1. |
- Ferro, Y., et al.
(author)
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Effect of a novel functional tomato sauce (OsteoCol) from vine-ripened tomatoes on serum lipids in individuals with common hypercholesterolemia: tomato sauce and hypercholesterolemia
- 2021
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In: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: Most studies focused on the benefits of lycopene on serum lipids but no studies have been specifically designed to assess the role of a tomato sauce from vine-ripened tomatoes on patients affected by polygenic hypercholesterolemia. The aim of this study was to compare the lipid-lowering effect of a novel functional tomato sauce with a well-known functional food with a lipid-lowering effect, i.e. a sterol-enriched yogurt. Methods: In this cross-over study, we evaluated a population of 108 ambulatory patients affected by polygenic hypercholesterolemia of both gender, who were allocated to a tomato sauce (namely OsteoCol) 150 ml/day or a sterol-enriched yogurt (containing sterols 1.6 g/die) treatment, for 6 weeks. Carotenoids content was 3.5 mg per gram of product. We measured serum lipids and creatinine and transaminases at basal and follow-up visit. Results: A total of 91 subjects completed the protocol. A significant difference in LDL-cholesterol change was found between participants taking yogurt, tomato sauce (high adherence) and tomato sauce (low adherence) (- 16; - 12; + 8 mg/dl respectively; p < 0.001). We found a greater LDL-cholesterol reduction in the participants with a basal LDL-cholesterol more than 152 mg/dl (15% for sterol-enriched yogurt and 12% for tomato sauce at high adherence). Conclusion: A novel functional tomato sauce from vine-ripened tomatoes compares favourably with a commercialised sterol-enriched yogurt in term of absolute LDL-cholesterol change. Intake of a tomato sauce with a high carotenoid content may support treatment of patients affected by common hypercholesterolemia. The present study has various limitations. The presence of other dietary components, which may have influenced the results, cannot be ruled out. Of course, these results cannot be extrapolated to other populations. Furthermore, there was a low adherence rate in the tomato sauce group. Moreover, we did not report serum carotenoids data. Trial registration: ID: 13244115 on the ISRCTN registry, retrospectively registered in 2019-5-14. URL: http://www.isrctn.com/ISRCTN13244115
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2. |
- Pujia, R., et al.
(author)
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Liver Stiffness in Obese Hypothyroid Patients Taking Levothyroxine
- 2022
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In: Medicina-Lithuania. - : MDPI AG. - 1010-660X. ; 58:7
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Journal article (peer-reviewed)abstract
- Background and Objectives: Thyroid dysfunction is associated with non-alcoholic fatty liver disease, but its role in the progression of liver damage in obese patients remains unclear. In addition, several case reports have suggested the existence of a levothyroxine-induced liver injury, which has been poorly investigated. Our aim was to verify whether a difference in the prevalence of liver fibrosis exists in a population of obese individuals taking Levothyroxine. Materials and Methods: We conducted a cross-sectional study on a population of 137 obese individuals, of which 49 were on replacement therapy with Levothyroxine. We excluded those who had hypertriglyceridemia and diabetes mellitus. All participants underwent a liver stiffness assessment by transient elastography as well as biochemical measurements. In subjects with liver fibrosis, other cause of liver fibrosis were ruled out. Results: Participants taking Levothyroxine had a higher prevalence of liver fibrosis than those not taking Levothyroxine (30.6% vs. 2.3%; p < 0.001), and these results were obtained after we made an adjustment for age (Exp(B) = 18.9; 95% CI = 4.1-87.4; p < 0.001). The liver stiffness value differed significantly between groups (6.0 +/- 3.6 and 5.1 +/- 1.2, p = 0.033). Of those subjects taking Levothyroxine, there were no significant differences in the dose of medication (1.21 +/- 0.36 vs. 1.07 +/- 0.42; p = 0.240) and treatment duration (13.7 +/- 7.43 vs. 11.13 +/- 6.23; p = 0.380) between those with and without liver fibrosis. Conclusions: We found, for the first time, a greater prevalence of liver fibrosis in obese individuals taking Levothyroxine than in those not taking this medication. This finding needs to be confirmed by longitudinal population studies as well as by cellular studies.
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3. |
- De Vincentis, A., et al.
(author)
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Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
- 2022
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 46, s. 486-493
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Journal article (peer-reviewed)abstract
- Background Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined. Objectives To identify the independent risk factors for SLD among participants with obesity from the UK Biobank. Methods A total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m(2)) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA). Results Obesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03-1.07, p = 3.9 * 10(-7)), type 2 diabetes (aHR 2.18, 95%CI 1.55-3.05, p = 6.2 * 10(-6)), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33-1.9, p = 3.1 * 10(-7)) and WC (aHR 1.04, 95%CI 1.02-1.06, p = 8.5 * 10(-6)) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m(2) and WC above BMI-category specific thresholds. Conclusions Age, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds.
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4. |
- Ferro, Y., et al.
