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1.
A Distinctive NAFLD Signature in Adipose Tissue from Women with Severe Obesity.
Osorio-Conles, Ó, Vega-Beyhart, A, Ibarzabal, A, Balibrea, JM, Graupera, I, Rimola, J, Vidal, J, de Hollanda, A
International journal of molecular sciences. 2021;(19)
Abstract
Development and severity of nonalcoholic fatty liver disease (NAFLD) have been linked to obesity and white adipose tissue (WAT) dysfunction plays a key role in this relation. We compared the main features of subcutaneous (SAT) and visceral WAT (VAT) tissue dysfunction in 48 obese women without (Ob) and with NAFLD (Ob-NAFLD) undergoing bariatric surgery and matched for age, BMI and T2D status. Fat cell area, adipocyte size distribution, the degree of histological fibrosis and the mRNA expression of adipokines and genes implicated in inflammation, adipogenesis, angiogenesis, metabolism and extracellular matrix remodeling were measured by RT-qPCR in both fat depots. Ob-NAFLD group showed higher TG and lower HDL circulating levels, increased VAT fat cell area and similar WAT fibrosis in comparison with Ob group. A sPLS-DA was performed in order to identify the set of genes that better characterize the presence of NAFLD. Finally, we build a multinomial logistic model including seven genes that explained 100% of the variance in NAFLD and correctly predicted 100% of cases. Our data support the existence of distinctive NAFLD signatures in WAT from women with severe obesity. A better understanding of these pathways may help in future strategies for the prevention and treatment of NAFLD.
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Changes in Circulating Cytokines and Adipokines After RYGB in Patients with and without Type 2 Diabetes.
Katsogiannos, P, Kamble, PG, Pereira, MJ, Sundbom, M, Carlsson, PO, Eriksson, JW, Espes, D
Obesity (Silver Spring, Md.). 2021;(3):535-542
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Abstract
OBJECTIVE This study aimed to compare cytokine and adipokine levels in patients with obesity with and without type 2 diabetes (T2D) at baseline and 6 months after Roux-en-Y gastric bypass (RYGB) with healthy controls. METHODS A total of 34 patients (21 with T2D) with BMI of 30 to 45 kg/m2 were compared with 25 healthy controls without obesity. Cytokines, adipokines, and peptides of relevance for inflammation and metabolism were analyzed in plasma. RESULTS Significant decreases in weight and glycated hemoglobin A1c were observed. At baseline, interleukin-6 (IL-6), IFN-β, IL-18, leptin, and hepatocyte growth factor were higher in all patients with obesity compared with healthy controls. In patients without T2D, TNF-α, IL-1α, IL-2, IL-15, and visfatin were also increased, whereas bone morphogenic protein-4 was decreased. Following RYGB, IL-6 and hepatocyte growth factor were still increased in both groups compared with controls. In T2D patients, IFN-β, IL-27, IL-1α, IL-2, regenerating islet-derived protein 3A, visfatin, and osteopontin were found to be increased. In patients without T2D, TNF-α, IL-1α, IL-2, IL-15, leptin, and visfatin remained increased. CONCLUSIONS The altered cytokine profile of patients with obesity persisted after RYGB despite large weight loss and improved metabolic status, thus reflecting an inherent inflammatory state.
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The Metabolic Syndrome: Emerging Novel Insights Regarding the Relationship between the Homeostasis Model Assessment of Insulin Resistance and other Key Predictive Markers in Young Adults of Western Algeria.
Belhayara, MI, Mellouk, Z, Hamdaoui, MS, Bachaoui, M, Kheroua, O, Malaisse, WJ
Nutrients. 2020;(3)
Abstract
Several biological markers have been identified as risk factors for cardiovascular disease and are associated with increased risk of metabolic syndrome (MetS). This study provides a factual information on promising biomarkers that are associated with MetS and can aid in early detection and management of MetS in young adults of Western Algeria. We studied a total of one hundred subjects aged between thirty and forty years with MetS, in which anthropometric measurements, insulin resistance, C peptide and HbA1c, lipid profile, circulating adipokines and glucagon-like peptide-1 were measured by suitable methods, in comparison to two groups of control. MetS is closely linked to altered glucose homeostasis, the plasma insulin/glucose ratio; i.e., the insulinogenic index helps to estimate the level of insulin secretion and also for assessing β-cell function. The correlation between homeostasis model assessment insulin resistance index (HOMA-IR) and HbA1c, body mass index or plasma triglycerides yielded positive and significant values. Biomarkers with a known and predictable association with MetS can provide a means to detect those at risk and intervene as needed. This could significantly decrease the burden complications impose on patients and the healthcare system.
