Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Mihaylova, Maria M.; Cheng, Chia Wei; Cao, Amanda Q.; Tripathi, Saurabh; Mana, Miyeko; Bauer-Rowe, Khristian E.; Abu-Remaileh, Monther; Clavain, Laura; Erdemir, Ayşegül Demirhan; Lewis, Caroline A.; Freinkman, Elizaveta; Dickey, Audrey S.; Spada, Albert R. La; Huang, Yanmei; Bell, George W.; Deshpande, Vikram; Carmeliet, Peter; Katajisto, Pekka; Sabatini, David M.; Yılmaz, Ömer H.

doi:10.1016/j.stem.2018.04.001

Cited by 293 publications

(361 citation statements)

References 59 publications

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“…Both led to an increase in ISC number and function (Beyaz et al, 2016;Mihaylova et al, 2018). However, while fasting improved ISC function during aging and regeneration (Mihaylova et al, 2018), HFD enhanced the capacity of ISCs to promote tumors upon loss of Apc (Beyaz et al, 2016). A recent study confirmed that FAO is required for ISC maintenance under normal conditions in mice .…”

Section: Fatty Acid Oxidationmentioning

confidence: 99%

“…In mammals, both a high fat diet (HFD) and fasting regimens have been shown to promote FAO through PPARδ, and CPT1A in the case of fasting. Both led to an increase in ISC number and function (Beyaz et al, 2016;Mihaylova et al, 2018). However, while fasting improved ISC function during aging and regeneration (Mihaylova et al, 2018), HFD enhanced the capacity of ISCs to promote tumors upon loss of Apc (Beyaz et al, 2016).…”

Section: Fatty Acid Oxidationmentioning

confidence: 99%

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Lipid Mediated Regulation of Adult Stem Cell Behavior

Clémot

Demarco

Jones

2020

Front. Cell Dev. Biol.

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Adult stem cells constitute an important reservoir of self-renewing progenitor cells and are crucial for maintaining tissue and organ homeostasis. The capacity of stem cells to self-renew or differentiate can be attributed to distinct metabolic states, and it is now becoming apparent that metabolism plays instructive roles in stem cell fate decisions. Lipids are an extremely vast class of biomolecules, with essential roles in energy homeostasis, membrane structure and signaling. Imbalances in lipid homeostasis can result in lipotoxicity, cell death and diseases, such as cardiovascular disease, insulin resistance and diabetes, autoimmune disorders and cancer. Therefore, understanding how lipid metabolism affects stem cell behavior offers promising perspectives for the development of novel approaches to control stem cell behavior either in vitro or in patients, by modulating lipid metabolic pathways pharmacologically or through diet. In this review, we will first address how recent progress in lipidomics has created new opportunities to uncover stem-cell specific lipidomes. In addition, genetic and/or pharmacological modulation of lipid metabolism have shown the involvement of specific pathways, such as fatty acid oxidation (FAO), in regulating adult stem cell behavior. We will describe and compare findings obtained in multiple stem cell models in order to provide an assessment on whether unique lipid metabolic pathways may commonly regulate stem cell behavior. We will then review characterized and potential molecular mechanisms through which lipids can affect stem cell-specific properties, including self-renewal, differentiation potential or interaction with the niche. Finally, we aim to summarize the current knowledge of how alterations in lipid homeostasis that occur as a consequence of changes in diet, aging or disease can impact stem cells and, consequently, tissue homeostasis and repair.

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Section: Fatty Acid Oxidationmentioning

confidence: 99%

Section: Fatty Acid Oxidationmentioning

confidence: 99%

Lipid Mediated Regulation of Adult Stem Cell Behavior

Clémot

Demarco

Jones

2020

Front. Cell Dev. Biol.

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“…Moreover, FMD cycles ameliorate or reverse disease progression in mouse models of multiple sclerosis (MS), and type I, and type II diabetes (Choi et al, 2016; Cheng et al, 2017). Recent studies also showed positive effects of a 24-hour fast on intestinal stem cell function in young and aged mice by a fatty acid oxidation pathway (Mihaylova et al, 2018). …”

