1. SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction
- Author
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Stephen E Flaherty III, Olivier Bezy, Brianna LaCarubba Paulhus, LouJin Song, Mary Piper, Jincheng Pang, Yoson Park, Shoh Asano, Yu-Chin Lien, John D Griffin, Andrew Robertson, Alan Opsahl, Dinesh Hirenallur Shanthappa, Youngwook Ahn, Evanthia Pashos, Rebecca A Simmons, Morris J Birnbaum, and Zhidan Wu
- Subjects
SPAG7 ,embryonic development ,obesity ,insulin resistance ,intrauterine growth restriction ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the Spag7 gene linked to metabolic dysfunction in mice. Here, we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a ‘thrifty phenotype’ is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.
- Published
- 2024
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