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Plasma Adipokines in Patients Resuscitated from Cardiac Arrest: Difference of Visfatin between Survivors and Nonsurvivors.
Chen, YZ, Zhou, SQ, Chen, YQ, Peng, H, Zhuang, YG
Disease markers. 2020;:9608276
Abstract
BACKGROUND Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). METHODS Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. RESULTS The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (P < 0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (P < 0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. CONCLUSION Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC.
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Effects of preoperative oral carbohydrate intake on catabolism, nutrition and adipocytokines during minor surgery: A randomized, prospective, controlled clinical phase II trial.
Morimoto, Y, Kinugawa, T, Hayashi, M, Iida, T, Yamamoto, T
PloS one. 2019;(5):e0216525
Abstract
BACKGROUND We investigated the effects of preoperative oral carbohydrate loading on intraoperative catabolism, nutritional parameters, and adipocytokine levels during anesthesia. METHODS Study participants were randomized to two groups who were allowed to consume either no more than 250 mL of 18% oral carbohydrate solution (Arginaid Water: AW group) or no more than 500 mL of plain water (PW group) within the 2 hours before surgery, with no intraoperative glucose administration. Percentage changes from preoperative values of resting metabolic rate (RMR) and total body water (TBW), determined by bioelectrical impedance analysis (BIA), were compared. Blood levels of serum ketone bodies, free fatty acids (FFAs), insulin, 3-methyl histidine, blood glucose, retinol binding protein, adiponectin, and leptin were measured. BIA measurement and blood sampling were performed on entry to the operating room (M1) and 2 hours after the induction of anesthesia (M2). Chi squared test, Mann-Whitney U test, and Wilcoxon's test were used for comparisons of parameters. P values less than 0.05 constituted a significant difference. RESULTS Seventeen patients per group (34 patients total) were enrolled. RMR and TBW values did not differ between M1 and M2 measurements. Participants in the AW group had lower blood ketone body and FFA levels and higher insulin levels at M1. However, their ketone body and FFA levels rose and insulin levels fell after 2 hours, although ketone body and FFA levels in the AW group were still lower than those in the PW group. Although retinol binding protein, adiponectin, and leptin levels were not different in terms of preoperative oral carbohydrate loading, the levels of these substances in both groups were lower after 2 hours compared with levels on operating room entry. CONCLUSIONS Preoperative oral carbohydrate loading without intraoperative glucose administration appears to suppress catabolism for 2 hours after the start of surgery.
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Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines.
