| 1. |
- Maurotti, Samantha, et al.
(författare)
-
Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats.
- 2020
-
Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 107, s. 266-280
-
Tidskriftsartikel (refereegranskat)abstract
- C-peptide therapy protects against diabetic micro- and macrovascular damages and neuropatic complications. However, to date, the role of C-peptide in preventing diabetes-related bone loss has not been investigated. Our aim was to evaluate if C-peptide infusion improves bone quality in diabetic rats. Twenty-three male Wistar rats were randomly divided into three groups: normal control group; sham diabetic control group; diabetic plus C-peptide group. Diabetes was induced by streptozotocin injection and C-peptide was delivered subcutaneously for 6weeks. We performed micro-CT and histological testing to assess several trabecular microarchitectural parameters. At the end, diabetic plus C-peptide rats had a higher serum C-peptide (p=0.02) and calcium (p=0.04) levels and tibia weight (p=0.02) than the diabetic control group. The diabetic plus C-peptide group showed a higher trabecular thickness and cross-sectional thickness than the diabetic control group (p=0.01 and p=0.03). Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison with the diabetic control group (p=0.045 and p=0.034). Diabetic rats receiving C-peptidehad higher quality of trabecular bone than diabetic rats not receiving this treatment. If confirmed, C-peptide could have a role in improving bone quality in diabetes.
|
|
| 2. |
- Mazza, Elisa, et al.
(författare)
-
Bending Resistance at Hip and Fractures Risk in Postmenopausal Women Independent of Bone Mineral Density.
- 2022
-
Ingår i: Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 25:2, s. 198-207
-
Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that aging loss of bone mass is not necessarily associated with reduced mechanical proprieties as bending resistance. Since postmenopausal women with fracture and without osteoporosis might have an impairment in the bending mechanisms at hip, our aim was to assess if women with and without fractures differ in the femoral parameters of resistance to bending, independent of the bone loss. In this cross-sectional study we enrolled 192 postmenopausal women who underwent X-ray absorptiometry scan to measure bone mineral density as well as cross-sectional geometry parameters at the hip (Hip structure analysis). Among women with osteoporosis, a higher odds ratio for fracture was found in the first tertile of NN-Dmax, a parameter linked to the resistance to bending forces in a cross-section (tertile I, OR=6.7, p=0.03; CI 1.19-38.01; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of NN-Dmax (tertile I, OR=6.0, p=0.02; CI 1.26-28.4; reference tertile III). Among women without osteoporosis, a significantly higher odds ratio for fracture was found in thefirst tertile of IT-CSA, a parameter of resistance to axial load (tertile I, OR=7.2, p=0.002; CI 2.04-25.9; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of IT-CSA (OR=18.4, p=0.001; CI 1.52-221.8; tertile III reference). We demonstrate that some hip structural parameters are independently associated to the fracture risk in postmenopausal women.
|
|
| 3. |
- Ferro, Yvelise, et al.
(författare)
-
Protein and vitamin B6 intake are associated with liver steatosis assessed by transient elastography, especially in obese individuals.
- 2017
-
Ingår i: Clinical and molecular hepatology. - : The Korean Association for the Study of the Liver. - 2287-285X .- 2287-2728.
-
Tidskriftsartikel (refereegranskat)abstract
- Although the detrimental effects of several dietary components on the promotion of nonalcoholic fatty liver disease are well known, no studies have assessed the role of dietary vitamin B6. Moreover, studies on the associations between dietary components or body composition indices and liver steatosis assessed by transient elastography are rare. Our aim was to identify the nutritional factors and anthropometric parameters associated with liver steatosis.In this cross-sectional study, we enrolled 168 individuals (35% obese) who underwent a liver steatosis assessment by Controlled Attenuation Parameter measurement and nutritional assessment.Tertiles of vitamin B6 intake were positively associated with hepatic steatosis (B=1.89, P=0.026, confidence interval [CI] 0.03-0.80) as well as with triglycerides, glucose, alanine aminotransferase (ALT), and body mass index . In obese individuals, after multivariable analysis, the Controlled Attenuation Parameter score was still associated with triglycerides, ALT, and total protein intake (B=0.56, P=0.01, CI 0.10-1.02). Participants in tertile I (low intake) had a lower Controlled Attenuation Parameter than those in tertile III (P=0.01).We found a positive association between hepatic steatosis or Controlled Attenuation Parameter score and vitamin B6/total protein intake, probably related to the high intake of meat. Vitamin B6 might have a pathogenic role related to the increase of hepatic steatosis.
|
|
| 4. |
- Lamprinoudi, Theodora, et al.
