Circulating fibroblast growth factor 21 levels are closely associated with hepatic fat content: a cross-sectional study

Background and Aims

Fibroblasts growth factor 21 (FGF21), a liver-secreted endocrine factor involved in regulating glucose and lipid metabolism, has been shown to be elevated in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the quantitative correlation between serum FGF21 level and hepatic fat content.

Methods

A total of 138 subjects (72 male and 66 female) aged from 18 to 65 years with abnormal glucose metabolism and B-ultrasonography diagnosed fatty liver were enrolled in the study. Serum FGF21 levels were determined by an in-house chemiluminescence immunoassay and hepatic fat contents were measured by proton magnetic resonance spectroscopy.

Results

Serum FGF21 increased progressively with the increase of hepatic fat content, but when hepatic fat content increased to the fourth quartile, FGF21 tended to decline. Serum FGF21 concentrations were positively correlated with hepatic fat content especially in subjects with mild/moderate hepatic steatosis (r = 0.276, p = 0.009). Within the range of hepatic steatosis from the first to third quartile, FGF21 was superior to any other traditional clinical markers including ALT to reflect hepatic fat content. When the patients with severe hepatic steatosis (the fourth quartile) were included, the quantitative correlation between FGF21 and hepatic fat content was weakened.

Conclusions

Serum FGF21 was a potential biomarker to reflect the hepatic fat content in patients with mild or moderate NAFLD. In severe NAFLD patients, FGF21 concentration might decrease due to liver inflammation or injury.     

Lower Cerebrospinal Fluid/Plasma Fibroblast Growth Factor 21 (FGF21) Ratios and Placental FGF21 Production in Gestational Diabetes

Objectives

Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants.

Design

CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m²) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m²)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA.

Results

Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05).

Conclusions

The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points.     

Plasma lipids and betaine are related in an acute coronary syndrome cohort

Background

Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these.

Methodology

Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment.

Principal Findings

Plasma betaine negatively correlated with triglyceride (Spearman''s r_s = −0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r_s = −0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin.

Conclusion

Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk.     

Effects of short-term continuous subcutaneous insulin infusion on fasting plasma fibroblast growth factor-21 levels in patients with newly diagnosed type 2 diabetes mellitus

Background

To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma fibroblast growth factor-21 (FGF-21) levels in patients with newly diagnosed type 2 diabetes mellitus (nT2DM).

Method

Sixty-eight patients with nT2DM (nT2DM group), and 52 gender-, age- and body mass index (BMI) -matched normal glucose tolerance (NGT group) controls participated in the study. 30 nT2DM patients with FBG≥14.0 mmol/L were treated with CSII for 2 weeks, and were underwent a euglycemic–hyperinsulinemic clamp pre- and post-treatment. Plasma FGF-21 concentrations were measured with a commercial ELISA kit. The relationship between plasma FGF-21 levels and metabolic parameters was also analyzed.

Results

Fasting plasma FGF-21 levels were higher in the nT2DM group than in NGT groups (1.60±0.08 vs. 1.13±0.26 µg/L, P<0.01). In nT2DM patients, fasting plasma FGF-21 concentrations were significantly decreased after CSII treatment for 2 weeks (1.60±0.08 vs.1.30±0.05 µg/L, P<0.05), accompanied by a significant increase in the whole body glucose uptake (M value) and blood glucose control. The changes in plasma FGF-21 levels (ΔFGF-21) were positively associated with the amelioration of insulin resistance shown by the changes in M value.

Conclusion

Plasma FGF-21 level is associated with whole body insulin sensitivity and significantly reduced following short-term CSII treatment.     

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

Background

We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Methods

In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.

Results

1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).

Conclusions

These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.     

Plasma heme oxygenase-1 concentration in relation to impaired glucose regulation in a non-diabetic Chinese population

Background

Our previous study has recently shown that plasma heme oxygenase-1 (HO-1), a stress-responsive protein, is elevated in individuals with type 2 diabetes. The current study aimed to examine the association between plasma HO-1 concentration and impaired glucose regulation (IGR) in non-diabetic individuals.

Methods

We conducted a case-control study including a total of 865 subjects (262 IGR individuals and 603 healthy controls) in a Chinese population. Basic characteristics were collected by questionnaire and standardized anthropometric measurements. Plasma HO-1 concentration was determined by ELISA.