Linossier, MT, Amirova, LE, Thomas, M, Normand, M, Bareille, MP, Gauquelin-Koch, G, Beck, A, Costes-Salon, MC, Bonneau, C, Gharib, C, et al
PloS one. 2017;(8):e0182970
Abstract
BACKGROUND Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones. METHODS Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h). Markers of bone turnover, phosphocalcic metabolism, adipokines and associated factors were measured. RESULTS Bone resorption as assessed by tartrate-resistant acid phosphatase isoform 5b and N-terminal crosslinked telopeptide of type I collagen levels increased as early as DI24h. At the same time, total procollagen type I N- and C-terminal propeptides and osteoprotegerin, representing bone formation markers, decreased. Total osteocalcin [OC] was unaffected, but its undercarboxylated form [Glu-OC] increased from DI24h to R+3h. The early and progressive increase in bone alkaline phosphatase activities suggested an increased mineralization. Dickkopf-1 and sclerostin, as negative regulators of the Wnt-β catenin pathway, were unaltered. No change was observed either in phosphocalcic homeostasis (calcium and phosphate serum levels, 25-hydroxyvitamin D, fibroblast growth factor 23 [FGF23]) or in inflammatory response. Adiponectemia was unchanged, whereas circulating leptin concentrations increased. Neutrophil gelatinase-associated lipocalin [lipocalin-2], a potential regulator of bone homeostasis, was found elevated by 16% at R+3h compared to DI24h. The secretory form of nicotinamide phosphoribosyl-transferase [visfatin] concentrations almost doubled after one day of DI and remained elevated. Serum insulin-like growth factor 1 levels progressively increased. Fasting insulin concentrations increased during the entire DI, whereas fasting glucose levels tended to be higher only at DI24h and then returned to BDC values. Changes in bone resorption parameters negatively correlated with changes in bone formation parameters. Percent changes of ultra-sensitive C-reactive protein positively correlated with changes in osteopontin, lipocalin-2 and fasting glucose. Furthermore, a positive correlation was found between changes in FGF23 and Glu-OC, the two main osteoblast-/osteocyte-derived hormones. CONCLUSION Our results demonstrated that DI induced an unbalanced remodeling activity and the onset of insulin resistance. This metabolic adaptation was concomitant with higher levels of Glu-OC. This finding confirms the role of bone as an endocrine organ in humans. Furthermore, visfatin for which a great responsiveness was observed could represent an early and sensitive marker of unloading in humans.
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Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study.
Tarpgaard, LS, Guren, TK, Glimelius, B, Christensen, IJ, Pfeiffer, P, Kure, EH, Sorbye, H, Ikdahl, T, Yilmaz, M, Johansen, JS, et al
PloS one. 2014;(2):e87746
Abstract
BACKGROUND We aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with first-line oxaliplatin and 5-flourouracil with or without cetuximab. PATIENTS AND METHODS A total of 566 patients in the NORDIC VII Study were randomized 1∶1∶1 to arm A (Nordic FLOX), arm B (Nordic FLOX + cetuximab), or arm C (Nordic FLOX + cetuximab for 16 weeks followed by cetuximab alone as maintenance therapy). Pretreatment plasma samples were available from 510 patients. Plasma YKL-40 was determined by ELISA and dichotomized according to the age-corrected 95% YKL-40 level in 3130 healthy subjects. RESULTS Pretreatment plasma YKL-40 was elevated in 204 patients (40%), and median YKL-40 was higher in patients with mCRC than in healthy subjects (age adjusted, P<0.001). Patients with elevated YKL-40 had shorter PFS than patients with normal YKL-40 (7.5 vs. 8.2 months; hazard ratio (HR) = 1.27 95% confidence interval (CI) 1.05-1.53 P = 0.013) and shorter OS (16.8 vs. 23.9 months; HR = 1.33, 1.04-1.69, P = 0.024). Multivariate Cox analysis demonstrated that elevated pretreatment YKL-40 was an independent biomarker of short OS (HR = 1.12, 1.01-1.25, P = 0.033). The ratio of the updated plasma YKL-40 (i.e. level after 1, 2, 8 weeks of treatment, and at end of treatment compared to the baseline level) was associated with OS (HR = 1.27, 1.06-1.52, P = 0.011). CONCLUSIONS Plasma YKL-40 is an independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy alone or combined with cetuximab.
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Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects.
