TY - JOUR
T1 - BDNF Val66Met polymorphism alters food intake and hypothalamic BDNF expression in mice
AU - Ieraci, Alessandro
AU - Barbieri, Silvia S.
AU - Macchi, Chiara
AU - Amadio, Patrizia
AU - Sandrini, Leonardo
AU - Magni, Paolo
AU - Popoli, Maurizio
AU - Ruscica, Massimiliano
N1 - Funding Information:
We thank Alessandra Mallei for some preliminary experiments. Original BDNF Val66Met mice were provided by Francis S. Lee. This study was supported by grants MIUR (PRIN 2010N8PBAA) to MP, and Fondazione CARIPLO (2015-0552 and 2018-0511) to MR and is part of the collaborative consortium ?Italian Network on BDNF? (InBDNF).
Publisher Copyright:
© 2020 Wiley Periodicals LLC
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - BDNF Val66Met polymorphism
KW - food intake
KW - glucose metabolism
KW - leptin
KW - overweight
UR - http://www.scopus.com/inward/record.url?scp=85085022819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085022819&partnerID=8YFLogxK
U2 - 10.1002/jcp.29778
DO - 10.1002/jcp.29778
M3 - Article
C2 - 32430940
AN - SCOPUS:85085022819
VL - 235
SP - 9667
EP - 9675
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 1097-4652
IS - 12
ER -