Is visfatin an adipokine or myokine? Evidence for greater visfatin expression in skeletal muscle than visceral fat in chickens

Visfatin, an adipokine hormone produced primarily by visceral adipose tissue in mammals, has been implicated in the immune system, cellular aging, and glucose metabolism. Increased visceral adiposity and hyperglycemia have been correlated with elevated plasma visfatin levels in humans. The present study investigated visfatin cDNA and protein expression as well as plasma visfatin levels in chickens that are selected for rapid growth and are naturally hyperglycemic relative to mammals. By RT-PCR, we detected visfatin cDNA in multiple tissues in the chicken. The deduced amino acid sequence of full-length chicken visfatin was 92-93% homologous to mammalian visfatin. Using real-time quantitative PCR and Western blotting, chicken skeletal muscle was found to contain 5- and 3-fold greater quantities of visfatin mRNA and protein than abdominal fat pad, respectively. Visfatin mRNA and protein quantities were not significantly different among sc and visceral adipose tissue depots. Skeletal muscle visfatin mRNA and protein quantities as well as plasma visfatin levels determined by enzyme immunoassay were significantly higher in 8-wk-old compared with 4-wk-old chickens, possibly due to rapid skeletal muscle growth and visceral fat accretion occurring in broiler chickens during this period. However, fasting and refeeding did not affect plasma visfatin levels in the chicken. Collectively, our results provide novel evidence that skeletal muscle, not the visceral adipose tissue, is the primary source of visfatin in chickens, thereby raising the possibility that visfatin may be acting as a myokine affecting skeletal muscle growth and metabolism.     

Exercise blood pressure and the risk of incident cardiovascular disease (from the Framingham Heart Study)

Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p <0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group.     

Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study

OBJECTIVE: To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women. DESIGN: In 1780 unrelated members of the community-based Framingham Heart Study offspring cohort, systolic blood pressure and diastolic blood pressure were measured over a total of six examination cycles encompassing 24 years of follow-up. Multivariate regression analyses were used to assess the relation between untreated cross-sectional and longitudinal blood pressure and polymorphisms at the estrogen receptor-alpha (ESR1), estrogen receptor-beta (ESR2), aromatase (CYP19A1), and nuclear receptor coactivator 1 (NCOA1) genes after adjustment for common risk factors. RESULTS: In men, systolic blood pressure and pulse pressure (systolic blood pressure minus diastolic blood pressure) were associated with two polymorphisms in ESR1, while pulse pressure was also associated with variations in NCOA1 and CYP19A1. Polymorphisms in ESR1, CYP19A1, and NCOA1 were associated with diastolic blood pressure in women. CONCLUSIONS: Although the underlying relations between genes involved in estrogen action and hypertension remain to be completely understood, our findings provide suggestive evidence of gender-specific contributions of estrogen-related genes to blood pressure variation. As no correction for multiple testing was performed in the analyses, we view these results as suggestive and not definitive. Further studies are warranted to confirm these results using a comprehensive set of polymorphisms in order to shed more light on the involvement of estrogen in blood pressure regulation.     

Pancreatic B-cell function in relation to diabetic retinopathy in Asian Indian NIDDM patients

Summary Pancreatic B-cell function in relation to diabetic retinopathy was studied in 195 NIDDM patients with long-standing diabetes. Background diabetic retinopathy (BDR) was present in 95 (48.7%) and proliferative retinopathy (PDR) in 17 (8.7%) of the subjects. There was no significant difference between the BDR, PDR, and non-retinopathy groups with respect to age, age at diagnosis of diabetes and HbA₁ values. Mean duration of diabetes was higher in the PDR group (p<0.05). Serum C-peptide values showed no correlation with the presence of retinopathy or with the duration of diabetes. The C-peptide values were widely scattered in patients with BDR and PDR showing no association between pancreatic B-cell reserve and occurrence or severity of retinopathy in NIDDM patients. Thus, decreased pancreatic B-cell reserve does not appear to be a risk factor for diabetic retinopathy in NIDDM patients.     

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson’s disease in resource constrained setting

Background

Experience with zinc in treating symptomatic hepatic Wilson’s disease (WD) is limited.

Aim

To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson’s disease.

Methods

We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child’s, model for end-stage liver disease (MELD), Nazer’s, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points—baseline at presentation, at transition from penicillamine to zinc and at end of follow up.

Results

Thirty-one patients (median age 11 [5–24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child’s class A, five to Child’s B, and 17 to Child’s C. Duration of initial penicillamine chelation therapy was 134 (2–320) weeks, and of subsequent zinc therapy was 363 (35–728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child’s, MELD, Nazer’s, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2–20) years. Fifteen of the 17 Child’s C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up.

Conclusions

Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

     

Low risk threshold for acquired diabetogenic factors in Asian Indians

India is facing an epidemic of type 2 diabetes, with high prevalence in urban areas. Urbanisation and associated life style changes adversely affect the risk factors for diabetes unmasking the high genetic tendency existing in the population. Various epidemiological studies in Indians have shown that the increasing prevalence of diabetes could be attributed to a high genetic risk and lower risk thresholds for acquired risk factors such as age, obesity, abdominal adiposity and a high percentage of body fat. Diabetes occurs at a younger age in Indians compared to Whites. The risk of diabetes increases with a body mass index (BMI) of >23 kg/m(2) and waist circumference of 85 cm for men and 80 cm for women in Asian Indians. For a given BMI, Asian Indians have higher central adiposity. There is also evidence of higher insulin resistance amongst Indians, and this is partly explained by higher body fat percentage. A large proportion of urban adults has the metabolic syndrome also which predisposes them to both diabetes and cardiovascular diseases. Recognition of these conditions and institution of early preventive measures are urgently needed.     

Chemical and biological characterization of salmon melanocyte-stimulating hormones

Ten peptides related to melanocyto-stimulating hormone (MSH) have been identified in an acid acetone extract of the chum salmon pituitary. All these peptides are related to the alpha-MSH and beta-MSH families, but no peptide related to gamma-MSH has been found. This result is in accordance with the finding that the gamma-MSH segment is deleted from the N-terminal peptide of salmon pro-opiocortin (NPP I). Based on the structures of newly isolated peptides, the maturation process of MSH is discussed. The major components of salmon MSH were tested for biological activities. In the lipolytic assay with rabbit fat cells, alpha-MSH I and alpha-MSH II were equipotent, but beta-MSH I and NPP I exhibited very low or no activity. On the other hand, the des-acetyl-alpha-MSH I was found to be four times as potent as alpha-MSH I in this assay. The steroidogenic activities of alpha-MSH I and N-des-acetyl-alpha-MSH I were approximately 0.05% of the potency of ovine ACTH. All other peptides exhibited less than 0.01% potency. Salmon alpha-MSHs were found to be somewhat more potent melanophore-stimulating agents than the beta-MSHs.