European Journal of Nutrition (v.51, #5)

The role of adipokines in connective tissue diseases by Robert Krysiak; Gabriela Handzlik-Orlik; Boguslaw Okopien (513-528).
To discuss the relationship between adipokines and connective tissue diseases, by putting special emphasis on the potential role of leptin, adiponectin, resistin, and other adipose tissue products in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus and on possible application of adipokine-targeted therapy in the treatment of these disorders with emphasis on the recent findings.PubMed literature search complemented by review of bibliographies listed in identified articles.Most of the data presented by different research groups showed changed levels of leptin, adiponectin, and resistin and occasionally also other adpokines in rheumatoid arthritis and systemic lupus erythematosus. The relationship between the remaining connective tissue diseases and adipokines is less documented.Plasma levels of adipokines might tell us too little about their role in connective tissue disorders, whereas adipokine effects on synovial tissues might differ from their known metabolic or cardiovascular effects, which implies that some re-appraisal of adipokines role may need to take place. It still remains obscure whether the observed disturbances in various adipokine systems in subjects with connective tissue diseases contribute to their development or only reflect the presence or activity of inflammatory process, which itself is induced by other pro-inflammatory factors.
Keywords: Adipose tissue; Adiponectin; Leptin; Resistin; Rheumatoid arthritis; Systemic lupus erythematosus

Platyconic acid, a saponin from Platycodi radix, improves glucose homeostasis by enhancing insulin sensitivity in vitro and in vivo by Dae Young Kwon; Young Seob Kim; Shi Yong Ryu; Yeon Hee Choi; Mi-Ran Cha; Hye Jeong Yang; Sunmin Park (529-540).
Previous research demonstrated that the crude saponins of Platycodi radix improve glucose metabolism by enhancing insulin sensitivity in type 2 diabetic animals; however, which individual saponins are the most potent insulin sensitizers is unknown.This study investigated which saponin(s) have anti-diabetic action in vitro and in vivo.The insulin-stimulated glucose uptake and PPAR-γ agonistic actions of six saponins from Platycodi radix were investigated in 3T3-L1 adipocytes, and glucose-stimulated insulin secretion was determined in Min6 cells. Four individual saponins (20 mg/kg body weight) were orally administered to low-dose streptozotocin-injected diabetic mice fed a high-fat diet for 8 weeks to evaluate glucose tolerance by oral glucose tolerance testing (OGTT), insulin sensitivity by insulin tolerance testing, and insulin signaling in the liver and adipose tissues.Platyconic acid (PA) most effectively increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes, possibly in part by working as a peroxisome proliferator-activated receptors (PPAR)-γ activator; however, none of the saponins improved glucose-stimulated insulin secretion in insulinoma cells. PA-treated diabetic mice exhibited the lowest peak serum glucose levels and highest serum insulin levels during the first part of OGTT. PA also improved insulin sensitivity: PA increased glycogen accumulation and decreased triacylglycerol storage in liver, which was associated with enhanced hepatic insulin signaling, while PA potentiated the expression of adiponectin and PPAR-γ in adipose tissue, and improved insulin signaling and increased GLUT4 translocation into the membranes.PA improves glucose homeostasis in type 2 diabetic mice, partly by enhancing hepatic and adipocyte insulin sensitivity, possibly by activating PPAR-γ.
Keywords: Platyconic acid; Platycodine D; Platycodi radix; PPAR-γ; Liver

