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Sweet Success: Metabolic Substrate Adaptations To Acute Hypoxia In The Naked Mole Rat (Heterocephalus Glaber)
Author(s) -
Pamenter Matthew E.,
Kirby Alexia M.,
Shuhendler Adam J.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.858.8
Subject(s) - hypoxia (environmental) , carbohydrate metabolism , oxygen , mole , metabolism , adipose tissue , chemistry , medicine , endocrinology , biology , biochemistry , organic chemistry
Naked mole rats are among the most hypoxia‐tolerant mammals identified. This tolerance is partially achieved through their ability to coordinately reduce metabolic rates by > 85% in acute hypoxia while staying warm and active in their hypoxic underground burrows. Our understanding of the physiological responses that enable their hypoxia‐tolerance is improving; however, the underlying molecular and biochemical mechanisms that support this remarkable energetic suppression are poorly understood. Of particular interest is a putative metabolic fuel substrate switch in hypoxia. Naked mole rats primarily metabolize lipids in normoxia, but carbohydrate metabolism may be favored in hypoxia because carbohydrate oxidation yields more energy per molecule of oxygen than does lipid oxidation. We hypothesized that naked mole rats switch to primarily glucose‐fueled metabolism in acute hypoxia and that the energetic needs of brain and heart are prioritized over those of other tissues. Furthermore, we predicted that heat production from brown adipose tissue, which is a glucose‐intensive process, would be turned off in hypoxia as an energy‐saving strategy. To test these hypotheses, we measured metabolic fuel usage and heat production in naked mole rats exposed to acute hypoxia (7% O 2 ) using non‐invasive in vivo imaging techniques, including infrared thermography, magnetic resonance imaging (MRI), and positron emission tomography (PET). We found that glucose metabolism is markedly upregulated in heart and brain during acute hypoxia, but decreased in liver. Furthermore, heat generation from brown adipose tissue is entirely turned off in hypoxia and the naked mole rat body temperature drops to near or below ambient temperature, indicating that all endogenous heat production ceases in hypoxia. We conclude that naked mole rats maximize the energy/oxygen ratio in their metabolic fuel substrate usage and prioritize feeding the energetic needs of brain and heart over all other metabolic processes in hypoxia. Support or Funding Information This study was supported by an NSERC discovery grant to MEP, a CIHR grant to AJS, and CRC grants to MEP and AJS. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .