Mihaela Jurdana

Serum bilirubin levels are lower in overweight asymptomatic middle-aged adults: An early indicator of metabolic syndrome?

OBJECTIVE Low levels of bilirubin have recently been associated with obesity, diabetes mellitus, and metabolic syndrome. Here, we hypothesized that serum bilirubin levels might be already altered in overweight asymptomatic middle-aged individuals before full development of the metabolic syndrome. METHODS Healthy nonsmoking adults aged 25-49 (64 women and 32 men) participated in this cross-sectional study. All participants who reported stable weight within the last three months underwent standard anthropomorphological measurements of body composition, blood pressure measurements, aerobic and anaerobic capabilities assessment, dietary intake evaluation, and fasting serological measurements of total and direct bilirubin, glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein. Participants were divided into normal-weight and overweight groups. Linear correlation and multiple regression analyses were used to examine the association of serum bilirubin levels with all metabolic syndrome risk factor changes. RESULTS Serum bilirubin levels were lower in overweight healthy individuals of both sexes, and were negatively associated with abdominal obesity, insulin resistance, fasting glucose, fasting insulin, fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein levels but positively associated with aerobic body capabilities. CONCLUSION Our findings suggest that serum bilirubin levels have the potential to be employed as an early biomarker for indicating asymptomatic individuals at increased risk of developing metabolic syndrome.

Effects of inactivity on human muscle glutathione synthesis by a double‐tracer and single‐biopsy approach

Oxidative stress is often associated to inactivity‐mediated skeletal muscle atrophy. Glutathione is one of the major antioxidant systems stimulated, both at muscular and systemic level, by activation of oxidative processes. We measured changes in glutathione availability, oxidative stress induction and the extent of atrophy mediated by 35 days of experimental bed rest in vastus lateralis muscle of healthy human volunteers. To assess muscle glutathione synthesis, we applied a novel single‐biopsy and double‐tracer ([2H2]glycine and [15N]glycine) approach based on evaluation of steady‐state precursor incorporation in product. The correlations between the traditional (multiple‐samples, one‐tracer) and new (one‐sample, double‐tracer infusion) methods were analysed in erythrocytes by Passing–Bablok and Altman–Bland tests. Muscle glutathione absolute synthesis rate increased following bed rest from 5.5 ± 1.1 to 11.0 ± 1.5 mmol (kg wet tissue)−1 day−1 (mean ±s.e.m.; n= 9; P= 0.02) while glutathione concentration failed to change significantly. Bed rest induced vastus lateralis muscle atrophy, as assessed by pennation angle changes measured by ultrasonography (from 18.6 ± 1.0 to 15.3 ± 0.9 deg; P= 0.01) and thickness changes (from 2.3 ± 0.2 to 1.9 ± 0.1 cm; P < 0.001). Moreover, bed rest increased protein oxidative stress, as measured by muscle protein carbonylation changes (from 0.6 ± 0.1 to 1.00 ± 0.1 Oxydized‐to‐total protein ratio; P < 0.04). In conclusion, we developed in erythrocytes a new minimally invasive method to determine peptide synthesis rate in human tissues. Application of the new method to skeletal muscle suggests that disuse atrophy is associated to oxidative stress induction as well as to compensatory activation of the glutathione system.

Inverse relationship between "a body shape index" (ABSI) and fat-free mass in women and men: Insights into mechanisms of sarcopenic obesity.

BACKGROUND & AIMS Sarcopenic obesity may be defined by a high fat to fat-free mass (FM/FFM) ratio. Skeletal muscle may be negatively influenced by the pro-inflammatory milieu associated with visceral fat, while the loading effect induced by a heavier body mass index (BMI) may enhance muscle anabolism. Recently, a new anthropometric measure based on waist circumference (A Body Shape Index, ABSI) was developed. In this study we have assessed the predictive power of ABSI on the FFM index (FFMI), a surrogate marker of lean mass. METHODS Standard anthropometric parameters and ABSI as well as body composition data (fat and fat-free mass determined by bioelectrical impedance analysis) were assessed in 111 female and 89 male overweight/obese subjects, with no clinically significant co-morbidities. Groups with higher- or lower-ABSI were identified according to median values of this index. RESULTS In women and men, ABSI did not correlate with BMI, while multiple linear regression indicated that BMI (β-coefficients: 0.62 and 0.77, respectively) and ABSI (β-coefficients: -0.26 and -0.22, respectively) independently predicted FFMI (multiple R: 0.72 and 0.83, respectively, P < 0.001). Men and women with lower-ABSI exhibited significantly greater FFMI than the higher-ABSI groups for comparable values of BMI. In men, ABSI was correlated positively with C-reactive protein (CRP) (R = 0.30; P < 0.05) and negatively with the reciprocal of insulin (R = 0.28; P < 0.05), an index of insulin sensitivity. FM/FFM ratio significantly (P < 0.01) correlated with CRP (R = 0.31) in women only. CONCLUSIONS ABSI, a recently introduced marker of abdominal adiposity, may contribute to define the risk of sarcopenia in overweight/obese individuals.

