期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 317, 期 3, 页码 E526-E534出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00183.2019
关键词
BCAA; hypothalamic inflammation; maternal nutrition; metabolic reprogramming
资金
- National Institutes of Health [R01-DK-084236, R01-DK-073716]
- Merit Review Award from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program [IBX002728A]
- American Diabetes Association [1-lB-IDF-063]
- Feasibility Grant from the Michigan Diabetes Research Center [P30DK020572]
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 alpha (ER-alpha) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-alpha levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.
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