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.

BDNF Val66Met polymorphism alters food intake and hypothalamic BDNF expression in mice / A. Ieraci, S.S. Barbieri, C. Macchi, P. Amadio, L. Sandrini, P. Magni, M. Popoli, M. Ruscica. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - (2020). [Epub ahead of print] [10.1002/jcp.29778]

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

A. Ieraci
Primo
Writing – Original Draft Preparation
;
S.S. Barbieri
Secondo
Conceptualization
;
C. Macchi
Methodology
;
P. Amadio
Methodology
;
L. Sandrini
Methodology
;
P. Magni
Writing – Original Draft Preparation
;
M. Popoli
Penultimo
Writing – Review & Editing
;
M. Ruscica
Ultimo
Writing – Original Draft Preparation
2020

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.
BDNF
Settore BIO/14 - Farmacologia
Settore MED/04 - Patologia Generale
Fisiologia e fisiopatologia di BDNF: verso lo sviluppo di nuove strategie terapeutiche per alcune delle principali malattie neuro-psichiatriche
mag-2020
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/735925
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