Brain-derived neurotrophic factor, but not body weight, correlated with a reduction in depression scale scores in men with metabolic syndrome: a prospective weight-reduction study.

BACKGROUND: Obesity, a critical component of metabolic syndrome (MetS), is associated with depression. Deficiency of brain-derived neurotrophic factor (BDNF) is involved in the mechanism of depression. We hypothesized that weight reduction would improve depressive symptoms via increasing BDNF levels in obese men. METHODS: Male adults with obesity were enrolled in a weight-reduction program for twelve weeks. All subjects underwent daily caloric restriction and an exercise program which was regularly assessed in group classes. Fasting blood samples and Zung Self-Rating Depression Scale (Zung SDS) scores were collected for assessments before and after the study. RESULTS: A total of 36 subjects completed this program. The average reduction in body weight was 8.4 ± 5.1 kg (8.8 ± 5.1%, P < 0.001). Fasting serum BDNF significantly increased after the study (from 40.4 ± 7.8 to 46.9 ± 8.9 ng/ml, P < 0.001). However, the depression symptoms, as assessed by the Zung Self-Rating Depression Scale (Zung SDS), did not reduce significantly (P = 0.486). Divided into subgroups based on changes in BDNF, Zung SDS scores were significantly reduced in subjects with greater BDNF increase than in those with minor BDNF change (-3.9 ± 6.2 vs. 2.3 ± 6.7, P = 0.009). The increased percentage of BDNF was inversely correlated with the change in Zung SDS (r = -0.380, P = 0.022). Multivariate regression analysis showed that reduction in BDNF was independently associated with change in Zung SDS (95% confidence interval -0.315 to -0.052, P = 0.008). CONCLUSION: Zung SDS only significantly improved in men with increased fasting BDNF levels after a lifestyle intervention. TRIAL REGISTRATION: (NCT01065753, ClinicalTrials.gov).

Brain-derived neurotrophic factor not associated with metabolic syndrome but inversely correlated with vascular cell adhesion molecule-1 in men without diabetes.

BACKGROUND: Excessive visceral fat with unbalanced adipokines is a critical pathogenic factor of metabolic syndrome (MetS), which is associated with disorders of the central nervous system and cardiovascular disease. Because brain-derived neurotrophic factor (BDNF) plays an important role in neurons, we examined the relationship of BDNF to MetS, adipose tissue and biomarkers in men. METHODS: Thirty-four non-diabetic men with MetS and another 24 age-matched men without MetS were enrolled. In addition to fasting blood samples, the area of adipose tissue at the waist was assessed by magnetic resonance imaging (MRI). RESULTS: There was no significant difference in serum BDNF concentrations between men with or without MetS (40.9±8.0 vs. 43.2±6.1 ng/ml, P=0.235). However, the serum concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) was higher in the subjects with a lower BDNF level (737±230 vs. 628±115 ng/ml, P=0.025). An inverse correlation between VCAM-1 and BDNF was observed (r=-0.391, P=0.002). After adjusting for visceral adipose tissue, VCAM-1 was found to be independently associated with BDNF [95% confidence interval (-0.025, -0.005), P=0.004]. CONCLUSION: These data show no difference in serum BDNF levels between the men with MetS and controls. However, serum BDNF was inversely correlated with serum VCAM-1 in men without diabetes.

MRI measured epicardial adipose tissue thickness at the right AV groove differentiates inflammatory status in obese men with metabolic syndrome.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat, which secretes inflammatory cytokines and adipokines. In this study, our aim was to examine which measurements of EAT thickness by magnetic resonance imaging (MRI) could best help differentiate inflammatory status, classified by levels of high-sensitivity C-reactive protein (hs-CRP), in obese men with metabolic syndrome (MetS). We prospectively enrolled 32 men with central obesity (waist circumference ≥90 cm) and at least two other MetS criteria. MRI examinations for measurements of EAT, subcutaneous fat, and abdominal visceral fat as well as recordings of anthropometric parameters and tests for serum inflammatory cytokines and adipokines were conducted. Subjects with MetS (N = 32) were divided into three subgroups: (i) low inflammatory status (hs-CRP < 0.1 mg/dl, N = 8), [corrected] (ii) intermediate inflammatory status (hs-CRP 0.1-0.3 mg/dl, N = 15), and (iii) high inflammatory status (hs-CRP >0.3 mg/dl, N = 9). EAT thickness at the right atrioventricular (AV) groove showed a significant linear trend among the three subgroups of MetS (P for trend = 0.004). High inflammatory status MetS subgroup had a significantly thicker right AV groove EAT than did the low inflammatory status MetS subgroup (19.3 ± 3.1 vs. 14.4 ± 3.3 mm, P = 0.015). In binary logistic regression analysis, right AV groove EAT thickness was an independent predictor for differentiating inflammatory status in MetS while abdominal visceral fat area and insulin-resistance index were not. In conclusion, MRI measured EAT thickness at the right AV groove could be a useful marker for differentiating the inflammatory status in obese men with MetS.

Persistent elevation of paraoxonase-1 specific enzyme activity after weight reduction in obese non-diabetic men with metabolic syndrome.

