Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects, is beneficial for various cardiac disorders. However, FGF21's role in heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we show that elevated circulating FGF21 levels are negatively associated with cardiac diastolic function in patients with HFpEF. Global or adipose FGF21 deficiency exacerbates cardiac diastolic dysfunction and damage in high-fat diet (HFD) plus N[w]-nitro-L-arginine methyl ester (L-NAME)-induced HFpEF mice, whereas these effects are notably reversed by FGF21 replenishment. Mechanistically, FGF21 enhances the production of adiponectin (APN), which in turn indirectly acts on cardiomyocytes, or FGF21 directly targets cardiomyocytes, to negatively regulate pyruvate dehydrogenase kinase 4 (PDK4) production by activating PI3K/AKT signals, then promoting mitochondrial bioenergetics. Additionally, APN deletion strikingly abrogates FGF21's protective effects against HFpEF, while genetic PDK4 inactivation markedly mitigates HFpEF in mice. Thus, FGF21 protects against HFpEF via fine-tuning the multiorgan crosstalk among the adipose, liver, and heart.
- MeSH
- adiponektin * metabolismus genetika MeSH
- dieta s vysokým obsahem tuků * škodlivé účinky MeSH
- energetický metabolismus * účinky léků MeSH
- fibroblastové růstové faktory * metabolismus genetika MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- kardiomyocyty * metabolismus účinky léků MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- PDH-kinasa * metabolismus genetika MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- signální transdukce MeSH
- srdeční mitochondrie * metabolismus účinky léků MeSH
- srdeční selhání * metabolismus prevence a kontrola genetika MeSH
- tepový objem účinky léků MeSH
- tuková tkáň metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Metabolic syndrome is a significant pro-inflammatory and pro-coagulant condition. The clinical association of adiponectin, a mainly antidiabetogenic molecule, and its interaction with platelets and platelet indices remains insufficiently investigated. OBJECTIVE: The aim of our study was to investigate the association of adiponectin with platelets and platelet indices in patients with metabolic syndrome. METHODS: The investigation was conducted as a cross-sectional study involving 113 subjects: 63 patients with the diagnosis of metabolic syndrome, and 50 healthy controls - with clear inclusion and exclusion criteria. The group of patients with metabolic syndrome was divided into two subgroups according to the platelet/high-density lipoprotein (HDL) ratio. RESULTS: The subgroup with a higher platelet/HDL ratio was prediabetic. In the same subgroup of patients, a positive correlation between the adiponectin and mean platelet volume (MPV) was seen, while linear regression (95% CI) confirmed the association. CONCLUSION: Considering that MPV is the index that indicates average platelet volume and activity, we believe this association with adiponectin can represent a protective compensatory response in patients with metabolic syndrome and prediabetes. Our results provide a basis for a more precise selection of patients in whom the future therapeutic application of recombinant adiponectin would be most effective.
- MeSH
- adiponektin * krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom * krev MeSH
- průřezové studie MeSH
- střední objem trombocytu * MeSH
- studie případů a kontrol MeSH
- trombocyty metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.
- MeSH
- adiponektin metabolismus krev MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- folikuly stimulující hormon krev MeSH
- GABA metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- hypothalamus * metabolismus účinky léků patologie MeSH
- inzulinová rezistence MeSH
- krysa rodu rattus MeSH
- leptin krev metabolismus MeSH
- letrozol farmakologie MeSH
- luteinizační hormon krev MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar * MeSH
- pyroptóza * účinky léků MeSH
- syndrom polycystických ovarií * chemicky indukované metabolismus farmakoterapie patologie MeSH
- testosteron krev MeSH
- triglyceridy krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tukové tkanivo je dynamický metabolický orgán, ktorý zabezpečuje metabolickú homeostázu organizmu. Sekrécia adipocytokínov závisí od distribúcie tukového tkaniva, ako aj bunkového zloženia samotného tukového tkaniva – dôležitý je podiel adipocytov, stromálnych buniek, ciev a buniek imunitného systému. Cieľom našich prác, ktoré dokumentuje tento článok, je zistiť vplyv vybraných adipocytokínov na metabolické a imunologické komplikácie po transplantácii obličky. V našich analýzach sme nepotvrdili vplyv chronickej imunosupresie na hladiny adiponektínu a leptínu. Zistili sme však, že vyššie hladiny leptínu predikovali vývoj potransplantačného diabetes mellitus a nízke hladiny adiponektínu boli spojené s obezitou. Taktiež sme potvrdili, že hyperleptinemia je spojená s rozvojom akútnej rejekcie štepu a tvorbou donor špecifických protilátok.
