Pubblicazioni

Autore: Akira Nakajima, Alexis Vogelzang, Mikako Maruya, Michio Miyajima, Megumi Murata, Aoi Son, Tomomi Kuwahara, Tatsuaki Tsuruyama, Satoshi Yamada, Minoru Matsuura, Hiroshi Nakase, Daniel A. Peterson, Sidonia Fagarasan, and Keiichiro Suzuki
Rivista: Journal of Experimental Medicine

Immunoglobulin A (IgA) promotes health by regulating the composition and function of gut microbiota, but the molecular requirements for such homeostatic IgA function remain unknown. We found that a heavily glycosylated monoclonal IgA recognizing ovalbumin coats Bacteroides thetaiotaomicron (B. theta), a prominent gut symbiont of the phylum Bacteroidetes. In vivo, IgA alters the expression of polysaccharide utilization loci (PUL), including a functionally uncharacterized molecular family provisionally named Mucus-Associated Functional Factor (MAFF). In both mice and humans, MAFF is detected predominantly in mucus-resident bacteria, and its expression requires the presence of complex microbiota. Expression of the MAFF system facilitates symbiosis with other members of the phylum Firmicutes and promotes protection from a chemically induced model of colitis. Our data reveal a novel mechanism by which IgA promotes symbiosis and colonic homeostasis.

Autore: Wei WANG, Shandong YE, Liting QIAN, Xuenong XING
Rivista: J Nutr Sci Vitaminol (Tokyo)

This study aimed to explore the association between serum 25-hydroxyvitamin D (25(OH)D) and insulin resistance as well as β-cell function in Chinese Han patients with newly diagnosed type 2 diabetes mellitus (T2DM). A total of 264 patients was included in this study. Serum 25(OH)D, plasma glucose, serum insulin and other biochemical parameters were assayed. Postprandial venous blood was collected after a mixed-nutrient load. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (Matsuda ISI). The β-cell function was assessed by the homeostasis model assessment for insulin secretion (HOMA-β) and the change in insulin divided by change in glucose from 0 to 30 min (ΔI0-30/ΔG0-30). Patients were divided into three groups according to tertiles of serum 25(OH)D levels. There were significant differences in HOMA-IR and Matsuda ISI among the three groups (HOMA-IR, p=0.005; Matsuda ISI, p=0.009). Pearson correlation analyses showed that serum 25(OH)D was negatively correlated with fasting serum insulin (FIns) (r=−0.209, p=0.012) and HOMA-IR (r=−0.273, p=0.001), and positively correlated with Matsuda ISI (r=0.219, p=0.009) only in the male population. Multiple stepwise regression analyses showed that in the male population, serum 25(OH)D was an independent predictor for both HOMA-IR and Matsuda ISI before and after adjustment for confounding factors, respectively (p<0.05 for both). This study indicates the association of vitamin D with insulin resistance in male patients with newly diagnosed T2DM, which may contribute to the understanding of the mechanism underlying the onset of T2DM in the Chinese Han population.

Autore: Jianling Bai Pengcheng Xun, Steve Morris, David R. Jacobs Jr., Kiang Liu & Ka He
Rivista: Nature

Studies suggest that chromium deficiency is associated with elevated levels of fasting blood glucose, circulating insulin, cholesterol and triglycerides, and decreased proportion of lean body mass. However, data directly relating chromium levels to metabolic syndrome (MetS) risk are lacking. A total of 3,648 American adults from the Coronary Artery Risk Development in YoungAdults (CARDIA) study, aged 20–32 years, were prospectively examined for the incidence of MetS and its five components from 1987–88 to 2010–11. Baseline toenail chromium levels were measured with instrumental neutron-activation analysis. Incident MetS was defined by the NCEP-ATP III criteria. During the 23-year follow-up, 878 incident MetS cases were identified. Baseline toenail chromium was inversely associated with incidence of MetS as well as its blood lipid components. The multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of MetS comparing the highest to the lowest quartiles of toenail chromium levels was 0.80 (0.66–0.98; Plinear trend = 0.006). The adjusted HRs were 0.82 (0.68–0.98; Ptrend = 0.045) for having abnormal triglycerides levels and 0.75 (0.64–0.88; Ptrend = 0.030) for having abnormal HDL cholesterol levels. Toenail chromium levels were inversely and longitudinally associated with incidence of MetS in American young adults. This inverse association was mainly explained by its relation to blood lipids.

Autore: M. Hummel , E. Standl , O. Schnell
Rivista: Hormone and Metabolic Research · November 2007

Chromium is an essential mineral that appears to have a benefi cial role in the regulation of insulin action, metabolic syndrome, and cardiovascular disease.

There is growing evidence that chromium may facilitate insulin signaling and chromium supplementation therefore may improve systemic insulin sensitivity. Tissue chromium levels of subjects with diabetes are lower than those of normal control subjects, and a correlation exists between low circulating levels of chromium and the incidence of type 2 diabetes. Controversy still exists as to the need for chromium supplementation. However, supplementation with chromium picolinate, a stable and highly bioavailable form of chromium, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Since chromium supplementation is a safe treatment, further research is necessary to resolve the confounding data. The existing data suggest to concentrate future studies on certain forms as chromium picolinate and doses as at least 200 mcg per day.