(author)
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Fat utilization and arterial hypertension in overweight/obese subjects
- 2013
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In: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 11:159
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Journal article (peer-reviewed)abstract
- Background: The Respiratory Quotient is a parameter reflecting the utilization of the nutrients by a subject. It is associated with an high rate of subsequent weight gain and with the atherosclerosis. Subjects tending to burn less fat have an increased Respiratory Quotient. Aim of this study was to investigate on the relationship between the Respiratory Quotient and the cardiovascular risk factors. Methods: In this cross-sectional study we enrolled 223 individuals of both sexes aged 45- 75 ys that were weight stable, receiving a balanced diet, and not affected by debilitating disease or cardiovascular disease. The Respiratory Quotient was measured by Indirect Calorimetry. The measurement of the Blood Pressure was obtained by a mercury sphygmomanometer. Results: We enrolled 133 female and 90 male. Systolic blood pressure only was positively correlated to the Respiratory Quotient in univariate and multivariate regression analysis (p= 0,017). The prevalence of hypertension was significatively different between the quartiles of the Respiratory Quotient, with the highest prevalence in the IV quartile (p= 0,024). Conclusion: High value of the Respiratory Quotient, an index of nutrients utilization, is associated to an high prevalence of Hypertension. It is possible that in the subjects with high Respiratory Quotient and high body mass index, the activation of the renin angiotensin system, in concert to the reduction of the utilization of the endogenous fat stores, could increase the risk of hypertension.
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5. |
- Mare, R., et al.
(author)
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A Rapid and Cheap Method for Extracting and Quantifying Lycopene Content in Tomato Sauces: Effects of Lycopene Micellar Delivery on Human Osteoblast-like Cells
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 14:3
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Journal article (peer-reviewed)abstract
- Identifying and quantifying the beneficial molecules contained in nutraceuticals is essen-tial to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lyco-pene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/β-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lyco-pene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol® lycopene extract increased ALP and β-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p < 0.05 respectively). In con-clusion, despite both techniques showing similar final results, UV/VIS spectrophotometer is prefer-able to HPLC due to its cheap, rapid, and accurate results, as well as for the opportunity to analyze lycopene-loaded micelles. The extraction and release of lycopene to bone cells positively influences the differentiation of osteoblasts and increases the expression of the ALP and β-catenin proteins. As a consequence, as a lycopene-rich sauce, Osteocol® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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6. |
- Maurotti, S., et al.
(author)
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Effects of a Functional Ice Cream Enriched with Milk Proteins on Bone Metabolism: A Feasibility Clinical Study and In Vitro Investigation
- 2023
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 15:2
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Journal article (peer-reviewed)abstract
- Background: Milk proteins (MPs) and their derivative whey proteins (WPs) are important components of human diet that might prevent bone loss. We aimed to investigate the effects of MP on the bones of postmenopausal women, along with the effects of WP on osteoblast cells. Methods: We conducted a feasibility controlled clinical study with 62 postmenopausal women who were asked to consume an MP-enriched ice cream. We also investigated the effect of WP on the ERK1/2 and AKT pathways, RUNX2, alkaline phosphatase, RANKL/OPG ratio, and COL1A of Saos-2. Results: After 12 weeks, we found a greater bone mineral density and bone alkaline phosphatase reduction in women who consumed the MP-enriched ice cream compared to the control group (p = 0.03 and p = 0.02, respectively). In Saos-2 cells, WP upregulated ERK1/2 and AKT pathways (p = 0.002 and p = 0.016), cell proliferation (p = 0.03), and osteoblast differentiation markers, along with downregulating RANKL/OPG (p < 0.001). Moreover, the inhibition of ERK1/2 by PD184253 reverted the effects on both the RUNX2 and ALP mRNA expression and cells proliferation (p = 0.028, p = 0.004, and p = 0.003, respectively) when treated with WP. Conclusions: WP upregulates cell proliferation, RUNX2, and alkaline phosphatase through the activation of the ERK1/2 pathways on Saos-2. These mechanisms probably contribute to preventing bone loss in postmenopausal women.
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7. |
- Maurotti, S., et al.
(author)
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Preventing muscle wasting: pro-insulin C-peptide prevents loss in muscle mass in streptozotocin-diabetic rats
- 2023
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In: Journal of Cachexia Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 14:2, s. 1117-1129
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Journal article (peer-reviewed)abstract
- BackgroundC-peptide therapy exerts several positive actions on nerves, vasculature, smooth muscle relaxation, kidney function and bone. To date, the role of C-peptide in preventing type 1 diabetes-related muscle atrophy has not been investigated. Our aim was to evaluate if C-peptide infusion prevents muscle wasting in diabetic rats. MethodsTwenty-three male Wistar rats were randomly divided into three groups: normal control group, diabetic group and diabetic group plus C-peptide. Diabetes was induced by streptozotocin injection, and C-peptide was administered subcutaneously for 6 weeks. The blood samples were obtained at baseline, before streptozotocin injection and at the end of the study to assess C-peptide, ubiquitin and other laboratory parameters. We also tested the ability of C-peptide to regulate the skeletal muscle mass, the ubiquitin-proteasome system, the autophagy pathway as well as to improve muscle quality. ResultsC-peptide administration reversed hyperglycaemia (P = 0.02) and hypertriglyceridaemia (P = 0.01) in diabetic plus C-peptide rats compared with diabetic control rats. The diabetic-control animals displayed a lower weight of the muscles in the lower limb considered individually than the control rats and the diabetic plus C-peptide rats (P = 0.03; P = 0.03; P = 0.04; P = 0.004, respectively). The diabetic-control rats presented a significantly higher serum concentration of ubiquitin compared with the diabetic plus C-peptide and the control animals (P = 0.02 and P = 0.01). In muscles of the lower limb, the pAmpk expression was higher in the diabetic plus C-peptide than the diabetic-control rats (in the gastrocnemius, P = 0.002; in the tibialis anterior P = 0.005). The protein expression of Atrogin-1 in gastrocnemius and tibialis was lower in the diabetic plus C-peptide than in diabetic-control rats (P = 0.02, P = 0.03). After 42 days, the cross-sectional area in the gastrocnemius of the diabetic plus C-peptide group had been reduced by 6.6% while the diabetic-control rats had a 39.5% reduction compared with the control animals (P = 0.02). The cross-sectional area of the tibialis and the extensor digitorum longus muscles was reduced, in the diabetic plus C-peptide rats, by 10% and 11%, respectively, while the diabetic-control group had a reduction of 65% and 45% compared with the control animals (both P < 0.0001). Similar results were obtained for the minimum Feret's diameter and perimeter. ConclusionsC-peptide administration in rats could protect skeletal muscle mass from atrophy induced by type 1 diabetes mellitus. Our findings could suggest that targeting the ubiquitin-proteasome system, Ampk and muscle-specific E3 ubiquitin ligases such as Atrogin-1 and Traf6 may be an effective strategy for molecular and clinical intervention in the muscle wasting pathological process in T1DM.
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8. |
- Pujia, A., et al.
(author)
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Lipid Oxidation Assessed by Indirect Calorimetry Predicts Metabolic Syndrome and Type 2 Diabetes
- 2019
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In: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 9
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Journal article (peer-reviewed)abstract
- Purpose: Diabetes has been linked to an impaired ability to oxidize fatty acids. Fat oxidation can be assessed clinically by a respiratory quotient measurement during fasting. We hypothesized that a respiratory quotient might predict metabolic syndrome and type 2 diabetes onset. Methods: In this longitudinal study we used an existing database of 233 individuals who had complete nutritional and biochemical data at baseline and after 12-month follow-up. All participants underwent an indirect calorimetry to measure the respiratory quotient. We excluded participants with diabetes, metabolic syndrome, chronic diseases, and those who had changed food habits in the previous 3 months. Only 88 subjects met the inclusion criteria. Results: Two individuals developed type 2 diabetes and 10 metabolic syndrome after 1 year. Participants in the high respiratory quotient group (>0.91) had a higher incidence of metabolic syndrome/diabetes than those in the low quotient group (25 vs. 8% p = 0.04). In this group, mean basal respiratory quotient was 0.97 +/- 0.04. In the high respiratory quotient group, Kaplan-Meier curves showed a greater probability of having metabolic syndrome/diabetes than those in the low respiratoryquotient group (log Rank chi(2)-test = 8.44; p = 0.004). A multivariable Cox proportional hazards model demonstrated that energy expenditure and weight increase did not predict metabolic syndrome/diabetes [HR (95% CI) = 1 (0.996-1.005), p = 0.86 and 3.9 (0.407-38.061), p = 0.23, respectively). Conclusions: A greater probability of metabolic syndrome/diabetes was found in individuals with a basal respiratory quotient of >0.91 than in those with a respiratoryquotient of <= 0.91 after 1 year. In the short-term anthropometric measurements and their variation overtime were not correlated with metabolic syndrome/diabetes.
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9. |
- Russo, C., et al.
(author)
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Lycopene and bone: an in vitro investigation and a pilot prospective clinical study
- 2020
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In: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 18:1
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Journal article (peer-reviewed)abstract
- Background There are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women. Methods We investigated the effect of lycopene on the Wnt/beta-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women. Results Lycopene 10 mu M resulted in higher beta-catenin and phERK1/2 protein Vs the vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 mu M doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p < 0.05). A significant bone density loss was not detected in women taking the tomato sauce while the control group had bone loss (p = 0.002). Tomato sauce intake resulted in a greater bone alkaline phosphatase reduction than the control (18% vs 8.5%, p = 0.03). Conclusions Lycopene activates the WNT/beta-catenin and ERK1/2 pathways, upregulates RUNX2, alkaline phosphatase, COL1A and downregulates RANKL Saos-2. These processes contributed to prevent bone loss in postmenopausal women.
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10. |
- Bailetti, D., et al.
(author)
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ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with obesity
- 2019
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In: Obesity Science & Practice. - : Wiley. - 2055-2238. ; 5:1, s. 83-90
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Journal article (peer-reviewed)abstract
- Objective ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. Methods ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. Results Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 x 10(-9)). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia (p = 0.0106). Conclusions In participants with obesity the ANGPTL4-E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.
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