Results

Plasma HO-1 concentration was significantly increased in IGR individuals compared with healthy controls (1.34 (0.81–2.29) ng/ml vs 0.98 (0.56–1.55) ng/ml, P<0.001). After adjustment for age, sex, and BMI, the ORs for IGR in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 3.42 (95% CI 2.11–5.54; P for trend <0.001). The trend remained significant even after additional adjustment for smoking, alcohol drinking, hypertension, family history of diabetes, lipid profiles and C-reactive protein. In the receiver-operating characteristic curve analysis, addition of plasma HO-1 concentration to a model with known risk factors yielded significantly improved discriminative value for IGR (area under the curves 0.75 (95% CI 0.71–0.78) vs. 0.72 (95% CI 0.69–0.76); P for difference = 0.026).

Conclusions

Elevated plasma HO-1 concentration is significantly associated with increased ORs for IGR. However, its clinical utility should be validated in further studies, especially in prospective cohort studies.     

Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors: a nationwide cohort study in Taiwan

Background

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association.

Methods

We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (n = 1393) and an age-matched control cohort of patients hospitalized for appendectomies (n = 1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors.

Results

There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45–2.60; p<0.001) based on Cox regression and a 1.68-fold greater risk for stroke (95% CI, 1.25–2.25; p = 0.001) based on propensity score. This was still the case for two cohorts younger than 75 years old and without traditional cardiovascular risk factors.

Conclusions

This study of Taiwanese patients indicates that CKD itself is a causal risk factor for stroke beyond the traditional cardiovascular risk factors. Primary CKD patients have higher risk for stroke than the general population and all CKD patients, irrespective of the presence or severity of traditional cardiovascular risk factors, should be made aware of the stroke risk and monitored for stroke prevention.     

UCP-2 and UCP-3 proteins are differentially regulated in pancreatic beta-cells

Background

Increased uncoupling protein-2 (UCP-2) expression has been associated with impaired insulin secretion, whereas UCP-3 protein levels are decreased in the skeleton muscle of type-2 diabetic subjects. In the present studies we hypothesize an opposing effect of glucose on the regulation of UCP-2 and UCP-3 in pancreatic islets.

Methodology

Dominant negative UCP-2 and wild type UCP-3 adenoviruses were generated, and insulin release by transduced human islets was measured. UCP-2 and UCP-3 mRNA levels were determined using quantitative PCR. UCP-2 and UCP-3 protein expression was investigated in human islets cultured in the presence of different glucose concentrations. Human pancreatic sections were analyzed for subcellular localization of UCP-3 using immunohistochemistry.

Principal Findings

Dominant negative UCP-2 expression in human islets increased insulin secretion compared to control islets (p<0.05). UCP-3 mRNA is expressed in human islets, but the relative abundance of UCP-2 mRNA was 8.1-fold higher (p<0.05). Immunohistochemical analysis confirmed co-localization of UCP-3 protein with mitochondria in human beta-cells. UCP-2 protein expression in human islets was increased ∼2-fold after high glucose exposure, whereas UCP-3 protein expression was decreased by ∼40% (p<0.05). UCP-3 overexpression improved glucose-stimulated insulin secretion.

Conclusions

UCP-2 and UCP-3 may have distinct roles in regulating beta-cell function. Increased expression of UCP-2 and decreased expression of UCP-3 in humans with chronic hyperglycemia may contribute to impaired glucose-stimulated insulin secretion. These data imply that mechanisms that suppress UCP-2 or mechanisms that increase UCP-3 expression and/or function are potential therapeutic targets to offset defects of insulin secretion in humans with type-2 diabetes.     

Protective Roles of DMP1 in High Phosphate Homeostasis

Purpose

Dmp1 (dentin matrix protein1) null mice (Dmp1^−/−) display hypophosphatemic rickets with a sharp increase in fibroblast growth factor 23 (FGF23). Disruption of Klotho (the obligatory co-receptor of FGF23) results in hyperphosphatemia with ectopic calcifications formed in blood vessels and kidneys. To determine the role of DMP1 in both a hyperphosphatemic environment and within the ectopic calcifications, we created Dmp1/Klotho compound deficient (Dmp1^−/−kl/kl) mice.

Procedures

A combination of TUNEL, immunohistochemistry, TRAP, von Kossa, micro CT, bone histomorphometry, serum biochemistry and Scanning Electron Microscopy techniques were used to analyze the changes in blood vessels, kidney and bone for wild type control, Dmp1^−/−, Klotho deficient (kl/kl) and Dmp1^−/−kl/kl animals.