BACKGROUND: Paraoxonase-1 (PON1) is an esterase associated with the high-density lipoprotein (HDL) in serum. To date, there have been few reports about circulating PON1 protein concentration and specific activity in subjects with metabolic syndrome (MetS). More importantly, it is unknown whether weight loss could alter PON1 protein expression or specific activity in obese non-diabetic men with MetS. METHODS: We prospectively enrolled a total of 40 obese non-diabetic men with MetS. Among them, 22 subjects finished the 3-month course of weight loss program and complied for longer follow-ups post-weight loss at the 3rd, 12th, and 18th month from the beginning of the program. Twenty-six healthy volunteers served as controls. Serum circulating PON1 concentration was measured by an enzyme linked immunosorbent kit (ELISA) and PON1 activity was measured by an automated PON1 activity assay. RESULTS: Obese non-diabetic men with MetS (n=40) had a higher PON1 protein concentration (31.0 ± 11.3 vs. 24.8 ± 9.7 µg/ml, p=0.025) but lower specific enzyme activity (7.5 ± 4.0 vs. 11.2 ± 7.2 mU/µg, p=0.023) than those of the controls. Multivariate regression analysis of baseline PON1 specific activity revealed that adiponectin was a significant positive predictor (p=0.044) while monocyte chemotactic protein-1 (MCP-1) was a negative predictor (p=0.031). After a 3-month weight loss program, obese MetS men (n=22) had a significant weight reduction (95.8 ± 9.0 to 86.3 ± 10.4 kg, with a 9.9 ± 5.4% decrease, p<0.001). PON1 protein decreased significantly after weight loss and kept declining through the 3rd month till the 18th month follow-up. PON1 specific enzyme activity (baseline 7.5 ± 2.6 mU/µg) increased significantly after weight loss and kept increasing through the 12th month till the 18th month follow-ups (11.8 ± 6.4 mU/µg, p=0.001 vs. baseline). CONCLUSIONS: Weight loss by a 3-month diet and exercise program time-sequentially increased PON1 specific enzyme activity in obese non-diabetic men with MetS.

Metabolic syndrome associated with habitual indulgence and dietary behavior in middle-aged health-care professionals.

UNLABELLED: Aims/Introduction: Few studies, especially in Asia, have examined the relevance between metabolic syndrome (MetS), habitual indulgence and dietary behaviors in health-care professionals. The present study evaluates metabolic syndrome rate and its association with habitual indulgence (coffee, tea, alcohol and cigarette smoking) and diet behavior in health-care professionals. MATERIALS AND METHODS: Information was collected from 514 health-care professionals (147 men, 367 women) who underwent routine physical examinations at a medical center in central Taiwan. RESULTS: Mean age was 48 ± 5 years for men and 45 ± 4 years for women. Mean body mass index was 25.2 ± 4.0 kg/m(2) for men and 22.5 ± 3.4 kg/m(2) for women. The age-adjusted MetS rate among subjects was 24.8-11.7% in men and 7.8-5.4% in women, using two different definitions, respectively. The MetS rate among those who occasionally or frequently consumed tea was higher than among those who never consumed tea (P < 0.05). Although the proportion of subjects who had MetS differed among those with differing alcohol drinking habits (never, quit and current; P < 0.05), a posteriori comparisons showed no significant differences between the two groups. Compared with those who had never smoked, the rate was higher in former smokers and current smokers (P < 0.001). No significant association with coffee consumption was found. People with MetS often consumed sweetened beverages (P < 0.05), rarely read nutrition labels and seldom consumed dairy products. CONCLUSIONS: Health-care professionals who regularly consume tea, smoke, frequently have sweetened drinks, rarely read nutrition labels or rarely consume dairy products are at higher risk of suffering from MetS. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00055.x, 2010).

Effect of weight loss on proinflammatory state of mononuclear cells in obese women.

In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB.

Prospective evaluation of folic acid supplementation on plasma homocysteine concentrations during weight reduction: a randomized, double-blinded, placebo-controlled study in obese women.

Elevated total homocysteine concentrations and obesity are both associated with an increased risk of cardiovascular disease. However, previous studies of weight reduction on serum homocysteine concentrations have obtained inconsistent reports. We investigated the effect of folic acid supplementation on serum homocysteine concentrations via a randomized, double-blinded, placebo-controlled study. Seventy-four obese women [age (mean +/- SEM) 41 +/- 1 years; body mass index, 29.6 +/- 0.5 kgs/m2] completed a 12 weeks weight reduction program with dietary advice and light exercise. They were also randomized to take either folic acid supplementation (5 mg daily, n = 36) or placebo (n = 38) groups. This program led to a weight reduction of 7.7% and 8.9% of initial weight for folic acid supplementation and placebo groups, respectively. Serum folate concentrations increased for 3 folds (p < 0.001) in the folic acid group. In the folic acid group, there was a trend of lower fasting serum homocysteine concentrations (7.6 +/- 0.2 vs. 7.3 +/- 0.3 micromol/L), but it did not reach statistical significance (p = 0.170). However, we found that serum homocysteine concentrations decreased significantly in those with higher baseline homocysteine concentrations (8.7 +/- 1.3 vs. 7.8 +/- 1.5 micromol/L, p = 0.004), while it did not change in those with lower baseline homocysteine concentrations (6.6 +/- 0.6 vs. 6.8 +/- 1.2 micromol/L, p = 0.334). Reduction of serum homocysteine concentrations did not correlate with elevation of serum folate concentrations (p = 0.646) in obese women with higher baseline homocysteine concentrations. In conclusion, serum homocysteine concentrations can be maintained in obese women during mild to moderate weight loss. Folic acid supplementation decreased serum homocysteine concentrations in those women who had higher serum homocysteine concentrations before participating in the weight reduction program.