A1 Refereed original research article in a scientific journal
Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia
Authors: Auvinen Juha, Tapio Joona, Karhunen Ville, Kettunen Johannes, Serpi Raisa, Dimova Elitsa Y, Gill Dipender, Soininen Pasi, Tammelin Tuija, Mykkänen Juha, Puukka Katri, Kähonen Mika, Raitoharju Emma, Lehtimäki Terho, Ala-Korpela Mika, Raitakari Olli T, Keinänen-Kiukaanniemi Sirkka, Järvelin Marjo-Riitta, Koivunen Peppi
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Publication year: 2021
Journal: Science Advances
Journal name in source: SCIENCE ADVANCES
Journal acronym: SCI ADV
Article number: ARTN eabi4822
Volume: 7
Issue: 29
Number of pages: 12
ISSN: 2375-2548
DOI: https://doi.org/10.1126/sciadv.abi4822
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/66661574
Activation of the hypoxia-inducible factor (HIF) pathway reprograms energy metabolism. Hemoglobin (Hb) is the main carrier of oxygen. Using its normal variation as a surrogate measure for hypoxia, we explored whether lower Hb levels could lead to healthier metabolic profiles in mice and humans (n = 7175) and used Mendelian randomization (MR) to evaluate potential causality (n = 173,480). The results showed evidence for lower Hb levels being associated with lower body mass index, better glucose tolerance and other metabolic profiles, lower inflammatory load, and blood pressure. Expression of the key HIF target genes SLC2A4 and Slc2a1 in skeletal muscle and adipose tissue, respectively, associated with systolic blood pressure in MR analyses and body weight, liver weight, and adiposity in mice. Last, manipulation of murine Hb levels mediated changes to key metabolic parameters. In conclusion, low-end normal Hb levels may be favorable for metabolic health involving mild chronic activation of the HIF response.
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