Findings

Interestingly, Dmp1^−/−kl/kl mice show a dramatic improvement of rickets and an identical serum biochemical phenotype to kl/kl mice (extremely high FGF23, hyperphosphatemia and reduced parathyroid hormone (PTH) levels). Unexpectedly, Dmp1^−/−kl/kl mice presented elevated levels of apoptosis in osteocytes, endothelial and vascular smooth muscle cells in small and large blood vessels, and within the kidney as well as dramatic increase in ectopic calcification in all these tissues, as compared to kl/kl.

Conclusion

These findings suggest that DMP1 has an anti-apoptotic role in hyperphosphatemia. Discovering this novel protective role of DMP1 may have clinical relevance in protecting the cells from apoptosis in high-phosphate environments as observed in chronic kidney disease (CKD).     

Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory.

Results

LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005).

Conclusion

In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.     

Effect of temperature on cystic fibrosis lung disease and infections: a replicated cohort study

Background

Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF). Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown.

Methods

Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378). Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439), the Australian CF Data Registry (ACFDR: n = 1801), and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167).

Results

In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001) was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001), ACFDR (1.05; p = 0.002), and ACFBAL (1.09; p = 0.003) subjects. Warmer temperatures (−0.34 points per °F; p = 0.005) and public insurance (−6.43 points; p<0.001) were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: −0.31; p<0.001; insurance: −9.11; p<0.001) and similar in the ACFDR subjects (temperature: −0.23; p = 0.057). The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function.

Conclusions

Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents.     

Areca users in combination with tobacco and alcohol use are associated with younger age of diagnosed esophageal cancer in Taiwanese men

Background

Whether the habitual use of substances (tobacco, alcohol, or areca nut (seed of the Areca palm)) can affect the age of esophageal squamous cell carcinoma (ESCC) presentation has rarely been examined.

Methods

The study subjects were those who were males and the first time to be diagnosed as ESCC (ICD-9 150) and who visited any of three medical centers in Taiwan between 2000 and 2009. A standardized questionnaire was used to collect substance uses and other variables.

Results

Mean age (±SD) at presentation of ESCC was 59.2 (±11.3) years in a total of 668 cases. After adjusting for other covariates, alcohol drinkers were 3.58 years younger to have ESCC than non-drinkers (p = 0.002). A similar result was found among areca chewers, who were 6.34 years younger to have ESCC than non-chewers (p<0.0001), but not among cigarette smokers (p = 0.10). When compared to the group using 0–1 substances, subjects using both cigarettes and alcohol were nearly 3 years younger to contract ESCC. Furthermore, those who use areca plus another substance were 7–8 years younger. Subjects using all three substances had the greatest age difference, 9.20 years younger (p<0.0001), compared to the comparison group.

Conclusion

Our findings suggest that habitually consuming tobacco, alcohol, and areca nut can influence the age-onset of ESCC. Since the development of ESCC is insidious and life-threatening, our observation is worthy to be reconfirmed in the large-scale and long-term follow-up prospective cohort studies to recommend the screening strategy of this disease.     

Polymorphisms in the SAA1/2 gene are associated with carotid intima media thickness in healthy Han Chinese subjects: the Cardiovascular Risk Survey

Background

Serum amyloid A protein (SAA) is not only an inflammatory factor, but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein (HDL), which has been linked to atherosclerosis. However, the relationship between genetic polymorphisms of SAA and the intima-media thickness (IMT) of the common carotid artery in healthy subjects remains unclear. We investigated the role of SAA1 and SAA2 gene polymorphisms with IMT in a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study.

Methodology/Principal Findings

Anthropometric and B-mode ultrasound of the carotid IMT were measured in 1914 subjects (849 men; 1065 women) recruited from seven cities in Xinjiang province, (western China). Four SNPs (rs12218, rs2229338, rs1059559, and rs2468844) were genotyped by use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The SNP rs12218 was associated with carotid IMT by analyses of a dominate model (P<0.001) and additive model (P = 0.003), and the difference remained significant after multivariate adjustment (P = 0.008, P<0.001, respectively). This relationship was also observed in rs2468844 after multivariate adjustment by recessive model analysis (P = 0.011) but this was not observed in rs2229338 and rs1059559 before and after multivariate adjustment. These associations were not modified by serum HDL concentration. Furthermore, there were significant interactions between rs2468844 and rs12218 (interaction P<0.001) and rs2229338 (interaction P = 0.001) on carotid IMT.

Conclusion/Significance

Both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects.     