(författare)
-
The link between nutritional parameters and bone mineral density in women: results of a screening programme for osteoporosis
- 2014
-
Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Background A positive association between handgrip strength and bone mineral density was demonstrated, but not all the investigations confirmed these results. We conducted a screening programme for osteoporosis in a large cohort of postmenopausal women to investigate the relationship between handgrip strength, other nutritional parameters and bone density. Methods This investigation involved 1,300 white volunteers. All participants underwent a bone mineral density evaluation at the heel and a handgrip strength measurement. Results The mean T-score value was -1.15 ± 1; a total of 181 participants reported at least one osteoporotic fracture. In the univariate analysis, both handgrip strength and body mass index were associated with the T-score value. Adjustment for confounding factors confirmed this relationship showing, in the multivariate analysis, that the body mass index was positively correlated to the T-score (B = 0.034; p = 0.001) and, in the logistic regression analysis, that handgrip strength was associated with the presence of osteoporosis (P = 0.005). Conclusion Both body mass index and handgrip strength were strongly correlated to bone mineral density, assessed with ultrasound, suggesting a possible key role as bone disease predictors.
|
|
| 5. |
- Maglio, Cristina, 1983, et al.
(författare)
-
The IRS1 rs2943641 Variant and Risk of Future Cancer Among Morbidly Obese Individuals.
- 2013
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:4
-
Tidskriftsartikel (refereegranskat)abstract
- Context:Obesity and insulin resistance are risk factors for cancer development. The IRS1 rs2943641 genetic variant has been widely associated with insulin resistance.Objective:The aim of the study was to examine whether the IRS1 rs2943641 associates with cancer incidence in obese individuals.Design, Setting and Patients:The IRS1 rs2943641 was genotyped in participants from the Swedish Obese Subjects (SOS) study, an intervention trial on the effect of bariatric surgery on mortality and morbidity compared with usual care and in the population-based Malmö Diet and Cancer (MDC) cohort. In both studies, the median follow-up for cancer incidence was about 15 years.Intervention and Main Outcome Measure:Cancer incidence was assessed in both the SOS and the MDC cohorts through national and local registers.Results:The IRS1 T allele was associated with lower insulin resistance in both the SOS and the MDC studies. A lower cancer incidence was found in T allele carriers from the SOS control group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62-0.96; P = .021) and was restricted to morbidly obese individuals (HR 0.67, 95% CI 0.50-0.91; P = .011). No evidence of such association was detected in the surgery group (interaction P = .005). In the MDC cohort, a nonsignificant tendency for lower cancer incidence in T allele carriers was observed only in morbidly obese individuals. A meta-analysis of morbidly obese individuals (body mass index > 40 kg/m(2)) from the two cohorts strengthened the evidence for the association (HR 0.66, 95% CI 0.50-0.87; P = .004).Conclusions:Our results suggest that the T allele of rs2943641 near IRS1 may associate with lower cancer incidence in morbidly obese individuals.
|
|
| 6. |
- Mancina, Rosellina Margherita, et al.
(författare)
-
COBLL1 rs7607980 genetic variant and insulin resistance in overweight and obese children.
- 2013
-
Ingår i: Diabetes/metabolism research and reviews. - : Wiley. - 1520-7560 .- 1520-7552. ; 29:5, s. 413-6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Childhood obesity is a growing epidemic worldwide and it is associated with metabolic complications, such as insulin resistance. Recently, a genetic variation (rs7607980) in the cordon-bleu protein-like 1 (COBLL1) gene has been associated with lower insulin resistance in adults. The aim of the study was to investigate if the association between COBLL1 rs7607980 genetic variant and lower insulin resistance was present early in life. METHODS: This sequence variant was genotyped in 878 overweight and obese children (mean age: 10years) from Sardinia, Italy, from the outpatient clinic of the Pediatric Endocrine Unit, at the Regional Hospital for Microcitaemia in Cagliari. Insulin resistance was assessed by measurement of fasting circulating insulin levels before and after an oral glucose tolerance test (OGTT) and by homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: The COBLL1 rs7607980 C allele was associated with lower fasting insulin and HOMA-IR levels (P=0.002 and P=0.035, respectively) in overweight and obese children. Importantly, lower insulin levels were also observed two hours after OGTT in C allele carriers (P=0.009). CONCLUSIONS: The present study shows for the first time the association between COBLL1 rs7607980 C allele, lower serum insulin levels and lower insulin resistance in overweight and obese children. Copyright © 2013 John Wiley & Sons, Ltd.
|
|
| 7. |
- Mancina, Rosellina Margherita, et al.
(författare)
-
The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent.
- 2016
-
Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 150:5, s. 1219-1230
-
Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD.
|
|
| 8. |
- Montalcini, Tiziana, et al.