Brøns, C, Jacobsen, S, Hiscock, N, White, A, Nilsson, E, Dunger, D, Astrup, A, Quistorff, B, Vaag, A
American journal of physiology. Endocrinology and metabolism. 2012;(1):E43-51
Abstract
Low birth weight (LBW) is associated with an increased risk of insulin resistance and downregulation of oxidative phosphorylation (OXPHOS) genes when exposed to a metabolic challenge of high-fat overfeeding (HFO). To elaborate further on the differential effects of HFO in LBW subjects, we measured in vivo mitochondrial function, insulin secretion, hepatic glucose production, and plasma levels of key regulatory hormones before and after 5 days of HFO in 20 young LBW and 26 normal-birth-weight (NBW) men. The LBW subjects developed peripheral insulin resistance after HFO due to impaired endogenous glucose storage (9.42 ± 4.19 vs. 5.91 ± 4.42 mg·kg FFM(-1)·min(-1), P = 0.01). Resting muscle phosphorcreatine and total ATP in muscle increased significantly after HFO in LBW subjects only, whereas additional measurements of mitochondrial function remained unaffected. Despite similar plasma FFA levels, LBW subjects displayed increased fat oxidation during insulin infusion compared with normal-birth-weight (NBW) subjects after HFO (0.37 ± 0.35 vs. 0.17 ± 0.33 mg·kg FFM(-1)·min(-1), P = 0.02). In contrast to NBW subjects, the plasma leptin levels of LBW subjects did not increase, and the plasma gastric inhibitory polypeptide (GIP) as well as pancreatic polypeptide (PP) levels increased less in LBW compared with NBW subjects during HFO. In conclusion, HFO unmasks dissociation between insulin resistance and mitochondrial dysfunction in LBW subjects, suggesting that insulin resistance may be a cause, rather than an effect, of impaired muscle OXPHOS gene expression and mitochondrial dysfunction. Reduced increments in response to HFO of fasting plasma leptin, PP, and GIP levels may contribute to insulin resistance, lower satiety, and impaired insulin secretion in LBW subjects.
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Supplementation of highly concentrated β-cryptoxanthin in a satsuma mandarin beverage improves adipocytokine profiles in obese Japanese women.
Iwamoto, M, Imai, K, Ohta, H, Shirouchi, B, Sato, M
Lipids in health and disease. 2012;:52
Abstract
BACKGROUND Serum β-cryptoxanthin levels are lower in overweight subjects than in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects have been reported. There are several reports that serum β-cryptoxanthin levels in them were relatively lower than normal subjects. OBJECTIVE We hypothesize that supplementation of highly concentrated β-cryptoxanthin improves serum adipocytokine profiles in obese subjects. This study tested the association between β-cryptoxanthin intake and serum adipocytokine levels. METHODS An intervention study consisted of a 3-week long before-and-after controlled trial, where β-cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women. RESULTS The results indicated no significant changes in body weight or body mass index (BMI). Serum β-cryptoxanthin levels increased significantly by 4-fold. Serum high molecular weight (HMW)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (PAI)-1 levels decreased. CONCLUSIONS We concluded that increasing the intake of β-cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.
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[Achetylcholinesterase (AChE) inhibition and serum lipokines in Alzheimer's disease: friend or foe?].
Kovacs, J, Pakaski, M, Juhasz, A, Feher, A, Drotos, G, Fazekas, CO, Horvath, TL, Janka, Z, Kalman, J
Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology. 2012;(1):19-27
Abstract
Throughout the natural progression of Alzheimer's disease (AD), the body mass index (BMI) decreases. This is believed to be brought on by the disturbance in the central lipid metabolism, but the exact mechanism is yet unknown. Adipokines (adiponectin, leptin), hormones produced by the adipose tissue, change glucose and lipid metabolism, and have an anorectic effect through increasing energy consumption in the hypothalamus. The goal of our study was to examine donepezil - an acetylcholinesterase inhibitor (AChEI) currently used in AD therapy -, and to what degree it influences the serum adipokine levels and metabolic parameters of AD patients. During the self-evaluation of 26 clinically diagnosed mild to moderate AD patients, therapy with 10 mg/day donepezil was started according to current protocols. We measured serum adiponectin, leptin, LDL, HDL, trigliceride levels, and BMI and ApoE polymorphism at the beginning of our study, and at 3 and 6-months intervals respectively. All data were analyzed with SPSS 17. In comparison with pre-donepezil therapy values, at the third month interval serum adiponectin levels showed an increasing and leptin levels a decreasing tendency. At the six month interval, adiponectin levels significantly increased (p=0.007), leptin levels decreased (p=0.013), BMI (p=0.001) and abdominal circumference (p=0.017) was significantly lower at 6 months as compared to control values. We did not observe any changes in the lipid profile, and ApoE4 allele carrying showed no association with the parameters. To our knowledge, we are the first to publish that AChEI therapy with donepezil alters lipokine levels, which positively influences the currently known pathomechanism and numerous risk factors of AD. The AChEI treatment-induced weight loss should be considered in the long-term therapy of AD patients.