Serum CXCL16 as a Novel Marker of Renal Injury in Type 2 Diabetes Mellitus

Background

Soluble C-X-C chemokine ligand 16 (CXCL16), a scavenger receptor for oxidized low density lipoprotein, has been shown to promote atherogenic effects in vivo and to predict long-term mortality in acute coronary syndrome. The aim of this study was to explore the association of circulating CXCL16 levels with diabetic subjects with and without renal disease.

Methodology/Principal Findings

One hundred twenty Chinese subjects, which included patients with type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and CKD, as well as healthy controls, were enrolled in this study. Serum CXCL16 levels were examined by immunoassay and other clinical biochemical parameters were tested based on standard methods. Our results indicated that, HDL and LDL cholesterol levels are significantly different in DN but not in T2D patients in comparison with healthy subjects. On the other hand, Serum CXCL16 levels were significantly increased in DN subjects compared with age and gender matched healthy and T2DM subjects (p<0.05 respectively). However, no significant changes in serum CXCL16 levels were found between T2DM and healthy subjects. Furthermore, serum CXCL16 concentration negatively correlated with estimated glomerular filtrate rate, creatinine clearance rate and blood albumin, and positively with 24 h proteinuria, blood urea nitrogen (BUN), creatinine, and uric acid after adjusting for age, gender and BMI in subjects with DN. Multiple stepwise regression analyses indicated that serum CXCL16 levels were independently associated with serum 24 h proteinuria, and BUN (p<0.05 respectively).

Conclusion

Serum CXCL16 may be an indicator of renal injury in subjects with T2DM. Understanding the exact mechanism of elevated CXCL16 in subjects with DN requires further study.     

Iliopsoas and gluteal muscles are asymmetric in tennis players but not in soccer players

Purpose

To determine the volume and degree of asymmetry of iliopsoas (IL) and gluteal muscles (GL) in tennis and soccer players.

Methods

IL and GL volumes were determined using magnetic resonance imaging (MRI) in male professional tennis (TP) and soccer players (SP), and in non-active control subjects (CG) (n = 8, 15 and 6, respectively).

Results

The dominant and non-dominant IL were hypertrophied in TP (24 and 36%, respectively, P<0.05) and SP (32 and 35%, respectively, P<0.05). In TP the asymmetric hypertrophy of IL (13% greater volume in the non-dominant than in the dominant IL, P<0.01) reversed the side-to-side relationship observed in CG (4% greater volume in the dominant than in the contralateral IL, P<0.01), whilst soccer players had similar volumes in both sides (P = 0.87). The degree of side-to-side asymmetry decreased linearly from the first lumbar disc to the pubic symphysis in TP (r = −0.97, P<0.001), SP (r = −0.85, P<0.01) and CG (r = −0.76, P<0.05). The slope of the relationship was lower in SP due to a greater hypertrophy of the proximal segments of the dominant IL. Soccer and CG had similar GL volumes in both sides (P = 0.11 and P = 0.19, for the dominant and contralateral GL, respectively). GL was asymmetrically hypertrophied in TP. The non-dominant GL volume was 20% greater in TP than in CG (P<0.05), whilst TP and CG had similar dominant GL volumes (P = 0.14).

Conclusions

Tennis elicits an asymmetric hypertrophy of IL and reverses the normal dominant-to-non-dominant balance observed in non-active controls, while soccer is associated to a symmetric hypertrophy of IL. Gluteal muscles are asymmetrically hypertrophied in TP, while SP display a similar size to that observed in controls. It remains to be determined whether the different patterns of IL and GL hypertrophy may influence the risk of injury.     

The evaluation of the oxidative stress parameters in patients with primary angle-closure glaucoma

Objective

To clarify the presence of oxidative stress in patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between oxidative stress and PACG.

Methods

Fifty patients with primary angle-closure glaucoma and fifty healthy controls of matched age and gender were included in the study prospectively. Serum samples were obtained to detect the oxidation degradation products malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), advanced oxidation protein products (AOPP), protein carbonyl (PC), ischemia-modified albumin (IMA) and 8-hydroxydeoxyguanosin (8-OHdG).

Results

The concentration of MDA and CD in PACG patients was significantly higher than those of the control subjects (P<0.05, P<0.01). The serum 4-HNE concentrations were increased in PACG patients, but the differences with those of the healthy controls were not statistically significant. Compared to normal subjects, there was significant higher in serum AOPP and PC in PACG patients (P<0.01). PACG patients had higher levels of 8-OHdG in serum with respect to the comparative group of normal subjects (P<0.01). When plasma IMA levels in the PACG group were compared with those in the control group, significant increases in IMA were observed in the former (P<0.05).

