akt and Bad phosphorylation in RIP-HGF transgenic mouse islets. HGF-overexpressing islets also show significantly decreased AMP-activated protein kinase-alpha and acetyl-coenzyme A carboxylase phosphorylation, diminished fatty acid oxidation, increased serine palmitoyltransferase expression, and enhanced ceramide formation compared with normal islets. Importantly, human islets overexpressing HGF also display increased beta-cell apoptosis in the presence of palmitate. Treatment of both mouse and human islet cells with the de novo ceramide synthesis inhibitors myriocin and fumonisin B1 abrogates beta-cell apoptosis induced by HGF and palmitate. Collectively, these studies indicate that HGF can be detrimental for beta-cell survival in an environment with excessive fatty acid supply.
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PMID:Novel proapoptotic effect of hepatocyte growth factor: synergy with palmitate to cause pancreatic {beta}-cell apoptosis. 2017 23

The article presents results of the study of fatty-acid spectrum of triglycerides in insulin resistance patients with metabolic syndrome. An analysis was done on fatty-acid spectrum of triglycerides in healthy men and women, difference between types of dislipidemia diagnosed in men and women, including women in regard to their reproductive function. The authors found increase in palmitic acid level in fatty-acid spectrum of triglycerides in patients with diabetes mellitus type 2. Conclusion was made on correction of patient diet at the expense of ratio of saturated, nonsaturated and essential polyene acids: decrease in quantity of palmitic acid and increase in oleic acid for primary and secondary prevention atherosclerosis.
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PMID:[Features of fatty-acid spectrum of triglycerides in patients with insulin resistance and metabolic syndrome]. 2045 48


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