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Enhanced lipogenesis through Pparγ helps cavefish adapt to food scarcity

Shaolei Xiong, Wei Wang, Alexander Kenzior, Luke Olsen, Jaya Krishnan, Jenna Persons, Kyle Medley, Robert Peuß, Yongfu Wang, Shiyuan Chen, Ning Zhang, Nancy Thomas, John M. Miles, View ORCID ProfileAlejandro Sánchez Alvarado, View ORCID ProfileNicolas Rohner
doi: https://doi.org/10.1101/2021.04.27.441667
Shaolei Xiong
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Wei Wang
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
2Howard Hughes Medical Institute, Kansas City, MO 64110, USA
3National Institute of Biological Sciences, Beijing 102206, China
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Alexander Kenzior
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Luke Olsen
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
4Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
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Jaya Krishnan
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Jenna Persons
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Kyle Medley
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Robert Peuß
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
5Institute for Evolution and Biodiversity, University of Münster, Münster 48149, Germany
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Yongfu Wang
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Shiyuan Chen
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Ning Zhang
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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Nancy Thomas
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
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John M. Miles
6Department of Medicine, Division of Metabolism, Endocrinology & Genetics, University of Kansas Medical Center, Kansas City, KS 66160, USA
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Alejandro Sánchez Alvarado
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
2Howard Hughes Medical Institute, Kansas City, MO 64110, USA
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Nicolas Rohner
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA
4Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
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  • For correspondence: nro@stowers.org
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Abstract

Nutrient availability varies seasonally and spatially in the wild. The resulting nutrient limitation or restricted access to nutrients pose a major challenge for every organism. While many animals, such as hibernating animals, evolved strategies to overcome periods of nutrient scarcity, the cellular mechanisms of these strategies are poorly understood. Cave environments represent an extreme example of nutrient deprived environments since the lack of sunlight and therefore primary energy production drastically diminishes the nutrient availability. Here, we used Astyanax mexicanus, which includes river-dwelling surface fish and cave adapted cavefish populations to study the genetic adaptation to nutrient limitations. We show that cavefish populations store large amounts of fat in different body regions when fed ad libitum in the lab. We found higher expression of lipogenesis genes in cavefish livers when fed the same amount of food as surface fish, suggesting an improved ability of cavefish to use lipogenesis to convert available energy into triglycerides for storage into adipose tissue. Moreover, the lipid metabolism regulator, Peroxisome proliferator-activated receptor γ (Pparγ), is upregulated at both transcript and protein levels in cavefish livers. Chromatin Immunoprecipitation sequencing (ChIP seq) showed that Pparγ binds cavefish promoter regions of genes to a higher extent than surface fish. Finally, we identified two possible regulatory mechanisms of Pparγ in cavefish: higher amounts of ligands of the nuclear receptor, and nonsense mutations in per2, a known repressor of Pparγ. Taken together, our study reveals that upregulated Pparγ promotes higher levels of lipogenesis in the liver and contributes to higher body fat accumulation in cavefish populations, an important adaptation to nutrient limited environments.

Competing Interest Statement

The authors have declared no competing interest.

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Posted April 28, 2021.
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Enhanced lipogenesis through Pparγ helps cavefish adapt to food scarcity
Shaolei Xiong, Wei Wang, Alexander Kenzior, Luke Olsen, Jaya Krishnan, Jenna Persons, Kyle Medley, Robert Peuß, Yongfu Wang, Shiyuan Chen, Ning Zhang, Nancy Thomas, John M. Miles, Alejandro Sánchez Alvarado, Nicolas Rohner
bioRxiv 2021.04.27.441667; doi: https://doi.org/10.1101/2021.04.27.441667
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Enhanced lipogenesis through Pparγ helps cavefish adapt to food scarcity
Shaolei Xiong, Wei Wang, Alexander Kenzior, Luke Olsen, Jaya Krishnan, Jenna Persons, Kyle Medley, Robert Peuß, Yongfu Wang, Shiyuan Chen, Ning Zhang, Nancy Thomas, John M. Miles, Alejandro Sánchez Alvarado, Nicolas Rohner
bioRxiv 2021.04.27.441667; doi: https://doi.org/10.1101/2021.04.27.441667

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