Section: Introductionmentioning

confidence: 99%

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

et al. 2019

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SUMMARY Dietary interventions are potentially effective therapies for inflammatory bowel diseases (IBDs). We tested the effect of 4-day fasting-mimicking diet (FMD) cycles on a chronic dextran sodium sulfate (DSS)-induced murine model resulting in symptoms and pathology associated with IBD. These FMD cycles reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota, and reversed intestinal pathology caused by DSS, whereas water-only fasting increased regenerative and reduced inflammatory markers without reversing pathology. Transplants of Lactobacillus or fecal microbiota from DSS- and FMD-treated mice reversed DSS-induced colon shortening, reduced inflammation, and increased colonic stem cells. In a clinical trial, three FMD cycles reduced markers associated with systemic inflammation. The effect of FMD cycles on microbiota composition, immune cell profile, intestinal stem cell levels and the reversal of pathology associated with IBD in mice, and the anti-inflammatory effects demonstrated in a clinical trial show promise for FMD cycles to ameliorate IBD-associated inflammation in humans.

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“…Co., Ltd. Inc.). The sequences of Pck1 and Cpt1a primers were referred to a previous report 44,45 . The relative amounts of these mRNAs were normalized using the Actb mRNA signal.…”

Section: Gut Microbiome Analysis Of Japanese Long-distance Runnersmentioning

confidence: 99%

“…During exercise, subjects maintained a pedal speed of 60 rpm. RPE was measured with the Borg scale at baseline and at 10,20,30,40,45, and 50 min of exercise. In addition, a VAS questionnaire was used to assess fatigue after exercise testing (0, 30, 60 min).…”

Section: Human Study With Flaxseed Lignan or α-Cyclodextrin As Test Fmentioning

confidence: 99%

Bacteroides uniformis enhances endurance exercise performance through gluconeogenesis

Morita¹,

Kano²,

Ishii

et al. 2020

Preprint

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Athletes require high levels of energy to exercise under extreme conditions. Gut microbiota supplies energy to the host; however, the mechanism how gut microbiota contribute in the athlete is unclear. In this study, we determined that gut microbiota of Japanese long-distance runners differed from that of non-athletes, and the Bacteroides uniformis cell number in the feces correlated with 3,000-m race time. Mice administrated with B. uniformis extended the swimming time to exhaustion. Furthermore, acetate and propionate concentrations in the cecum increased in B. uniformis-administered mice subjected to weekly exercise.Expression levels of carnitine palmitoyl transferase 1a and phosphoenolpyruvate carboxykinase genes were elevated in the liver, suggesting that acetate and propionate produced by B. uniformis improve endurance exercise performance, at least in part, through enhancing gluconeogenesis. In addition, α-cyclodextrin administration increased B. uniformis and improved the performance in humans and mice, thus it is a candidate substance enhancing exercise performance through modification of gut microbiota. INTRODUCTIONHuman exercise performance comprises a combination of physical strength (e.g., muscle and explosive strength, endurance, and flexibility) and the actions performed in a given exercise (e.g., throwing, kicking, and hitting). Exercise performance can be improved through training; however, other factors, such as genetic background, may affect it. Recently, several reports have demonstrated that the gut microbiota contributes to health, energy homeostasis, and glucose and lipid metabolisms 1-4 . Hsu et al. reported that the swimming endurance time of germ-free mice was shorter than that of specific-pathogen-free mice and Bacteroides fragilis-monoassociated mice, thus identifying gut microbiota as one of the factors associated with exercise performance 5 . Conversely, other studies have shown that exercise changes the gut microbiome profile in mice 6,7 . In humans, Clarke et al. reported that the gut microbiota of rugby players had high α diversity and relative abundance of the genera Prevotella, Succinivibrio, Bacteroides, and Lactobacillus, as a difference to those of non-rugby players 8 . Another study on the gut microbiota of cyclists showed that a high abundance ofPrevotella was correlated with weekly exercise time 9 . However, none of these studies demonstrated a causal relationship between exercise performance and characteristic genera in the gut microbiota of athletes. Recently, Veillonella atypica, isolated from the gut microbiota of marathon runners, was shown to produce propionate from exercise-induced lactate in the gut, improving endurance exercise performance in mice 10 . Only that report has demonstrated a causal relationship between exercise performances and the gut microbiota in mice, but 3 detailed relationship remains unclear. In the present study, we investigated the role of Bacteroides uniformis, identified in the microbiome analysis of Japanese long-distance runners, in the en...

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Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Cited by 293 publications

References 59 publications

Lipid Mediated Regulation of Adult Stem Cell Behavior

Lipid Mediated Regulation of Adult Stem Cell Behavior

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

Bacteroides uniformis enhances endurance exercise performance through gluconeogenesis

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