Serum hemorphin‐7 levels are decreased in obesity

Objective:

Hemorphin peptides exhibit biological activities that interfere with the endorphin system, the inflammatory response, and blood‐pressure control. VV‐hemorphin‐7 and LVV‐hemorphin‐7 peptides exert a hypotensive effect, in particular, by inhibiting the renin–angiotensin system. Furthermore, levels of circulating hemorphin‐7 peptides have been found to be decreased in diseases such as type 1 and type 2 diabetes.

Design and Methods:

Because type 2 diabetes and obesity share common features, such as insulin resistance, microinflammation, high glomerular‐filtration rate (GFR), and cardiovascular risk, we evaluated serum VV‐hemorphin‐7 like immunoreactivity (VVH7‐i.r.) levels, using an enzyme‐linked immunosorbent assay method, on a group of 54 obese subjects without diabetes or hypertension, compared with a group of 33 healthy normal‐weight subjects.

Results:

Circulating VVH7‐i.r. levels were significantly decreased in the obese group compared with the control group (1.98 ± 0.19 vs. 4.86 ± 0.54 µmol/l, respectively, P < 0.01), and a significant negative correlation between VVH7‐i.r. and diastolic blood pressure (DBP) was found in obese patients (r = ?0.35, P = 0.011). There was no significant correlation between VVH7‐i.r. level and insulin resistance, metabolic syndrome, or GFR.

Conclusions:

The decreased serum hemorphin‐7 found in obese subjects, as in diabetes, may contribute to the development of hypertension and to the cardiovascular risk associated with these metabolic diseases.

     

Acquired liver fat is a key determinant of serum lipid alterations in healthy monozygotic twins

Objective: The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI‐discordant monozygotic (MZ) twin pairs were studied. Design and Methods: Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel‐electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI‐discordant (within‐pair difference [Δ] in BMI >3 kg/m²) and nin concordant (ΔBMI <3 kg/m²) MZ twin pairs, identified from two nationwide cohorts of Finnish twins. Results: Despite a strong similarity of MZ twins in lipid parameters (intra‐class correlations 0.42‐0.90, P < 0.05), concentrations of apolipoprotein B (ApoB), intermediate‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein 3a% (HDL3a%), and HDL3c% were higher (P < 0.05) and those of HDL cholesterol, HDL2‐C, and HDL2b% were lower (P < 0.01) in the heavier co‐twins of BMI‐discordant pairs. The composition of lipoprotein particles was similar in the co‐twins. When BMI‐discordant pairs were further divided into liver fat‐discordant and concordant (based on median for Δliver fat, 2.6%), the adverse lipid profile was only seen in those heavy co‐twins who also had high liver fat. Conversely, BMI‐discordant pairs concordant for liver fat did not differ significantly in lipid parameters. In multivariate analyses controlling for Δsubcutaneous, Δintra‐abdominal fat, sex, Δsmoking and Δphysical activity, Δliver fat was the only independent variable explaining the variation in ΔApoB, Δtotal cholesterol, and ΔLDL‐C concentration. Conclusions: Several pro‐atherogenic changes in the amounts of lipids but not in the composition of lipoprotein particles were observed in acquired obesity. In particular, accumulation of liver fat was associated with lipid disturbances, independent of genetic effects.     

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans

Objective:

To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short‐term overfeeding in healthy subjects.

Design and methods:

The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6‐7 days on a weight‐maintenance diet (control, C; n = 55) and 6‐7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10).

Results:

F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI.

Conclusions:

Short‐term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short‐term regulation of hepatic glucose metabolism by simple carbohydrates.     

Effects of Feed Supplementation on Mineral Composition,Mechanical Properties and Structure in Femurs of Iberian Red Deer Hinds (Cervus elaphus hispanicus)

Few studies in wild animals have assessed changes in mineral profile in long bones and their implications for mechanical properties. We examined the effect of two diets differing in mineral content on the composition and mechanical properties of femora from two groups each with 13 free-ranging red deer hinds. Contents of Ca, P, Mg, K, Na, S, Cu, Fe, Mn, Se, Zn, B and Sr, Young’s modulus of elasticity (E), bending strength and work of fracture were assessed in the proximal part of the diaphysis (PD) and the mid-diaphysis (MD). Whole body measures were also recorded on the hinds. Compared to animals on control diets, those on supplemented diets increased live weight by 6.5 kg and their kidney fat index (KFI), but not carcass weight, body or organ size, femur size or cortical thickness. Supplemental feeding increased Mn content of bone by 23%, Cu by 9% and Zn by 6%. These differences showed a mean fourfold greater content of these minerals in supplemental diet, whereas femora did not reflect a 5.4 times greater content of major minerals (Na and P) in the diet. Lower content of B and Sr in supplemented diet also reduced femur B by 14% and Sr by 5%. There was a subtle effect of diet only on E and none on other mechanical properties. Thus, greater availability of microminerals but not major minerals in the diet is reflected in bone composition even before marked body effects, bone macro-structure or its mechanical properties are affected.     

Effects of Late Administration of Pentoxifylline and Tocotrienols in an Image-Guided Rat Model of Localized Heart Irradiation

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.     

Incomplete Normalization of Regulatory T-Cell Frequency in the Gut Mucosa of Colombian HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

Introduction

To evaluate the effect of late initiation of HAART and poor immune reconstitution on the frequency of regulatory T-cells (Treg) in the peripheral blood and gut of HIV-infected patients, we studied Colombian HIV-infected patients who had been on suppressive HAART for at least one year. They had undetectable viremia but were either immunological responders (HIR); (CD4 counts >500 cells/µl) or non-immunological responders (NIR); (CD4 T-cell count <300 cells/µl). Untreated HIV-infected patients and uninfected controls from the same region were also evaluated.

Methods

Frequency and phenotype of regulatory T-cells (Treg) were analyzed in gut biopsies and blood samples. The functional effect of Treg depletion on CMV and HIV responses was determined. Markers of immune activation and circulating LPS levels were quantified.

Results

Untreated patients exhibited high Treg frequency in PBMC and gut, and their Treg express high levels of CTLA-4 and PD-1. Although HAART significantly decreased mucosal Treg frequency, it did not normalize it in any of the treated groups (HIR and NIR patients). Treg normalization was observed in the blood of HIR patients following HAART, but did not occur in NIR patients. Treg from HIV-infected patients (treated or not) suppressed HIV and hCMV-specific T-cells from gut and blood. Plasma LPS levels and percentage of HLA-DR+CD38+ T-cells were significantly elevated in all infected groups compared to controls.

Conclusions

These findings suggest that control of viral replication is not sufficient to normalize gut Treg frequency in patients, independent of their response to HAART. Furthermore, persistence of functional Treg in the gut appears to be associated with the failure of HAART to repair mucosal damage.