Christian Ciardi

Effect of bariatric surgery on both functional and structural measures of premature atherosclerosis

AIMS To bridge the beneficial metabolic effects of pronounced weight loss on one side and the data on morbidity and mortality on the other side, we investigated the impact of profound weight loss on structural and functional markers of early atherosclerosis. METHODS AND RESULTS Thirty-seven obese adults were examined before and 18 months after bariatric surgery. Carotid intima-media thickness (CIMT), brachial flow-mediated dilation (FMD), nitroglycerine-mediated dilation, and abdominal fat distribution were assessed by high-resolution ultrasound. Surgery resulted in a body mass index decrease of 9.1 +/- 4.9 kg/m(2) with concomitant improvements in glucose and lipid metabolism. Carotid intima-media thickness diminished from 0.56 +/- 0.09 to 0.53 +/- 0.08 mm (n = 37; P = 0.004). Flow-mediated dilation improved from 5.81 +/- 3.25 to 9.01 +/- 2.93% (n = 25; P < 0.001). Both CIMT and FMD were associated with intra-abdominal fat diameter. CONCLUSION The present results demonstrate that bariatric surgery-induced diminution of visceral fat improves both functional and structural markers of early atherosclerosis, providing a link between the weight loss-associated improvements of traditional and non-traditional risk factors and the reduced long-term morbidity and mortality after bariatric surgery.

Effects of pronounced weight loss on Adiponectin oligomer composition and metabolic parameters

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters.

Food additives such as sodium sulphite, sodium benzoate and curcumin inhibit leptin release in lipopolysaccharide-treated murine adipocytes in vitro

Obesity leads to the activation of pro-inflammatory pathways, resulting in a state of low-grade inflammation. Recently, several studies have shown that the exposure to lipopolysaccharide (LPS) could initiate and maintain a chronic state of low-grade inflammation in obese people. As the daily intake of food additives has increased substantially, the aim of the present study was to investigate a potential influence of food additives on the release of leptin, IL-6 and nitrite in the presence of LPS in murine adipocytes. Leptin, IL-6 and nitrite concentrations were analysed in the supernatants of murine 3T3-L1 adipocytes after co-incubation with LPS and the food preservatives, sodium sulphite (SS), sodium benzoate (SB) and the spice and colourant, curcumin, for 24 h. In addition, the kinetics of leptin secretion was analysed. A significant and dose-dependent decrease in leptin was observed after incubating the cells with SB and curcumin for 12 and 24 h, whereas SS decreased leptin concentrations after 24 h of treatment. Moreover, SS increased, while curcumin decreased LPS-stimulated secretion of IL-6, whereas SB had no such effect. None of the compounds that were investigated influenced nitrite production. The food additives SS, SB and curcumin affect the leptin release after co-incubation with LPS from cultured adipocytes in a dose- and time-dependent manner. Decreased leptin release during the consumption of nutrition-derived food additives could decrease the amount of circulating leptin to which the central nervous system is exposed and may therefore contribute to an obesogenic environment.

A-FABP—A Biomarker Associated With the Metabolic Syndrome and/or an Indicator of Weight Change?

Objective: Adipocyte fatty acid‐binding protein (A‐FABP) is a plasma biomarker recently associated with the metabolic syndrome. The aim of these studies was to investigate changes of A‐FABP during profound weight loss induced by laparoscopic adjustable gastric banding (LAGB).

Immunoregulatory Impact of Food Antioxidants

Immune system activation and inflammation are deeply involved in the pathogenesis of a variety of diseases including infections, autoimmunity and malignancy as well as allergy and asthma. The incidence of allergy and asthma has significantly increased during the past decades. Still the background of this phenomenon is not well understood. The contribution of life style and habits are heavily discussed. Among them is a too clean environment which may predispose individuals to an increased sensitivity to allergic responses. Also dietary habits have changed drastically in the Western world, and it appears that especially the increased use of antioxidant food supplements, preservatives and colorants could be of relevance. In vitro experiments show that typical antioxidant compounds like vitamin C and E and the stilbene resveratrol as well as food preservatives such as sulfite, benzoate and sorbic acid and also colorants like curcumin exert significant suppressive effects on the T helper (h)1 immune activation cascade in freshly isolated human peripheral blood mononuclear cells. Obviously, antioxidant compounds interfere with central immunoregulatory pathways such as tryptophan breakdown via indoleamine 2,3-dioxygenase (IDO) and neopterin production by GTP-cyclohydrolase I (GCH). Results show an anti-inflammatory property of antioxidants which could shift the Th1-Th2-type immune balance towards Th2-type immunity that is of utmost importance in allergic responses. Additionally, food preservatives reduce the number of pathogens to which humans are exposed by their diet, so that in agreement with the hygiene hypothesis the likelihood of allergy might increase. This review article discusses the beneficial effects which antioxidants may have to counteract inflammatory diseases, but also their potential in the increase of allergy and asthma in the Western world and their involvement in the obesity epidemic.

