Brain-derived neurotrophic factor ameliorates lipid metabolism in diabetic mice

It has been reported previously that brain-derived neurotrophic factor (BDNF) regulates blood glucose metabolism in rodent obese diabetic models such as C57BL/KsJ-leprdb/leprdb (db/db) mice. BDNF further regulates energy expenditure, possibly through the central and autonomous nervous systems. In this study, we evaluated the effect of BDNF on both lipid and glucose metabolisms to clarify its action mechanism.

To control the energy intake, we used a pellet pair-feeding apparatus to synchronize food intake precisely between BDNF-treated and vehicle-treated db/db mice. BDNF (50 mg/kg/week) was subcutaneously injected to male db/db mice twice weekly for 3 weeks, and blood glucose, serum biochemical lipid parameters and tissue weights were measured. Liver triglyceride contents were measured and liver sections were histologically analysed.

Twice weekly BDNF treatment for 3 weeks significantly lowered blood glucose compared with pellet pair-fed, vehicle-treated db/db mice (294 +/- 109 vs. 529 +/- 91 mg/dL). Serum non-esterified free fatty acid (726 +/- 72 vs. 999 +/- 220 microEq/l), total cholesterol (125 +/- 8 vs. 151 +/- 23 mg/dL) and phospholipid levels (215 +/- 13 vs. 257 +/- 36 mg/dL) of the BDNF-treated db/db mice decreased significantly. Liver weights (1.51 +/- 0.11 vs. 2.05 +/- 0.11 g), liver triglyceride contents (17.5 +/- 1.4 vs. 26.1 +/- 2.1 mg/g) and fatty liver in histological appearance were reduced with BDNF treatment. There were no significant differences in body weights and white adipose tissue weights between the two groups.

Taken together with the accelerating effect of BDNF on energy metabolism, these findings indicate that BDNF improves glucose and lipid metabolism in obese diabetic animals without enlarging liver or adipose tissues.