Four-week ingestion of blood orange juice results in measurable anthocyanin urinary levels but does not affect cellular markers related to cardiovascular risk: a randomized cross-over study in healthy volunteers by Lucia Giordano; Walter Coletta; Chiara Tamburrelli; Marco D’Imperio; Marilena Crescente; Cristian Silvestri; Paolo Rapisarda; Giuseppe Reforgiato Recupero; Amalia De Curtis; Licia Iacoviello; Giovanni de Gaetano; Domenico Rotilio; Chiara Cerletti; Maria Benedetta Donati (541-548).
Blood orange juice (OJ) is an important source of anthocyanins (ACN). The latter molecules are endowed with antioxidant activity and might thus modulate different cell function. Our aim was to investigate ACN absorption following a 1-month daily supplementation of blood OJ and their potential effects on cell markers of platelet and leukocyte activation and interaction.Eighteen healthy subjects (10 men and 8 women) were supplemented for 4 weeks with 1 L/day of either blood OJ or blond OJ (that contains no ACN), following a cross-over design. Blood samples were obtained from fasting participants both at baseline and after each week of treatment to measure plasma ACN concentration. At the same time-intervals, 24-h urinary excretion of these molecules was also measured. At the beginning and the end of each 4-week intervention period, platelet and leukocyte markers and mixed cell conjugates were assessed both in basal condition and upon in vitro collagen/ADP activation.After 1 week supplementation with blood OJ, 24-h urinary excretion of ACN reached average levels of 11.47 ± 5.63 nmol that significantly differed from baseline and remained substantially unchanged until the end of treatment. No plasma accumulation of ACN following blood OJ supplementation was observed. Cellular markers were not significantly affected by either OJ after 4-week supplementation.Following supplementation of healthy volunteers with 1 L/day of blood OJ for 4 weeks, the ACN plasma levels reached were insufficient to significantly modify cell markers of platelet and leukocyte activation and interaction.
Keywords: Blood orange juice; Anthocyanins; Bioavailability; Platelets; Leukocytes

Short-term supplementation with Aronia melanocarpa extract improves platelet aggregation, clotting, and fibrinolysis in patients with metabolic syndrome by Joanna Sikora; Marlena Broncel; Magdalena Markowicz; Maciej Chałubiński; Katarzyna Wojdan; Elżbieta Mikiciuk-Olasik (549-556).
A diet rich in berries is believed to play a distinct role in the prevention of metabolic diseases associated with obesity. So far, there have been no published clinical observations evaluating the influence of Aronia melanocarpa on hemostasis. The aim of our study was to investigate the effects of A. melanocarpa extract (AM) supplementation on platelet aggregation, clot formation, and lysis in patients with metabolic syndrome (MS).Middle-aged non-medicated subjects with MS (n = 38) and 14 healthy volunteers were included in this study. Patients with MS were treated with 100 mg of AM three times daily for 2 months.We observed a significant reduction in the concentration of TC, LDL-C, and TG after AM supplementation. Beneficial changes in coagulation parameters were also observed. After 1 month of AM administration, we noticed significant inhibition of platelet aggregation. However, this effect became less pronounced after 2 months of supplementation. In the case of coagulation induced by endogenic thrombin, a significant decrease in the overall potential for coagulation was induced after 1 or 2 months of supplementation. Moreover, after 1 month of AM extract supplementation, we observed a beneficial reduction in the overall potential for clot formation and fibrinolysis.We observed the normalization of hemostasis parameters in MS patients after both 1 and 2 months of AM administration. After 1 month of AM supplementation, we found favorable changes in regards to the overall potential for plasma clotting, clot formation, and lysis, as well as in the lipid profiles of subjects.
Keywords: Aronia; Coagulation; Fibrinolysis; Metabolic syndrome; Platelet aggregation

Excessive iodine intake in schoolchildren by Adriana Lelis Carvalho; Clarissa Janson Costa de Souza Meirelles; Luciana Abrão Oliveira; Telma Maria Braga Costa; Anderson Marliere Navarro (557-562).
Inadequate iodine intake may result in iodine deficiency disorders (IDD). Thus, for more than 50 years, policies for the regulation of salt fortification with iodine have existed in Brazil. In 2003, a study on 6–14-year-old schoolchildren from regions of the state of São Paulo showed a median urinary iodine concentration of 360 μg/L. The objective of the present study was to assess the iodine nutrition status among schoolchildren.The study was conducted on 828 schoolchildren aged 4–13 years from eight schools in the interior of the state of São Paulo. A casual urine sample was collected from each volunteer for iodine determination by the adapted method of Sandell-Kalthoff.Only 1.9% (n = 16) of the children evaluated had low values of urinary iodine (<100 μg/L), while 24.6% had urinary iodine excretion values between 200 and 300 μg/L, and 67.1% had values above >300 μg/L.The results show that the iodine nutritional status of the schoolchildren studied is characterized by a high urinary iodine excretion, which might reveal an increase in iodine consumption by this population.
Keywords: Urinary iodine; Schoolchildren; Iodine; Salt

Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human aortic endothelial cells by D. Zapolska-Downar; D. Bryk; M. Małecki; K. Hajdukiewicz; D. Sitkiewicz (563-572).
Altered expression of cell adhesion molecules (CAMs) has been implicated in a variety of chronic inflammatory conditions, including atherosclerosis. Regulation of adhesion molecule expression by specific redox-sensitive mechanisms has been reported. Additionally, it has been observed that the extract of Aronia melanocarpa (A. Melanocarpa) fruits, rich in polyphenols, exhibits potent anti-oxidant properties and displays cardioprotective activity.Human aortic endothelial cells (HAECs) were pretreated with various concentrations (primarily 50 μg/mL) of Aronia Melanocarpa fruit extract prior to treatment with TNFα (10 ng/mL) for various periods of time. The surface protein and mRNA expression of ICAM-1 and VCAM-1 were determined using flow cytometry and real-time RT-PCR, respectively. Adhesion of peripheral blood mononuclear leucocytes (PBMLs) to TNFα-treated HAECs was evaluated by an adhesion assay. Activation of NF-κB was evaluated by measuring NF-κB p65 phosphorylation using flow cytometry. ROS production was determined by reduction in fluorescent 2′,7′-dichlorofluorescein diacetate (DCFH-DA). Tested A. Melanocarpa extract significantly inhibited the expression of ICAM-1 and VCAM-1, attenuated the phosphorylation of NF-κB p65 and decreased intracellular ROS production in TNFα-treated HAECs.We conclude that A. Melanocarpa fruit extract exhibits anti-inflammatory effects in HAECs by inhibiting the expression of endothelial CAMs, activation of NF-κB and production of ROS.
Keywords: Atherosclerosis; Cell adhesion molecules; Aronia Melanocarpa ; Nuclear factor-κB; Reactive oxygen species

Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and survival of prostate cancer cells treated with diallyl trisulfide by Alicja Sielicka-Dudzin; Andzelika Borkowska; Anna Herman-Antosiewicz; Michal Wozniak; Agnieszka Jozwik; Donatella Fedeli; Jedrzej Antosiewicz (573-581).
In our previous study, we demonstrated that diallyl trisulfide (DATS) induced iron-dependent G2-M arrest of prostate cancer cell cycle. Moreover, ferritin degradation and an increase of labile iron pool has been linked to the activation of the JNK signaling axis. In the present work, we extended this study to determine which of the c-jun kinases is responsible for ferritin degradation and the role of iron in DATS-induced cell death. We hypothesized that JNK1 activates Itch ligase which will lead to ferritin ubiquitination, an increase in iron-dependent ROS formation and cell death.PC-3 prostate cancer cells were used in this study. Cell viability, concentration of ROS, labile iron pool, and changes in ferritin and P-Itch and DNA damage were determined.We observed that DATS induced ferritin degradation through JNK, Itch signaling axis. DATS did not induce neither ROS formation nor increase the LIP in JNK1-DN transfected cells. We also observed that DATS increased JNK-dependent activating phosphorylation of E3ligase Itch. The cells transfected with inactive form of Itch were more resistant against cytotoxicity of DATS and showed lower DATS-induced ferritin degradation. Desferrioxamine a specific iron chelator had no effect neither on cell viability nor DNA damage evaluated by comet assay.These results suggest that JNK1-dependent increase in LIP is mediated by Itch ubiquitin ligase.
Keywords: Iron; Oxidative stress; Chemoprevention