Analysis of long-chain ω-3 fatty acid content in fish-oil supplements

ZusammenfassungHINTERGRUND: In zahlreichen Studien wurden die verschiedensten vorteilhaften Effekte von mehrfach ungesättigten Omega 3 Fettsäuren auf Atherosklerose, Arrhythmie und Hypertriglyzeridämie nachgewiesen, was zahlreiche Gesundheitsorganisationen dazu veranlasst hat, einen täglichen Verzehr von einem Gramm Omega 3 Fettsäuren täglich für antiatherosklerotische sowie antiarrhytmische Wirkungen oder zwei bis vier g/d Omega 3 Fettsäuren zur Senkung der Plasmatriglyzeride zu empfehlen. Es sind zahlreiche Präparate auf dem Markt erschienen, welche die ω-3 PUFA-arme westliche Ernährung in Form von Kapseln ergänzen. Da diese Präparate beträchtlichen Variationen des Gehalts an langkettigen ω-3 PUFAs unterworfen sein können, haben wir neun kommerziell erhältliche Produkte bezugnehmend auf ihre Fettsäurekomposition getestet. METHODEN: Neun kommerziell erhältliche ω-3 PUFA Nahrungsergänzungsmittel wurden mittels kapillärer Gaschromatographie auf ihren Gehalt an langkettigen ω-3 PUFA untersucht. ERGEBNISSE: Die neun von uns getesteten Präparate zeigen hinsichtlich der Konzentration an langkettigen ω-3 PUFA große Unterschiede von bis zu 63,7 ± 1,58 mol % (p = 0,002) und die Meisten scheitern daran, die empfohlene Tagesdosis von einem Gramm zu erzielen, selbst wenn sie in der höchsten vom Hersteller angegebenen Dosierung verabreicht werden. Acht der Präparate enthalten entweder gleiche oder signifikant höhere langkettige ω-3 PUFA Mengen als vom Hersteller angegeben und ein Hersteller macht keine Angabe. Die höchsten Anteile an Eicosapentaensäure (EPA) und Docosahexaensäure (DHA) wurden in Omacor® (95,80 ± 0,63%) und Percucor® (76,8 ± 7,11%) vorgefunden. KONKLUSION: Verabreichung von langkettigen ω-3 Fettsäurepräparaten kann in großen Unterschieden der tatsächlich konsumierten Menge resultieren. Daher ist es empfehlenswert, die am höchsten standardisierten und gereinigten Produkte zu verwenden.SummaryBACKGROUND: Omega-3 polyunsaturated fatty acids (long-chain ω-3 PUFA) have proved to be beneficial in atherosclerosis, arrhythmia and hypertriglyceridemia in several studies, which has led national and international societies to recommend an intake of 1 g/d long-chain ω-3 PUFA for antiatherosclerotic and antiarrhythmic purposes or 2–4 g/d for a lipid lowering effect. Numerous preparations are marketed for supplementing western diet, which is low in long-chain ω-3 PUFA. Since these preparations vary in their long-chain ω-3 PUFA content, we tested nine commercially available products for their fatty acid composition. METHODS: Nine commercially available ω-3 fatty acid supplements were analyzed using capillary gas chromatography to determine their fatty acid content. RESULTS: The nine preparations showed huge differences, up to 63.7 ± 1.58 mol% (P = 0.002), in their longchain ω-3 fatty acid content. Most of them failed to achieve the daily recommended dose of 1 g, even when administered at the highest dosage according to the manufacturers recommendations. Eight of the preparations contained either equal or significantly greater amounts of long-chain ω-3 PUFA than denoted by the manufacturer; one preparation did not provide any information. The highest percentage of DHA and EPA was detected in Omacor® (95.80 ± 0.63%) and Percucor® (76.8 ± 7.109%). CONCLUSION: Administering long-chain ω-3 fatty acid preparations may result in huge differences in terms of the actual amount ingested. It is therefore advisable to use the most standardized and purified products available.

