BDNF Val66Met polymorphism alters food intake and hypothalamic BDNF expression in mice

Obesity, a rising public health burden, is a multifactorial disease with an increased
risk for patients to develop several pathological conditions including type 2 diabetes
mellitus, hypertension, and cardiovascular disease. Increasing evidence suggests a
relationship between the human brain‐derived neurotrophic factor (BDNF)
Val66Met single‐nucleotide polymorphism (SNP) and obesity, although the underlying
mechanisms of this connection are still not completely understood. In the
present study, we found that homozygous knock‐in BDNFMet/Met mice were overweight
and hyperphagic compared to wildtype BDNFVal/Val mice. Increased food
intake was associated with reduction of total BDNF and BDNF1, BDNF4 and BDNF6
transcripts in the hypothalamus of BDNFMet/Met mice. In contrast, in the white
adipose tissue total BDNF and Glut4 expression levels were augmented, while
sirtuin 1 and leptin receptor (Ob‐R) expression levels were reduced in BDNFMet/Met
mice. Moreover, plasmatic leptin levels were decreased in BDNFMet/Met mice.
However, BDNFVal/Val and BDNFMet/Met mice showed a similar response to the insulin
tolerance test and glucose tolerance test. Altogether, these results suggest that
BDNF Val66Met SNP strongly contributes to adipose tissue pathophysiology,
resulting in reduced circulating leptin levels and hypothalamic expression of BDNF,
which, in turn, promote increased food intake and overweight in BDNFMet/Met mice.