Dairy intake, blood pressure and incident hypertension in a general British population: the 1946 birth cohort by Alexandros Heraclides; Gita D. Mishra; Rebecca J. Hardy; Johanna M. Geleijnse; Stephanie Black; Celia J. Prynne; Diana Kuh; Sabita S. Soedamah-Muthu (583-591).
We aimed to examine the association between intake of different subgroups of dairy products and blood pressure and incident hypertension 10 years later, adjusting for confounding factors.We studied 1,750 British men and women from the 1946 British birth cohort from 1989 to 1999 (age 43 and 53 years, respectively). Diet was assessed by 5-day food diaries using photographs in the estimation of portion size. Systolic (sbp) and diastolic (dbp) blood pressure and prevalent hypertension were assessed at age 43 and 53 years. Linear regression and logistic regression were used to examine 10-year blood pressure levels and incident hypertension by baseline dairy intake.There was a weak non-significant trend of a protective effect of total dairy intake on blood pressure and incident hypertension, but no evidence for a dose–response relationship (OR for incident hypertension: 0.88 (95% CI 0.68;1.14) 2nd vs. 1st tertile and 0.93 (95% CI 0.72;1.18) 3rd vs. 1st tertile). Higher intake of low-fat and fermented dairy was linked to a higher sbp but in a nonlinear manner. Adjustment for other dietary factors, health behaviours and BMI attenuated these associations.Total dairy intake and specific dairy subgroups were not associated with blood pressure and incident hypertension among a representative sample of British adults after adjustment for confounding factors.
Keywords: Dairy products; Blood pressure; Hypertension; Birth cohort; Epidemiology

Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice by Qing-Hua Hu; Xian Zhang; Xing Wang; Rui-Qing Jiao; Ling-Dong Kong (593-606).
Renal organic ion transporters and uromodulin (UMOD) play the important roles in renal urate excretion and function. Hyperuricemia is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin in diets exerts the hypouricemic and nephroprotective effects.To evaluate the effects of quercetin on renal organic ion transporters and UMOD in hyperuricemic mice.Kun-Ming mice were divided into normal and hyperuricemic groups receiving water, 25, 50 and 100 mg/kg quercetin, 5 mg/kg allopurinol, respectively. Hyperuricemic mice were orally gavaged with 250 mg/kg oxonate daily for 1 week. Quercetin and allopurinol were orally gavaged on the day when oxonate or water was given 1 h later. After 1 week, serum uric acid, creatinine and blood urea nitrogen concentrations, excretion of urate and creatinine, and fractional excretion of uric acid were measured. The mRNA and protein levels of renal urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in mice were analyzed. Simultaneously, UMOD levels in serum, urine and kidney, as well as renal UMOD mRNA expression were detected.Quercetin significantly restored oxonate-induced abnormalities of these biochemical indexes compared with normal vehicle group. Furthermore, it remarkably prevented expression changes of renal organic ion transporters and UMOD, and UMOD level alteration in hyperuricemic mice.These results suggest that quercetin has the uricosuric and nephroprotective actions mediated by regulating the expression levels of renal organic ion transporters and UMOD.
Keywords: Hyperuricemia; Renal dysfunction; Quercetin; Renal organic ion transporters; Uromodulin

A sodium-bicarbonated mineral water reduces gallbladder emptying and postprandial lipaemia: A randomised four-way crossover study by Laura Toxqui; Ana M. Pérez-Granados; Ruth Blanco-Rojo; M. Pilar Vaquero (607-614).
Sodium-bicarbonated mineral waters are reported to have beneficial digestive and hypocholesterolaemic properties. The aim of the study was to investigate the effects of consumption of a sodium-bicarbonated mineral water (BW) with or without a meal, compared to a low mineral content water as the control water (CW), on postprandial serum triacylglycerols (TAG), cholecystokinin (CCK) and gallbladder volume.The study design was a four-way randomised controlled crossover trial. Healthy adult men and women (>18 and <40 years, TAG <2.82 mmol/L) consumed 0.5 L of CW + standard meal; 0.5 L of BW + standard meal; and 0.5 L of CW without meal or 0.5 L of BW without meal.BW consumed without meal had no significant effect on the study parameters compared to CW. However, BW with meal induced a lower concentration of serum TAG at 30 min (p = 0.01) and 60 min (p = 0.03) postprandial times, lower CCK concentrations at 30 min (p = 0.002), and higher gallbladder volume at 30 min (p = 0.03), 60 min (p = 0.01) and 120 min (p = 0.04). Gallbladder ejection fraction was lower with the BW (p = 0.03), whilst area under the curve and peak contraction amplitude (lowest gallbladder volume) were higher (p = 0.01, p = 0.02, respectively) compared to the CW.Consumption of BW with a meal induces lower levels of CCK and reduces gallbladder emptying and postprandial TAG levels. It is proposed that this sodium-bicarbonated mineral water could be used as part of the habitual diet by the general population in order to reduce cardiovascular risk.
Keywords: Cardiovascular risk; Cholecystokinin; Gallbladder emptying; Humans; Postprandial triacylglycerols; Sodium-bicarbonated mineral water