Autore: Hua J Kern Susan Hazels Mitmesser
Rivista: Nutrition and Dietary Supplements 2018

Abstract: Metabolic syndrome (MetS) and its associated chronic disorders including cardiovascular disease and type 2 diabetes are public health concerns in the USA and worldwide. “Good health is an investment in economic growth,” and nutrition is one of the recommended preventive measures to manage these chronic diseases. However, it is unclear whether and to what extent nutrients could be beneficial to the improvement of MetS. To help answer this question, we performed a literature review of the emerging human data on single nutrients and MetS: PubMed was searched from January 1, 2005 to June 12, 2017, using a combination of the following keywords: “nutrient” OR “vitamin” OR “mineral” OR “nutraceutical” AND “metabolic syndrome.” The summary of literature comprises macronutrients (proteins/amino acids, fatty acids, fibers, and sugar), micronutrients (antioxidant vitamins, vitamin D, folate, magnesium, and chromium), polyphenols (flavonoids, resveratrol, isoflavones, and chlorogenic acid), and other compounds (α-lipoic acid, benfotiamine, fucoxanthin, policosanol, and stanols). Bearing a holistic approach in mind, we also highlighted select lifestyle factors that may contribute to MetS (such as circadian rhythm and nutrition in early life). Observational studies have generated positive evidence supporting the beneficial role of numerous nutrients in MetS. Although the results of some clinical trials are consistent with the observational data, causality is not always clear or consistent across trials. Both nutrition and health are complex and dynamic systems with a hierarchical nature. When we design confirmatory trials to investigate nutrient(s) and MetS, instead of the traditional “single-nutrient” concept, it is worth considering a holistic approach to integrate groups or classes of nutrients, lifestyle influencers (ie, diet and physical activity), and population relevance (ie, healthy, at-risk, or diseased).

 
Autore: Eliana Piantanida,Daniela Gallo, Giovanni Veronesi, Eugenia Dozio, Eugenia Trotti, Adriana Lai, Silvia Ippolito, Jessica Sabatino, Maria Laura Tanda, Antonio Toniolo, Marco Ferrario and Luigi Bartalena
Rivista: Endocrine Connections (2017)

Objective: The aim of this observational study was to clarify the link between vitamin D status and metabolic syndrome (MetS) in people with visceral obesity. Design and methods: One hundred ninety-six consecutive patients (152 women; mean age 51 ± 13 years) with visceral obesity (mean body weight 103 ± 20 kg, mean waist circumference (WC) 119 ± 13 cm) were enrolled at the Obesity Outpatient Clinic of the University of Insubria in Varese. Anthropometric measurements were recorded. Laboratory tests, including vitamin D (25(OH)D)), fasting blood glucose (FBG), lipid profile, liver and kidney function tests were assessed. Vitamin D status was defined according to the European Society of Endocrinology guidelines, MetS to the 2009 harmonized definition. Results: An inverse association emerged among 25(OH)D, body mass index (BMI) (P = 0.001) and WC (all P = 0.003). Serum 25(OH)D levels were inversely related to FBG and systolic blood pressure (SBP) (respectively, P = 0.01 and 0.02). Median serum 25(OH) D levels were 13.3 ng/mL (CI 95% 12; 15) in MetS and 16 ng/mL (CI 95% 14; 18) (P = 0.01) in non-MetS patients. Among patients with MetS, lower 25(OH)D concentrations were related to higher risk of hypertension (HT) (odds ratio (OR) 1.7, CI 95%, 0.7;4) and hyperglycemia (IFG)/type 2 diabetes (OR 5.5, CI 95% 2; 14). Conclusion: Vitamin D status and MetS are inversely correlated in visceral obesity, particularly with regard to glucose homeostasis and BP. More extensive studies are required to investigate the potential for causality.

Autore: Yan Yang, Xuejun Zhang, Mingjing Bao, Limei Liu, Yang Xian, Jichuan Wu, Pengqiu Li
Rivista: J Diabetes Investig Vol. 7 No. 2 March 2016

