PMID- 36505238 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221221 IS - 2296-861X (Print) IS - 2296-861X (Electronic) IS - 2296-861X (Linking) VI - 9 DP - 2022 TI - A low carbohydrate diet high in fish oil and soy protein delays inflammation, hematopoietic stem cell depletion, and mortality in miR-146a knock-out mice. PG - 1017347 LID - 10.3389/fnut.2022.1017347 [doi] LID - 1017347 AB - Since our previous studies found a low carbohydrate (CHO) diet containing soy protein and fish oil (15%Amylose/Soy/FO) significantly reduced lung and breast cancer in mice we asked herein if this low CHO diet could also delay the onset of myeloid malignancies. To test this we employed a miR-146a knock-out (KO) mouse model and found the 15%Amylose/Soy/FO diet increased their median lifespan by 8.5 month, compared to these mice on a Western diet. This was associated with increased lymphocytes and reduced monocytes, granulocytes, blood glucose and insulin levels. Inflammatory cytokine/chemokine studies carried out with 6-month-old mice, before any signs of illness, revealed the 15%Amylose/Soy/FO diet significantly reduced pro-inflammatory cytokines. This low CHO diet also led to an increase in plasma beta-hydroxybutyrate and in liver fatty acid synthase levels. This, together with higher liver carnitine palmitoyltransferase I levels suggested that the 15%Amylose/Soy/FO diet was causing a systemic metabolic shift from glucose to fatty acids as an energy source. Lastly, we found the 15%Amylose/Soy/FO diet resulted in significantly higher numbers of primitive hematopoietic stem cells (HSCs) in the bone marrow of 6-month-old mice than those fed a Western diet. Taken together, these results suggest a 15%Amylose/Soy/FO diet reduces chronic inflammation and increases fatty acid oxidation and that this, in turn, may prevent HSC proliferation and exhaustion, thereby delaying myeloid malignancy-induced death of miR-146a KO mice. We suggest a low CHO diet containing soy protein and fish oil could be beneficial in reducing the risk of myeloid malignancies in patients with low miR-146a levels. CI - Copyright (c) 2022 Elisia, Kowalski, Yeung, Wong, Grants, Karsan and Krystal. FAU - Elisia, Ingrid AU - Elisia I AD - The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada. FAU - Kowalski, Sara AU - Kowalski S AD - The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada. FAU - Yeung, Michelle AU - Yeung M AD - The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada. FAU - Wong, Jennifer AU - Wong J AD - The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada. FAU - Grants, Jennifer M AU - Grants JM AD - Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Centre, Vancouver, BC, Canada. FAU - Karsan, Aly AU - Karsan A AD - Canada's Michael Smith Genome Sciences Centre, BC Cancer Research Centre, Vancouver, BC, Canada. FAU - Krystal, Gerald AU - Krystal G AD - The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada. LA - eng PT - Journal Article DEP - 20221124 PL - Switzerland TA - Front Nutr JT - Frontiers in nutrition JID - 101642264 PMC - PMC9729559 OTO - NOTNLM OT - HSC exhaustion OT - inflammation OT - low carbohydrate diet OT - miR-146a OT - stem cell COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/13 06:00 MHDA- 2022/12/13 06:01 PMCR- 2022/01/01 CRDT- 2022/12/12 10:56 PHST- 2022/08/11 00:00 [received] PHST- 2022/11/08 00:00 [accepted] PHST- 2022/12/12 10:56 [entrez] PHST- 2022/12/13 06:00 [pubmed] PHST- 2022/12/13 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fnut.2022.1017347 [doi] PST - epublish SO - Front Nutr. 2022 Nov 24;9:1017347. doi: 10.3389/fnut.2022.1017347. eCollection 2022.