Elevated Serum Levels of Cysteine and Tyrosine: Early Biomarkers in Asymptomatic Adults at Increased Risk of Developing Metabolic Syndrome

As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS) components in subjects prior to the onset of insulin resistance (IR). Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.

Radiation effects on skeletal muscle

Radiation effects on skeletal muscle Background. Adult skeletal muscle is considered resistant to ionizing radiation unless higher doses of radiation are applied; a fact that is attributed to the low number of radiosensitive proliferating cells in adulthood. However, developing skeletal muscles are highly sensitive to ionizing radiation, thus radiotherapy in childhood may induce muscular atrophy. Radiation affects muscle satellite cells by impairing their activation, proliferation and differentiation, as well as neuromuscular junction, by influencing the ionic membrane permeability affecting the Na+/K+ pump. It also prevents muscle growth during development and after injury. Conclusions. The results of the investigation performed after radiation point to the occurrence of a significant change in muscle satellite cell activity. Inhibitors of some proteins such as cytokines in muscle satellite cells could provide a therapeutic benefit in diseases for which muscle mass is limiting, improve response to cancer therapy, and increase life span in patients with cachexia.

Hyperhomocysteinemia and the role of B vitamins in cancer

Hyperhomocysteinemia and the role of B vitamins in cancer Background. Patients suffering from malignancies have increased complications due to corresponding cardiovascular diseases and risk factor for the development of venous thromboembolism. Epidemiological studies have shown that increased homocysteine plasma concentration (hyperhomocysteinemia) is related to a higher risk of coronary heart disease, stroke, peripheral vascular disease and malignancies. Homocysteine (tHcy) is an intermediate sulfurcontaining amino acid produced from methionine during processing of dietary proteins. The plasma homocysteine levels are strongly influenced by diet, as well as by genetic factors. Folic acid, vitamins B6 and B12 are dietary components which influence the plasma homocysteine levels the most. Several studies have found that high blood levels of B vitamins are related to the integrity and function of DNA, and, are at least related to lower concentration of homocysteine. Folate depletion has been found to change DNA methylation and DNA synthesis in both animal and human studies. Because of this critical role of folate, most studies including homocysteine have focused on these two actions. Conclusions. Hyperhomocysteinemia proves to be the most common condition highly associated with both venous and arterial thrombosis in many cancer patients, while the associated pathophysiology has not been precisely established yet. Therefore, of current interest is the possible role of folate metabolism developing into a cancer initiating hyperhomocysteinemia. This review will discuss this possibility.

Hyperhomocysteinemia: Relation to Cardiovascular Disease and Venous Thromboembolism

Homocysteine is a sulphur-containing amino acid, which structurally is closely related to the essential amino acids methionine and cysteine. The cellular methylation cycle performs the metabolism of methionine and since homocysteine is an intermediate within this cycle, the body in this way is provided with all organic homocysteine. The term homocysteine is used to define the combined pool of homocysteine, homocystine, and mixed disulfide compounds (Fig. 1) even involving homocysteine thiolactone a cyclic form which is often found in the plasma of patients with hyperhomocisteinemia.

Total Serum Antioxidant Capacity in Healthy Normal Weight and Asymptomatic Overweight Adults

Obesity and overweight are major contributors to the burden of chronic disease. Both are defined as abnormal or excessive fat accumulation and by increased production of free radicals leading to oxidative stress. The aim of the present study was to evaluate whether overweight and fat accumulation is associated with serum total antioxidant capacity (TAC) in men and women, irrespective of nutritional habits, nutrient intakes, physical activity, smoking, and other confounders, which may be responsible for modifying the association between serum TAC and overweight/obesity measures. This cross-sectional study was conducted on 60 normal weight and 60 overweight adults aged 25-49. All participants underwent standard anthromorphological measurements of body composition, blood pressure and biochemical measurements, aerobic capabilities assessment and dietary intake evaluation. TAC was measured by using the photochemioluminescence method. All data were analysed with SPSS software. Men had higher values of TAC than women and concentrations of TAC were significantly higher in overweight subjects compared to normal weight subjects. In the present study TAC tended to be increased by various metabolic risk factors, especially overweight/obesity parameters (body mass index, body fat), inflammation and increased serum levels of Cysteine, irrespective of nutritional habits, nutrient intakes, physical activity and smoking. Overweight and obesity at an early stage may stimulate TAC. Therefore, the elevation of TAC in overweight adults may be a compensatory response to oxidative stress, generated by reactive oxygen species.