Circulating brain-derived neurotrophic factor and indices of metabolic and cardiovascular health: data from the Baltimore Longitudinal Study of Aging

Abstract

Background: Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.

Methodology/principal findings: To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age approximately 70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.

Conclusion/significance: Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined.

Figure 1. Plasma BDNF, gender and age.

A. Plasma BDNF was significantly higher in females than in males (p<0.05). B and C. Multiple linear regression revealed that plasma BDNF was inversely correlated with age in males (p = 0.0501, R² = 0.01577) and in females (p = 0.0220, R² = 0.02244).

Figure 2. Linear regression analysis correlating plasma BDNF and markers of cardiovascular risk in females.

A, B and C. Plasma BDNF was positively correlated with diastolic blood pressure (p<0.05, R² = 0.0228), LDL-cholesterol (p = 0.139, R² = 0.02634), and total cholesterol (p = 0.0040, R² = 0.03487). D. Folate levels were inversely correlated with plasma BDNF (p = 0.0396, R² = 0.01885).

Figure 3. Linear regression analysis of plasma BDNF, fat mass and BMI in females.

A and B. Plasma BDNF was positively correlated with fat mass (p = 0.0490, R² = 0.01825) and BMI (p = 0.0396, R² = 0.01843).

Figure 4. Linear regression analysis correlating plasma BDNF and markers of the metabolic syndrome in males.

A, B and C. Plasma BDNF was positively correlated with diastolic blood pressure (p = 0.0300, R² = 0.01971), triglycerides (p = 0.0289, R² = 0.02016), and bioavailable testosterone (p = 0.0443, R² = 0.01755). D. Plasma BDNF was inversely correlated with SHBG (p = 0.0150, R² = 0.03489).

Figure 5. Linear regression analysis correlating plasma BDNF with thyroid function, adiponectin levels and glucose sensitivity in males.

A and C. Plasma BDNF was positively correlated with FT3 (p = 0.0053, R² = 0.03348) and glucose-120 (p = 0.0460, R² = 0.02170). B. Plasma BDNF was inversely correlated with plasma adiponectin (p = 0.0137, R² = 0.04650).