Abstract
Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in humans and rodents. Maternal diet is a major determinant of offspring health, and there is strong evidence that maternal HFD alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. In this study, we exposed pregnant and lactating C57BL/6JB female mice to either HFD, HFD with supplemented BCAA (HFD+BCAA), or standard diet (SC), and we studied offspring metabolic phenotypes. Both maternal HFD and HFD supplemented with BCAA had similar effect rendering the offspring metabolic imbalance and impairing their ability to cope with HFD when challenged during aging. The metabolic effects of HFD challenge were more profound in females, worsening female offspring ability to cope with an HFD challenge by activating hypothalamic inflammation in aging. Moreover, the sex differences in hypothalamic estrogen receptor α (ER-α) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-α levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E526-E534 |
| Journal | American journal of physiology. Endocrinology and metabolism |
| Volume | 317 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2019 |
Fingerprint
Keywords
- BCAA
- hypothalamic inflammation
- maternal nutrition
- metabolic reprogramming
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Physiology (medical)
Cite this
Sexual dimorphism in hypothalamic inflammation in the offspring of dams exposed to a diet rich in high fat and branched-chain amino acids. / Sadagurski, Marianna; Debarba, Lucas Kniess; Werneck-de-Castro, Joao Pedro; Ali Awada, Abear; Baker, Tess A.; Bernal Mizrachi, Ernesto.
In: American journal of physiology. Endocrinology and metabolism, Vol. 317, No. 3, 01.09.2019, p. E526-E534.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sexual dimorphism in hypothalamic inflammation in the offspring of dams exposed to a diet rich in high fat and branched-chain amino acids
AU - Sadagurski, Marianna
AU - Debarba, Lucas Kniess
AU - Werneck-de-Castro, Joao Pedro
AU - Ali Awada, Abear
AU - Baker, Tess A.
AU - Bernal Mizrachi, Ernesto
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in humans and rodents. Maternal diet is a major determinant of offspring health, and there is strong evidence that maternal HFD alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. In this study, we exposed pregnant and lactating C57BL/6JB female mice to either HFD, HFD with supplemented BCAA (HFD+BCAA), or standard diet (SC), and we studied offspring metabolic phenotypes. Both maternal HFD and HFD supplemented with BCAA had similar effect rendering the offspring metabolic imbalance and impairing their ability to cope with HFD when challenged during aging. The metabolic effects of HFD challenge were more profound in females, worsening female offspring ability to cope with an HFD challenge by activating hypothalamic inflammation in aging. Moreover, the sex differences in hypothalamic estrogen receptor α (ER-α) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-α levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.
AB - Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in humans and rodents. Maternal diet is a major determinant of offspring health, and there is strong evidence that maternal HFD alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. In this study, we exposed pregnant and lactating C57BL/6JB female mice to either HFD, HFD with supplemented BCAA (HFD+BCAA), or standard diet (SC), and we studied offspring metabolic phenotypes. Both maternal HFD and HFD supplemented with BCAA had similar effect rendering the offspring metabolic imbalance and impairing their ability to cope with HFD when challenged during aging. The metabolic effects of HFD challenge were more profound in females, worsening female offspring ability to cope with an HFD challenge by activating hypothalamic inflammation in aging. Moreover, the sex differences in hypothalamic estrogen receptor α (ER-α) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-α levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.
KW - BCAA
KW - hypothalamic inflammation
KW - maternal nutrition
KW - metabolic reprogramming
UR - http://www.scopus.com/inward/record.url?scp=85071708773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071708773&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00183.2019
DO - 10.1152/ajpendo.00183.2019
M3 - Article
VL - 317
SP - E526-E534
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 3
ER -