Circulating brain-derived neurotrophic factor concentration is downregulated by intralipid/heparin infusion or high-fat meal in young healthy male subjects.
OBJECTIVE
Insulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) regulates neuronal differentiation and synaptic plasticity, and its decreased levels are supposed to play a role in the pathogenesis of Alzheimer's disease and other disorders. The aim of the current study was to estimate the effects of hyperinsulinemia and serum free fatty acids (FFA) elevation on circulating BDNF concentration in humans.


METHODS
We studied 18 healthy male subjects (mean age 25.6 ± 3.0 years; mean BMI 26.6 ± 4.8 kg/m(2)). Serum and plasma BDNF concentration was measured in the baseline state and in the 120 and 360 min of euglycemic hyperinsulinemic clamp with or without intralipid/heparin infusion. Furthermore, plasma BDNF was measured in 20 male subjects (mean age 22.7 ± 2.3 years; mean BMI 24.9 ± 1.5 kg/m(2)) 360 min after a high-fat meal.


RESULTS
Insulin sensitivity was reduced by ~40% after 6 h of intralipid/heparin infusion (P < 0.001). During both clamps, serum and plasma BDNF followed the same pattern. Hyperinsulinemia had no effect on circulating BDNF. Raising FFA had no effect on circulating BDNF in 120 min; however, it resulted in a significant decrease by 43% in serum and by 35% in plasma BDNF after 360 min (P = 0.005 and 0.006, respectively). High-fat meal also resulted in a decrease by 27.8% in plasma BDNF (P = 0.04).


CONCLUSIONS
Our data show that raising FFA decreases circulating BDNF. This might indicate a potential link between FFA-induced insulin resistance and neurodegenerative disorders.
Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
Monika
M
Karczewska-Kupczewska
Irina
I
Kowalska
Agnieszka
A
Nikołajuk
Agnieszka
A
Adamska
Magdalena
M
Zielińska
Natalia
N
Kamińska
Elżbieta
E
Otziomek
Maria
M
Górska
Marek
M
Strączkowski
D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004655:Emulsions / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects / Q000097:blood; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D013024:Soybean Oil / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D006493:Heparin