Aims/Introduction: To evaluate serum 25-hydroxyvitamin D3 (25(OH)D3) in newly diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D3 with insulin resistance and b-cell function. Materials and Methods: A total of 97 newly diagnosed type 2 diabetes patients and 69 healthy controls were recruited. Serum 25(OH)D3 was determined using high-pressure liquid chromatography. Insulin resistance was measured using a homeostasis model assessment of insulin resistance (HOMA-IR). b-Cell function was determined using the HOMA b-cell function index (HOMA-b), early-phase insulin secretion index (DI30/DG30) and area under the insulin curve (AUCins). Correlation analysis was carried out using Pearson’s correlation and multiple stepwise regression analysis. Results: Serum 25(OH)D3 was much lower in patients with newly diagnosed type 2 diabetes(t = -13.00, P < 0.01), and the prevalence of hypovitaminosis 25(OH)D3 was 62.9% (61/97) in diabetic patients. Among the diabetic patients, patients with hypovitaminosis 25 (OH)D3 showed higher glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA-b, DI30/DG30 and AUCins. Serum 25(OH)D3 was independently positively correlated with DI30/DG30 and AUCins (P < 0.05), but was not significantly correlated with either HOMA-IR or HOMA-b. Only triglycerides, glycosylated hemoglobin and DI30/DG30 emerged as independent factors associated with serum 25(OH)D3 in both diabetes patients and the health control group. Conclusions: The present results further showed a low serum 25(OH)D3 concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D3 deficiency is associated with disturbances in glucose metabolism and lipid metabolism. Serum 25(OH)D3 is not correlated with basal insulin resistance or b-cell function, but is significantly positively correlated with glucose-stimulated insulin secretion and b cell function.

Autore: Francis C. Lau Æ Manashi Bagchi Æ Chandan K. Sen Æ Debasis Bagchi
Rivista: Molecular and Cellular Biochemistry · October 2008

Abstract Insulin resistance has been shown to be the major contributing factor to the metabolic syndrome, which comprises a cluster of risk factors for metabolic aberrations such as obesity, dyslipidemia, hypertension, and hyperglycemia. Additionally, insulin resistance has been associated with the occurrence of cardiovascular disease and type 2 diabetes. Epidemiological studies indicate that obesity and diabetes have become alarmingly prevalent in recent years. Substantial evidence suggests that dietary interventions and regular exercise greatly improve body mass index and lipid profile as well as alleviate insulin resistance. Therefore, dietary supplements such as insulinsensitizing agents may be beneficial in the prevention and treatment of obesity and type 2 diabetes. Numerous in vitro and in vivo studies suggest that chromium supplements, particularly niacin-bound chromium or chromium-nicotinate, may be effective in attenuating insulin resistance and lowering plasma cholesterol levels. Utilizing the powerful technology of nutrigenomics to identify the genes regulated by chromium supplementation may shed some light on the underlying mechanisms of chromium-gene interactions, and thus provide strategies to mitigate and prevent insulinresistance-related disorders.

Autore: Takuya Matsumura,Takanobu Kato, Nao Sugiyama, Megumi Tasaka-Fujita, Asako Murayama,Takahiro Masaki,Takaji Wakita,and Michio Imawari
Rivista: HEPATOLOGY, October 2012

Because the current interferon (IFN)-based treatment for hepatitis C virus (HCV) infection has a therapeutic limitation and side effects, a more efficient therapeutic strategy is desired. Recent studies show that supplementation of vitamin D significantly improves sustained viral response via IFN-based therapy. However, mechanisms and an active molecular form of vitamin D for its anti-HCV effects have not been fully clarified. To address these questions, we infected HuH-7 cells with cell culture-generated HCV in the presence or absence of vitamin D3 or its metabolites. To our surprise, 25 hydroxyvitamin D3 [25(OH)D3], but not vitamin D3 or 1,25-dihydroxyvitaminD3, reduced the extra- and intracellular levels ofHCV core antigen in a concentration-dependent manner. Single-cycle virus production assay with a CD81- negative cell line reveals that the inhibitory effect of 25(OH)D3 is at the level of infectious virus assembly but not entry or replication. Long-term 25(OH)D3 treatment generates a HCV mutant with acquired resistance to 25(OH)D3, and this mutation resulting in a N1279Y substitution in the nonstructural region 3 helicase domain is responsible for the resistance. Conclusion: 25(OH)D3 is a novel anti-HCV agent that targets an infectious viral particle assembly step. This finding provides insight into the improved efficacy of anti-HCV treatment via the combination of vitamin D3 and IFN. Our results also suggest that 25(OH)D3, not vitamin D3, is a better therapeutic option in patients with hepatic dysfunction and reduced enzymatic activity for generation of 25(OH)D3. (HEPATOLOGY 2012;56:1231-1239)

Autore: Meital Gal-Tanamy,Larisa Bachmetov,Amiram Ravid Ruth Koren,Arie Erman, Ran Tur-Kaspa,and Romy Zemel
Rivista: HEPATOLOGY, Vol. 54, No. 5, 2011

Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D3 remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin D hormonally active metabolite, calcitriol. Treatment with vitamin D3 resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin D3 has an antiviral activity which is mediated by its active metabolite. This antiviral activity involves the induction of the interferon signaling pathway, resulting in expression of interferon-b and the interferon-stimulated gene, MxA. Intriguingly, HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin D3 or calcitriol and interferon-a synergistically inhibited viral production. Conclusion: This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system. It proposes an interplay between the hepatic vitamin D endocrine system and HCV, suggesting that vitamin D has a role as a natural antiviral mediator. Importantly, our study implies that vitamin D might have an interferon-sparing effect, thus improving antiviral treatment of HCV infected patients. (HEPATOLOGY 2011;54:1570-1579)