Influence of significant weight loss on serum matrix metalloproteinase (MMP)-7 levels

BACKGROUND Matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitor of metalloproteinases [TIMPs]), are involved in adipogenesis, angiogenesis and remodeling of extracellular matrix. MMPs and TIMPs have been shown to be associated with various diseases such as neurological disorders, malignancies and cardiovascular disease. MMPs and TIMPs are thought to play a major role in extensive reorganization of the adipose tissue in obesity. METHODS AND MATERIALS To test whether significant weight loss alters circulating MMPs and TIMPs, 18 morbidly obese women, who underwent bariatric surgery for weight loss, were investigated before and one year after surgery in a prospective design study. Body composition, glucose and lipid metabolism parameters were determined in all study subjects before and after weight loss. Circulating MMP-2, -3, -7 and TIMP-1, -2 and -4 serum levels were measured using commercially available, enzyme-linked immunoassays. RESULTS Pronounced weight loss was accompanied by improvements in glucose homeostasis and lipid parameters. In the mean time MMP-2 and MMP-3, as well as TIMP-1, -2 and TIMP-4 concentrations were not affected by significant weight loss, and circulating MMP-7 increased significantly after bariatric surgery, although without reaching the standard levels as determined in 18, lean, healthy women. CONCLUSION Our data indicate that reduced MMP-7 levels in obesity might be restored by significant weight loss, suggesting that the reorganization of adipose tissue in obesity might be partially reversible by weight reduction. We hypothesize that increased circulating MMP-7 might indicate enhanced adipocyte differentiation in subjects who had undergone bariatric surgery.

Adiponectin receptor R1 is upregulated by valproic acid but not by topiramate in human hepatoma cell line, HepG2

Valproic acid (VPA) is an effective and widely used anticonvulsant, associated with metabolic adverse effects such as weight gain, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia. The aim of this study was to evaluate the influence of VPA and topiramate (TPM) on adiponectin binding receptors, adipoR1 and adipoR2, in human liver cancer cells, HepG2. AdipoR1 but not adipoR2 gene expression was upregulated by VPA treatment. TPM did neither affect adipoR1 nor adipoR2 gene expression. Given the tight association between VPA treatment, metabolic side effects and the adipocytokine-axis, upregulation of adipoR1 possibly represents a favoured and insulin-sensitizing mechanism.

Resistin impairs basal and insulin-induced glycogen synthesis by different mechanisms.

In the present study, we investigated the mechanisms by which resistin (100 nM, 1 h) affects glycogen synthesis in L6 skeletal muscle cells. The activity of glycogen synthase, the major enzyme in glycogen synthesis, is determined by both its covalent phosphorylation and allostery through intracellular glucose-6-phosphate. Covalent phosphorylation of glycogen synthase was not altered by resistin and, accordingly, phosphorylation of GSK-3alpha/beta and Akt remained unchanged. The rate of glucose-6-phosphate formation, however, was decreased by resistin both in the absence and presence of insulin; in the absence of insulin, resistin decreased glucose-6-phosphate formation by reducing hexokinase type I activity without affecting glucose uptake; by contrast, in the presence of insulin, resistin decreased glucose-6-phosphate formation by reducing the Vmax of glucose uptake without changing hexokinase type I activity. In conclusion, short-term resistin incubation impairs glycogen synthesis by reducing the rate of glucose-6-phosphate formation involving, however, differential mechanisms in basal and insulin-stimulated states.

Postprandial triglyceride-rich lipoproteins induce hepatic insulin resistance in HepG2 cells independently of their receptor-mediated cellular uptake

Highlights ► The pathophysiological link between NAFLD and hepatic insulin resistance is unknown. ► We studied the effect of postprandial lipoproteins on hepatic insulin sensitivity. ► Postprandial lipoproteins cause liver steatosis and hepatic insulin resistance. ► We characterize the underlying molecular mechanisms. ► Postprandial lipoproteins are a link between NAFLD and hepatic insulin resistance.