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 - Awada, Abear Ali
AU - Baker, Tess A.
AU - Bernal-Mizrachi, Ernesto
N1 - Funding Information:
This project was supported by National Institutes of Health Grant R01-DK-084236, R01-DK-073716, and Merit Review Award IBX002728A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program for E. Bernal-Mizrachi. Additional funding includes American Diabetes Association Grant 1-lB-IDF-063 and a Feasibility Grant from the Michigan Diabetes Research Center (P30DK020572) for M. Sadagurski.
PY - 2019
Y1 - 2019
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
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U2 - 10.1152/ajpendo.00183.2019
DO - 10.1152/ajpendo.00183.2019
M3 - Article
C2 - 31361548
AN - SCOPUS:85071708773
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 -