Maternal obesity impairs brain glucose metabolism and neural response to hyperglycemia in male rat offspring

被引:29
|
作者
Chen, Hui [1 ,2 ]
Simar, David [3 ]
Morris, Margaret J. [2 ]
机构
[1] Univ Technol Sydney, Fac Sci, Sch Med & Mol Biosci, Ctr Hlth Technol, Sydney, NSW 2007, Australia
[2] Univ New S Wales, Sch Med Sci, Dept Pharmacol, Sydney, NSW 2052, Australia
[3] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia
关键词
GLUT1; lactate production; MCTs; mTOR; NPY; POMC; SENSING NEURONS; ENERGY-BALANCE; LACTATE; FOOD; TRANSPORTERS; EXPRESSION; POMC;
D O I
10.1111/jnc.12623
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hypothalamic appetite regulators neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) are modulated by glucose. This study investigated how maternal obesity disturbs glucose regulation of NPY and POMC, and whether this deregulation is linked to abnormal hypothalamic glucose uptake-lactate conversion. As post-natal high-fat diet (HFD) can exaggerate the effects of maternal obesity, its additional impact was also investigated. Female Sprague Dawley rats were fed a HFD (20kJ/g) to model maternal obesity. At weaning, male pups were fed chow or HFD. At 9 weeks, in vivo hypothalamic NPY and POMC mRNA responses to acute hyperglycemia were measured; while hypothalami were glucose challenged in vitro to assess glucose uptake-lactate release and related gene expression. Maternal obesity dampened in vivo hypothalamic NPY response to acute hyperglycemia, and lowered in vitro hypothalamic glucose uptake and lactate release. When challenged with 20 mM glucose, hypothalamic glucose transporter 1, monocarboxylate transporters, lactate dehydrogenase-b, NPY and POMC mRNA expression were down-regulated in offspring exposed to maternal obesity. Post-natal HFD consumption reduced in vitro lactate release and monocarboxylate transporter 2 mRNA, but increased POMC mRNA levels when challenged with 20 mM glucose. Overall, maternal obesity produced stronger effects than post-natal HFD consumption to impair hypothalamic glucose metabolism. However, they both disturbed NPY response to hyperglycemia, potentially leading to hyperphagia.
引用
收藏
页码:297 / 303
页数:7
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