Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia
Karhunen Ville; Kettunen Johannes; Soininen Pasi; Tammelin Tuija; Auvinen Juha; Raitakari Olli T; Tapio Joona; Puukka Katri; Raitoharju Emma; Serpi Raisa; Ala-Korpela Mika; Kähonen Mika; Järvelin Marjo-Riitta; Lehtimäki Terho; Keinänen-Kiukaanniemi Sirkka; Koivunen Peppi; Mykkänen Juha; Dimova Elitsa Y; Gill Dipender
Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia
Karhunen Ville
Kettunen Johannes
Soininen Pasi
Tammelin Tuija
Auvinen Juha
Raitakari Olli T
Tapio Joona
Puukka Katri
Raitoharju Emma
Serpi Raisa
Ala-Korpela Mika
Kähonen Mika
Järvelin Marjo-Riitta
Lehtimäki Terho
Keinänen-Kiukaanniemi Sirkka
Koivunen Peppi
Mykkänen Juha
Dimova Elitsa Y
Gill Dipender
AMER ASSOC ADVANCEMENT SCIENCE
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021093048352
https://urn.fi/URN:NBN:fi-fe2021093048352
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]