Conclusions

Our study demonstrated that IMA is a new biomarker available for assessing oxidative stress in PCAG. Oxidative stress is an important risk factor in the development of primary angle-closure glaucoma. Increased levels of oxidative stress products may be associated with primary angle-closure glaucoma.     

Intraduodenal administration of intact pea protein effectively reduces food intake in both lean and obese male subjects

Background

Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects.

Methods

Ten lean (BMI:23.0±0.7 kg/m²) and ten obese (BMI:33.4±1.4 kg/m²) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded.

Results

CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA.

Conclusions

Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity.     

Patterns of Circulating Fibroblast Growth Factor 21 in Subjects with and without Type 2 Diabetes

Background

Fibroblast growth factor 21 (FGF21) exerts wide-range effects on carbohydrate and lipid metabolism. However, its perturbation in type 2 diabetes mellitus (T2DM) remains elusive. Besides, previous human studies in T2DM simply investigated fasting or stimulated levels of FGF21. The current study sought to evaluate the temporal changes of circulating FGF21 in subjects with and without T2DM.

Methods

Ten patients with T2DM and 16 normal controls (NC) were recruited. Participants were categorized as obese (BMI≥25 kg/m²) or lean (BMI<25 kg/m²). Blood samples were drawn every 30 min within 7 hours (8 a.m.-3 p.m.). Serum FGF21, blood glucose, insulin, free fatty acids (FFAs) and adiponectin were measured in all subjects.

Results

The peak levels of FGF21 were observed in the fasting state (8 a.m.) both in T2DM and NC groups (267.35 ±158.72 ng/L vs. 178.93±121.37 ng/L, P = 0.096). FGF21 AUC did not differ significantly between the two groups (T2DM: 949.4±471.47 ng/L; NC: 883.13±561.40 ng/L, P = 0.770). Obese subjects had higher FGF21 levels than lean ones in patients either with or without T2DM. The pattern of FFAs closely resembled that of FGF21. Correlation analysis showed that temporal levels of FGF21 were significantly related to FFAs (r = 0.749, P = 0.002),but not blood glucose, insulin or adiponectin (all P> 0.05).

Conclusions

These findings suggest that the pattern of circulating FGF21 does not differ significantly between T2DM and NC,although T2DM patients showed a trend toward higher fasting FGF21 than healthy subjects. The pattern of circulating FFAs is significantly associated with that of FGF21.     

Two recessive mutations in FGF5 are associated with the long-hair phenotype in donkeys

Background

Seven donkey breeds are recognized by the French studbook. Individuals from the Pyrenean, Provence, Berry Black, Normand, Cotentin and Bourbonnais breeds are characterized by a short coat, while those from the Poitou breed (Baudet du Poitou) are characterized by a long-hair phenotype. We hypothesized that loss-of-function mutations in the FGF5 (fibroblast growth factor 5) gene, which are associated with a long-hair phenotype in several mammalian species, may account for the special coat feature of Poitou donkeys. To the best of our knowledge, mutations in FGF5 have never been described in Equidae.

Methods

We sequenced the FGF5 gene from 35 long-haired Poitou donkeys, as well as from a panel of 67 short-haired donkeys from the six other French breeds and 131 short-haired ponies and horses.

Results

We identified a recessive c.433_434delAT frameshift deletion in FGF5, present in Poitou and three other donkey breeds and a recessive nonsense c.245G > A substitution, present in Poitou and four other donkey breeds. The frameshift deletion was associated with the long-hair phenotype in Poitou donkeys when present in two copies (n = 31) or combined with the nonsense mutation (n = 4). The frameshift deletion led to a stop codon at position 159 whereas the nonsense mutation led to a stop codon at position 82 in the FGF5 protein. In silico, the two truncated FGF5 proteins were predicted to lack the critical β strands involved in the interaction between FGF5 and its receptor, a mandatory step to inhibit hair growth.

Conclusions

Our results highlight the allelic heterogeneity of the long-hair phenotype in donkeys and enlarge the panel of recessive FGF5 loss-of-function alleles described in mammals. Thanks to the DNA test developed in this study, breeders of non-Poitou breeds will have the opportunity to identify long-hair carriers in their breeding stocks.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-014-0065-5) contains supplementary material, which is available to authorized users.