Serum and lipoprotein sitostanol and non-cholesterol sterols after an acute dose of plant stanol ester on its long-term consumption by H. Gylling; M. Hallikainen; P. Simonen; H. E. Miettinen; M. J. Nissinen; T. A. Miettinen (615-622).
Chronic inhibition of cholesterol absorption with large doses of plant stanol esters (staest) alters profoundly cholesterol metabolism, but it is unknown how an acute inhibition with a large staest dose alters the postprandial serum and lipoprotein cholesterol precursor, plant sterol, and sitostanol contents.Hypercholesterolemic subjects, randomly and double-blind divided into control (n = 18) and intervention groups (n = 20), consumed experimental diet without and with staest (plant stanols 8.8 g/day) for 10 weeks. Next morning after a fasting blood sample (0 h), the subjects had a breakfast without or with staest (4.5 g of plant stanols). Blood sampling was repeated 4 h later. Lipoproteins were separated with ultracentrifugation, and sterols were measured with gas–liquid chromatography.In 0-h chylomicrons and VLDL, plant sterols were lower in staest than in controls. Postprandially, cholestenol (cholesterol synthesis marker) was reduced in chylomicrons in staest compared with controls (−0.13 ± 0.04 μg/dL vs. 0.01 ± 0.08 μg/dL, P < 0.05). Staest decreased postprandially avenasterol in chylomicrons (P < 0.05 from 0 h). Sitostanol was high at 0 h by chronic staest in serum and VLDL but not in chylomicrons. Postprandial sitostanol was increased by staest in VLDL only.Chronic cholesterol absorption inhibition with large amount of plant stanol esters decreases plant sterols in triglyceride-rich lipoproteins. Acute plant stanol ester consumption increases sitostanol content in triglyceride-rich lipoproteins but suggests to decrease the risk of plant sterol and plant stanol accumulation into vascular wall by chylomicrons.
Keywords: Plant stanol ester; Postprandium; Sitostanol; Sitosterol; Cholesterol synthesis; Cholesterol absorption

Vitamin C supplementation reconstitutes polyfunctional T cells in streptozotocin-induced diabetic rats by Gamal Badr; Samir Bashandy; Hossam Ebaid; Mohamed Mohany; Douaa Sayed (623-633).
Studies have demonstrated that vitamin C supplementation enhances the immune system, prevents DNA damage, and decreases the risk of a wide range of diseases. Other study reported that leukocyte vitamin C level was low in diabetic individuals compared with nondiabetic controls.To study the effect of vitamin C on oxidative stress, blood lipid profile, and T-cell responsiveness during streptozotocin (STZ)-induced type I diabetes mellitus.Thirty male Sprague–Dawley rats were randomly split into three groups. The first served as a control group (n = 10) in which rats were injected with the vehicle alone. The second (n = 10) and the third groups (n = 10) were rendered diabetic by intraperitoneal (i.p.) injection of single doses of STZ (60 mg/kg body weight). The third group was supplemented with vitamin C (100 mg/kg body weight) for 2 months.T lymphocytes from the diabetic rats were found to be in a stunned state, with a decreased surface expression of the CD28 costimulatory molecule, low levels of phosphorylated AKT, altered actin polymerization, diminished proliferation and cytokine production, and, eventually, a marked decrease in abundance in the periphery. Vitamin C was found to significantly decrease the elevated levels of blood hydroperoxide, glucose, cholesterol, triglycerides and low-density lipoprotein (LDL) in diabetic rats. Furthermore, it was found to restore CD28 expression, AKT phosphorylation, actin polymerization, and polyfunctional T cells (IFN-γ- and IL-2-producing cells that exhibit a high proliferation capacity).Vitamin C treatment restores and reconstitutes polyfunctional, long-lived T cells in diabetic rats.
Keywords: Diabetes mellitus; Oxidative stress; T-cell exhaustion and functions