TY - JOUR
T1 - Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia
AU - Auvinen, Juha
AU - Tapio, Joona
AU - Karhunen, Ville
AU - Kettunen, Johannes
AU - Serpi, Raisa
AU - Dimova, Elitsa Y.
AU - Gill, Dipender
AU - Soininen, Pasi
AU - Tammelin, Tuija
AU - Mykkänen, Juha
AU - Puukka, Katri
AU - Kähönen, Mika
AU - Raitoharju, Emma
AU - Lehtimäki, Terho
AU - Ala-Korpela, Mika
AU - Raitakari, Olli T.
AU - Keinänen-Kiukaanniemi, Sirkka
AU - Järvelin, Marjo Riitta
AU - Koivunen, Peppi
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.abi4822
DO - 10.1126/sciadv.abi4822
M3 - Article
AN - SCOPUS:85110774495
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 29
M1 - eabi4822
ER -