(författare)
-
Carotid and brachial arterial enlargement in postmenopausal women with hypertension.
- 2012
-
Ingår i: Menopause. - : Ovid Technologies (Wolters Kluwer Health). - 1530-0374 .- 1072-3714. ; 19:2, s. 145-149
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: The aim of this study was to test whether systemic hypertension influences brachial and carotid artery remodeling in postmenopausal women. A secondary aim was to evaluate the possible role of pulse pressure. METHODS:: We enrolled 100 postmenopausal women affected by hypertension (cases) and 100 women with blood pressure within the reference range (controls) matched for age and body mass index because the influence of these variables on artery diameter is well known. Clinical and biochemical parameters were also assessed. All women underwent B-mode ultrasonography to measure the carotid and brachial artery diameter. RESULTS:: The case group had significantly larger brachial and common carotid artery diameters than control groups (P < 0.001). This result did not change after correction for confounding variables. Indeed, the women with hypertension had higher glucose and insulin levels and greater carotid atherosclerosis prevalence than did the control population. A multivariate linear regression analysis showed a correlation between artery diameters and hypertension status in the whole population. To evaluate the influence of pulse pressure, each group (cases and controls) was divided into two subgroups, according to the group-specific pulse pressure median. The women with a pulse pressure rate higher than the median value had larger artery diameters compared with those with lower pulse pressure rates in both groups with and without hypertension. CONCLUSIONS:: Hypertension can promote generalized artery enlargement, and pulse pressure also plays a role in artery remodeling. Interestingly, pulse pressure seems to influence arterial diameter in individuals with blood pressure within the reference range. The role of hypertension in artery remodeling behind age and the body mass index requires further investigations on the mechanisms underlying remodeling.
|
|
| 9. |
- Pingitore, Piero, 1986, et al.
(författare)
-
PNPLA3 overexpression results in reduction of proteins predisposing to fibrosis.
- 2016
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:23, s. 5212-5222
-
Tidskriftsartikel (refereegranskat)abstract
- Liver fibrosis is a pathological scarring response to chronic hepatocellular injury and hepatic stellate cells (HSCs) are key players in this process. PNPLA3 I148M is a common variant robustly associated with liver fibrosis but the mechanisms underlying this association are unknown.We aimed to examine a) the effect of fibrogenic and proliferative stimuli on PNPLA3 levels in HSCs and b) the role of wild type and mutant PNPLA3 overexpression on markers of HSC activation and fibrosis.Here we show that PNPLA3 is upregulated by the fibrogenic cytokine transforming growth factor-beta (TGF-β), but not by platelet-derived growth factor (PDGF), and is involved in the TGF-β-induced reduction in lipid droplets in primary human HSCs. Furthermore, we show that retinol release from human HSCs ex vivo is lower in cells with the loss-of-function PNPLA3 148M compared with 148I wild type protein. Stable overexpression of PNPLA3 148I wild type, but not 148M mutant, in human HSCs (LX-2 cells) induces a reduction in the secretion of matrix metallopeptidase 2 (MMP2), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2), which is mediated by retinoid metabolism.In conclusion, we show a role for PNPLA3 in HSC activation in response to fibrogenic stimuli. Moreover, we provide evidence to indicate that PNPLA3-mediated retinol release may protect against liver fibrosis by inducing a specific signature of proteins involved in extracellular matrix remodeling.
|
|
| 10. |
- Pingitore, Piero, 1986, et al.
(författare)
-
Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function.
- 2014
-
Ingår i: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1841:4, s. 574-580
-
Tidskriftsartikel (refereegranskat)abstract
- The patatin-like phospholipase domain containing 3 (PNPLA3, also called adiponutrin, ADPN) is a membrane-bound protein highly expressed in the liver. The genetic variant I148M (rs738409) was found to be associated with progression of chronic liver disease. We aimed to establish a protein purification protocol in a yeast system (Pichia pastoris) and to examine the human PNPLA3 enzymatic activity, substrate specificity and the I148M mutation effect. hPNPLA3 148I wild type and 148M mutant cDNA were cloned into P. pastoris expression vectors. Yeast cells were grown in 3L fermentors. PNPLA3 protein was purified from membrane fractions by Ni-affinity chromatography. Enzymatic activity was assessed using radiolabeled substrates. Both 148I wild type and 148M mutant proteins are localized to the membrane. The wild type protein shows a predominant lipase activity with mild lysophosphatidic acid acyl transferase activity (LPAAT) and the I148M mutation results in a loss of function of both these activities. Our data show that PNPLA3 has a predominant lipase activity and I148M mutation results in a loss of function.
|
|