Adipose tissue is a dynamic metabolic organ that regulates the metabolic homeostasis of the body. The secretion of adipocytokines depends on the distribution of adipose tissue, as well as the cellular composition of the adipose tissue itself - the proportion of adipocytes, stromal cells, blood vessels and cells of the immune system is important. In our analyses, the effect of chronic immunosuppression on adiponectin and leptin levels has not been confirmed. However, we found that higher leptin levels predicted the development of post-transplant diabetes mellitus and low adiponectin levels were associated with obesity and insulin resistance. It was also confirmed that hyperleptinemia is associated with the development of acute graft rejection and the formation of donor specific antibodies.
- MeSH
- adiponektin škodlivé účinky MeSH
- leptin škodlivé účinky MeSH
- lidé MeSH
- rejekce štěpu etiologie MeSH
- rizikové faktory MeSH
- transplantace ledvin * MeSH
- tukové buňky * imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
- MeSH
- adipokiny * krev MeSH
- adiponektin krev nedostatek MeSH
- biologické markery krev MeSH
- dítě MeSH
- DNA vazebné proteiny krev MeSH
- idiopatické střevní záněty krev komplikace MeSH
- lidé MeSH
- mladiství MeSH
- nedostatek vitaminu D * komplikace krev MeSH
- nukleobindiny krev MeSH
- plazmatické proteiny vázající retinol metabolismus analýza MeSH
- proteiny vázající mastné kyseliny krev MeSH
- proteiny vázající vápník krev MeSH
- resistin krev MeSH
- studie případů a kontrol MeSH
- vitamin D * krev analogy a deriváty MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: C-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome. METHODS: Transgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers. RESULTS: The presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress. CONCLUSIONS: Our findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.
- MeSH
- adiponektin MeSH
- aorta MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- chemokin CCL2 MeSH
- hypertenze * MeSH
- inzuliny * metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- metabolický syndrom * diagnóza genetika MeSH
- oxidační stres MeSH
- potkani inbrední SHR MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Bariatric procedures are considered to be the most effective treatment options for obesity. One of them is laparoscopic sleeve gastrectomy (LSG), which is nowadays very popular and widely used. LSG leads to weight loss and metabolic improvement and also changes adipokine levels, although it is just a restrictive operation. We describe changes in pro-inflammatory (leptin, resistin, visfatin and chemerin) and anti-inflammatory adipokines (adiponectin, omentin), with adiponectin and leptin being most studied. Their levels are markedly changed after LSG and this may partially explain the weight loss seen after LSG. Adipokines are closely connected to insulin resistance and chronic inflammation both being positively influenced after LSG. Leptin regulates amount of body fat, appetite, thermogenesis and metabolic rate and its levels are positively correlated with both weight and BMI changes after operation. Resistin influences insulin sensitivity, modulates body cholesterol trafficking and its changes after operation correlate with BMI, waist circumference, fat mass, LDL cholesterol and C-reactive protein. Chemerin, an important component of immune system, decreases after bariatric surgery and its levels correlate with BMI, triglyceride levels, and blood glucose. On the other hand, pro-inflammatory adipokine adiponectin, which influences fatty acid oxidation, browning of fat tissue and energy metabolism, is declining after LSG. This decline explains improvement of glucose status after bariatric surgery in patients with diabetes and is correlated with BMI loss, waist circumference and LDL cholesterol level. Effect of LSG goes beyond calory restriction and the changes of adipokines have a great impact on health status of the bariatric patients.
- MeSH
- adipokiny MeSH
- adiponektin MeSH
- gastrektomie metody MeSH
- hmotnostní úbytek fyziologie MeSH
- inzulinová rezistence * fyziologie MeSH
- laparoskopie * metody MeSH
- LDL-cholesterol MeSH
- leptin MeSH
- lidé MeSH
- morbidní obezita * metabolismus chirurgie MeSH
- resistin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Background and objectives: Atherosclerosis is the underlying pathology of ischemic heart disease. There are many aggravating metabolic and oxidant parameters which are participating together overwhelming the pathology of vascular stenosis. Adipokines play a positive metabolic effect in healthy individuals and oxidation reaction greatly impacts the lipid metabolism and might negatively impact the condition. In the present study, we aimed to characterize the level of adiponectin, obestatin, and redox parameters in atherosclerotic patients.Methods: Serum was collected from atherosclerotic patients and froze to be ready for analysis.Results: The results indicated that hyperlipidemia significantly reduced adiponectin, obestatin, and antioxidant enzymes (catalase, glutathione, glutathione-S-transferase, and glutathione peroxidase) together with a significant increase in oxidant byproduct (malondialdehyde) and modulated lipid parameters (cholesterol, triglyceride, and high-density lipoprotein).Conclusion: The study concluded that atherosclerosis is associated with reduced antioxidant enzymes, obestatin, and adiponectin levels and increased lipid levels. These parameters play a great role in the patho-logical status of coronary stenosis.
