High-fat diet and FGF21 cooperatively promote aerobic thermogenesis in mtDNA mutator mice

Christopher E. Wall, Jamie Whyte, Jae M. Suh, Weiwei Fan, Brett Collins, Christopher Liddle, Ruth T. Yu, Annette R. Atkins, Jane C. Naviaux, Kefeng Li, Andrew Taylor Bright, William A. Alaynick, Michael Downes, Robert K. Naviaux, Ronald M. Evans

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44 引文 斯高帕斯(Scopus)


Mitochondria are highly adaptable organelles that can facilitate communication between tissues to meet the energetic demands of the organism. However, the mechanisms by which mitochondria can nonautonomously relay stress signals remain poorly understood. Here we report that mitochondrial mutations in the young, preprogeroid polymerase gamma mutator (POLG) mouse produce a metabolic state of starvation. As a result, these mice exhibit signs of metabolic imbalance including thermogenic defects in brown adipose tissue (BAT). An unexpected benefit of this adaptive response is the complete resistance to diet-induced obesity when POLG mice are placed on a high-fat diet (HFD). Paradoxically, HFD further increases oxygen consumption in part by inducing thermogenesis and mitochondrial biogenesis in BAT along with enhanced expression of fibroblast growth factor 21 (FGF21). Collectively, these findings identify a mechanistic link between FGF21, a longknown marker of mitochondrial disease, and systemic metabolic adaptation in response to mitochondrial stress.

頁(從 - 到)8714-8719
期刊Proceedings of the National Academy of Sciences of the United States of America
出版狀態Published - 14 7月 2015


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