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

Abstract:

: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.

journal_name

J Cell Physiol

authors

Ieraci A,Barbieri SS,Macchi C,Amadio P,Sandrini L,Magni P,Popoli M,Ruscica M

doi

10.1002/jcp.29778

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

9667-9675

issue

12

eissn

0021-9541

issn

1097-4652

journal_volume

235

pub_type

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