scholarly journals Multi-omics Analysis of the Intermittent Fasting Response in Mice Identifies an Unexpected Role for HNF4α

Cell Reports ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 3566-3582.e4 ◽  
Author(s):  
Luke Hatchwell ◽  
Dylan J. Harney ◽  
Michelle Cielesh ◽  
Kieren Young ◽  
Yen Chin Koay ◽  
...  
2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Zhigang Liu ◽  
Tian Yuan ◽  
Xiaoshuang Dai ◽  
Lin Shi ◽  
Xuebo Liu

Abstract Objectives Cognitive decline is one of severe type 2 diabetes complications. Intermittent fasting (IF) is a promising dietary intervention for T2D risk reduction, but its protective effect and mechanism on diabetic cognitive dysfunction remain elusive. Gut microbiota plays a vital role interphasing diet and host physiology and pathology and highly affected by the dietary composition and patterns. It has been reported that the microbiota homeostasis is essential for maintenance of gut health and for modulating cognitive function. We hypothesized that gut microbiota might play a pivotal role in mediating protective effects of IF on diabetes-induced cognitive decline. Methods After a 28-day IF regimen treatment, cognitive behavioral tests and brain insulin signaling were assessed on db/db mice. The microbiota-metabolites-brain axis alterations were detected by multiple-omics analysis (transciptomics, 16S rRNA sequencing and metabolomics). A intergrade multi-omics analysis was performed to analyze the correlation among gut microbiota, plasma metabolites, and hippocampal gene expression. Results Here we found that a 28-day Intermittent fasting (IF) regimen improved cognitive deficits in db/db mice via a microbiota-metabolites-brain axis assessed by behavioral tests and multiple-omics analysis: IF activated AMPK/PGC1α signaling, enhanced mitochondrial biogenesis in hippocampus and elevated genes enriched in hippocampal metabolic function. Moreover, IF re-structured gut microbiota and improved plasma microbial metabolites in relation to diabetes and cognitive function, e.g., serotonin, 3-Indolepropionic acid, and bile acids. Integration of multi-omics data demonstrated strong links between IF-related genes, gut microbiome and metabolites. Furthermore, removal of gut microbiota with antibiotics partly abolished the observed benefits of IF on cognition and hippocampal metabolic function. Conclusions Taken together, the present study suggests a critical role of gut microbiota in connecting peripheral metabolism with brain function, which could lead to novel interventions against metabolism-implicated neurodegenerative pathophysiologies. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China.


2020 ◽  
Author(s):  
Jaswinder Singh Maras ◽  
Shvetank Sharma ◽  
Adil Bhat ◽  
sheetalnath Rooge ◽  
Reshu Agarwal ◽  
...  

2020 ◽  
Author(s):  
Lynda Grine ◽  
Niels Hilhorst ◽  
Nathalie Michels ◽  
Souheila Abbedou ◽  
Stefaan De Henauw ◽  
...  

BACKGROUND Psoriasis is a complex disease associated with multiple comorbidities, including metabolic syndrome and leaky gut syndrome. Dietary lifestyle interventions have been reported to affect the disease in terms of lesional severity. It remains unclear how diets affect these comorbidities and the general health in psoriasis patients. Modified Intermittent Fasting (MIF) on 2 non-consecutive days has shown beneficial effects on metabolic parameters. A significant advantage of MIF over the currently investigated dietary changes is its feasibility. OBJECTIVE Here, we aim to study the effects of MIF on skin, gut and metabolic health in psoriasis patients. METHODS A two-arm pilot prospective cross-over randomized control trial (RCT) will be performed in 20 patients with psoriasis as a pilot study. Patients will be randomized 1:1 to either start with MIF and subsequent regular diet for 12 weeks each or to start with regular diet and subsequent MIF for 12 weeks each. The following parameters will be assessed: demographics, disease phenotype, medical and familial history, psoriasis severity, dermatology-specific and general quality of life, nutritional and physical habits, mental and intestinal health, intestinal and cutaneous integrity, inflammatory and metabolic markers, and satisfaction. RESULTS The aim is to uncover the effects of MIF on psoriasis severity and gut health integrity through clinical and molecular investigation. More precisely, we want to map the evolution of the different markers in response to MIF as compared to the regular diet, such as psoriasis severity, permeability and inflammation. CONCLUSIONS Understanding how dietary lifestyles can affect epithelial lineages such as the skin and gut, will greatly improve our understanding on the development of psoriasis and may pose a non-pharmacological venue for treatments. CLINICALTRIAL ClinicalTrials.gov, NCT04418791. Registered June 5 2020, https://clinicaltrials.gov/ct2/show/NCT04418791. Current protocol date/version: May 20 2020


GeroScience ◽  
2021 ◽  
Author(s):  
Yoko O. Henderson ◽  
Nazmin Bithi ◽  
Christopher Link ◽  
Jie Yang ◽  
Rebecca Schugar ◽  
...  

AbstractGlobal average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.


2021 ◽  
Vol 10 (10) ◽  
pp. 2100
Author(s):  
Hiroshi Sakagami ◽  
Sachie Nakatani ◽  
Ayame Enomoto ◽  
Sana Ota ◽  
Miku Kaneko ◽  
...  

Efficient utilization of alkaline extracts of several plants for the treatment of oral diseases has been reported. To investigate the mechanism of anti-inflammatory activity of alkaline extract of the leaves of Sasa sp. (SE), multi-omics analysis using metabolomics and DNA array was performed. Human gingival fibroblasts (HGFs) were treated for IL-1β to induce inflammation (detected by PGE2 production in culture medium) in the presence or absence of SE. Both IL-1β and SE showed slight hormetic growth stimulation against HGF. SE inhibited PGE2 production dose- and time-dependently. Its inhibitory action was more pronounced by first treating the cells with SE, rather than with IL-1β. At 3 h after IL-1β treatment, 18 amino acids (except cysteine and glutamic acid), total glutathione (GSH, GSSG, Cys-GSH disulfide), Met-sulfoxide, 5-oxoproline, and SAM declined, whereas DNA expressions of AKT, CASP3, and CXCL3 were elevated. These changes were reversed by simultaneous treatment with SE. The present study suggests that the anti-inflammatory action of SE is mediated via various metabolic pathways for cell survival, apoptosis, and leukocyte recruitment.


2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie Henry-Barron ◽  
Diane Vizthum ◽  
...  

Abstract BACKGROUND There has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories<20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8. RESULTS 21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria. CONCLUSIONS The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.


Author(s):  
Mohammed Allaf ◽  
Hussein Elghazaly ◽  
Omer G Mohamed ◽  
Mohamed Firas Khan Fareen ◽  
Sadia Zaman ◽  
...  

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