- MeSH
- adiponektin krev metabolismus MeSH
- antioxidancia analýza metabolismus MeSH
- ateroskleróza etiologie patofyziologie MeSH
- ELISA MeSH
- ghrelin krev metabolismus MeSH
- hyperlipidemie * diagnóza etiologie patofyziologie MeSH
- koronární stenóza patofyziologie MeSH
- lidé MeSH
- malondialdehyd krev metabolismus MeSH
- metabolismus lipidů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinická studie MeSH
BACKGROUND: The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico. METHODS: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity. CONCLUSIONS: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.
- MeSH
- adiponektin genetika MeSH
- cholesterol MeSH
- jednonukleotidový polymorfismus * genetika MeSH
- lidé MeSH
- metabolické nemoci * MeSH
- mladiství MeSH
- nadváha epidemiologie genetika MeSH
- obezita epidemiologie genetika MeSH
- průřezové studie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Mexiko MeSH
Introduction: Monounsaturated fatty acids (MUFA) are understood to have therapeutic and preventive effects on chronic complications associated with type 2 diabetes mellitus (T2DM); however, there are differences between individual MUFAs. Although the effects of palmitoleic acid (POA) are still debated, POA can regulate glucose homeostasis, lipid metabolism, and cytokine production, thus improving metabolic disorders. In this study, we investigated and compared the metabolic effects of POA and oleic acid (OA) supplementation on glucose and lipid metabolism, insulin sensitivity, and inflammation in a prediabetic model, the hereditary hypertriglyceridemic rat (HHTg). HHTg rats exhibiting genetically determined hypertriglyceridemia, insulin resistance, and impaired glucose tolerance were fed a standard diet. POA and OA were each administered intragastrically at a dose of 100 mg/kg b.wt. for four weeks. Results: Supplementation with both MUFAs significantly elevated insulin and glucagon levels, but only POA decreased nonfasting glucose. POA-treated rats showed elevated circulating NEFA associated with increased lipolysis, lipoprotein lipase gene expression, and fatty acid reesterification in visceral adipose tissue (VAT). The mechanism of improved insulin sensitivity of peripheral tissues (measured as insulin-stimulated lipogenesis and glycogenesis) in POA-treated HHTg rats could contribute increased circulating adiponectin and omentin levels together with elevated FADS1 gene expression in VAT. POA-supplemented rats exhibited markedly decreased proinflammatory cytokine production by VAT, which can alleviate chronic inflammation. OA-supplemented rats exhibited decreased arachidonic acid (AA) profiles and decreased proinflammatory AA-derived metabolites (20-HETE) in membrane phospholipids of peripheral tissues. Slightly increased FADS1 gene expression after OA along with increased adiponectin production by VAT was reflected in slightly ameliorated adipose tissue insulin sensitivity (increased insulin-stimulated lipogenesis). Conclusions: Our results show that POA served as a lipokine, ameliorating insulin sensitivity in peripheral tissue and markedly modulating the metabolic activity of VAT including cytokine secretion. OA had a beneficial effect on lipid metabolism and improved inflammation by modulating AA metabolism.
- MeSH
- adiponektin MeSH
- antiflogistika MeSH
- cytokiny MeSH
- diabetes mellitus 2. typu * MeSH
- glukagon MeSH
- glukosa metabolismus MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence * MeSH
- krysa rodu rattus MeSH
- kyselina olejová farmakologie MeSH
- kyseliny arachidonové MeSH
- kyseliny mastné mononenasycené farmakologie terapeutické užití MeSH
- kyseliny mastné neesterifikované MeSH
- lipoproteinlipasa MeSH
- mastné kyseliny metabolismus MeSH
- prediabetes * farmakoterapie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH