Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia

Copyright © 2021 The Authors. 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.Academy of Finland grants 266719 and 308009; S. Jusélius Foundation; Emil Aaltonen Foundation; Jane and Aatos Erkko Foundation; Academy of Finland Profi 5 funding for mathematics and AI: data insight for high-dimensional dynamics and the Academy of Finland Project 312123; British Heart Foundation Centre of Research Excellence (RE/18/4/34215); National Institute for Health Research Clinical Lectureship (CL-2020-16-001) at St. George’s, University of London. NFBC1966; University of Oulu grant nos. 65354 and 24000692; Oulu University Hospital grant nos. 2/97, 8/97, and 24301140; Ministry of Health and Social Affairs grant nos. 23/251/97, 160/97, and 190/97; National Institute for Health and Welfare, Helsinki grant no. 54121; Regional Institute of Occupational Health, Oulu, Finland grant nos. 50621 and 54231; ERDF European Regional Development Fund grant no. 539/2010 A31592; the European Union’s Horizon 2020 research and innovation programme grant agreement nos. 633595 (DynaHEALTH), 733206 (LifeCycle), 643774 (iHEALTH-T2D), 824989 (EUCAN Connect), and 721567 (EU H2020-MSCA-ITN-2016 CAPICE Marie Sklodowska-Curie), and grant nos. MR/M013138/1, MRC/BBSRC, and MR/S03658X/1 (the Medical Research Council, UK, JPI HDHL); and Academy of Finland, University Hospital Oulu, and NHLBI grant 5R01HL087679-02 through the STAMPEED program; The Young Finns Study has been financially supported by the Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere, and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; and Diabetes Research Foundation of Finnish Diabetes Association; European Union’s Horizon 2020 research and innovation programme under grant agreement no. 848146; grant agreement 755320 for TAXINOMISIS; European Research Council (grant 742927 for MULTIEPIGEN project); and Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry

High-fiber rye bread improves bowel function in postmenopausal women but does not cause other putatively positive changes in the metabolic activity of intestinal microbiota

We have reported previously that rye bread (RB) as a part of the conventional diet affects bowel function and the metabolic activity of the microbiota differently in men and women. Because a higher intake of fiber by men could explain the difference in response, in the present randomized crossover trial, we studied the effects of a RB with increased fiber content vs white wheat bread (WB) in 39 postmenopausal women aged 59 ± 6 years (mean ± SD). The women consumed RB and WB for 8 weeks in random order. The composition of fecal microbiota; activities of bacterial β-glucosidase, β-glucuronidase, and urease; and concentration of short-chain fatty acids in feces, concentration of plasma enterolactone, fecal frequency, and consistency were determined. Mean intakes of dietary fiber were 47 ± 9 and 15 ± 4 g during the RB and WB periods, respectively. Rye bread significantly increased fecal frequency and produced softer stools, and increased the concentration of plasma enterolactone and the activities of β-glucosidase and urease as compared with WB (P < .05). There were no differences in the composition of the fecal microbiota, the activity of β-glucuronidase, and the concentration of short-chain fatty acids in feces between the test bread periods. This study shows that RB in comparison to WB improves bowel function and increases the concentration of plasma enterolactone in postmenopausal women, thus improving bowel health. However, lack of other putatively positive changes observed previously in men consuming RB indicates possible sex differences in the response of colonic microbiota to dietary fiber. © 2007 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Potential Health Benefits of Anthocyanins in Oxidative Stress Related Disorders

Anthocyanins are naturally occurring water-soluble plant pigments belonging to the flavonoids chemical class. The red, blue and purple colours of leaves, flowers and fruits of plants confirm that they are rich sources of anthocyanins. Many in vivo and in vitro studies reveal that anthocyanins have different health beneficial effects such as antioxidant, antidiabetic, anti-inflammatory, anti-obesity, antihypertensive and anticancer properties. Major benefits of anthocyanin administration are owing to their potent anti-inflammatory and antioxidant activities. Recent investigations have revealed that anti-inflammatory activities of anthocyanins follow the inhibitory pathways of NFкB-mediated decline of inflammatory cytokines production. Inhibition of the anti-inflammatory pathways also influences the modulation of arteriolar disorders and cardiovascular complications due to anthocyanin administration. Moreover, anthocyanins improve diabetes, obesity and cancer pathology by inhibiting NF-кB-mediated inflammatory pathways. However, considerable variations in activities do exist among structurally diverse anthocyanins. This review appraises the recent literature regarding the health benefits of anthocyanins and their molecular mechanisms in various oxidative stress related pathophysiological conditions