Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

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

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Reduced High-Dose Radiation-Induced Residual Genotoxic Damage by Induction of Radioadaptive Response and Prophylactic Mild Dietary Restriction in Mice

Dose-Response ◽

10.1177/1559325820982166 ◽

2021 ◽

Vol 19 (1) ◽

pp. 155932582098216

Author(s):

Bing Wang ◽

Kaoru Tanaka ◽

Takanori Katsube ◽

Kouichi Maruyama ◽

Yasuharu Ninomiya ◽

...

Keyword(s):

Dietary Restriction ◽

High Dose ◽

Cancer Treatments ◽

Hematopoietic Stem ◽

Beneficial Effects ◽

Radiation Induced ◽

Potential Strategy ◽

Higher Doses

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

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Intermittent Fasting–Dietary Restriction as a Biological Hormetin for Health Benefits

The Science of Hormesis in Health and Longevity ◽

10.1016/b978-0-12-814253-0.00008-5 ◽

2019 ◽

pp. 99-104

Author(s):

Anuradha Sharma ◽

Taranjeet Kaur ◽

Harpal Singh ◽

Gurcharan Kaur

Keyword(s):

Dietary Restriction ◽

Health Benefits ◽

Intermittent Fasting

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Drosophila Gut—A Nexus Between Dietary Restriction and Lifespan

International Journal of Molecular Sciences ◽

10.3390/ijms19123810 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3810 ◽

Cited By ~ 3

Author(s):

Ting Lian ◽

Qi Wu ◽

Brian Hodge ◽

Kenneth Wilson ◽

Guixiang Yu ◽

...

Keyword(s):

Digestive Tract ◽

Dietary Restriction ◽

Healthy Aging ◽

Fat Body ◽

Critical Role ◽

Vital Role ◽

Intestinal Epithelial ◽

Beneficial Effects ◽

Accumulation Of Damage

Aging is often defined as the accumulation of damage at the molecular and cellular levels which, over time, results in marked physiological impairments throughout the organism. Dietary restriction (DR) has been recognized as one of the strongest lifespan extending therapies observed in a wide array of organisms. Recent studies aimed at elucidating how DR promotes healthy aging have demonstrated a vital role of the digestive tract in mediating the beneficial effects of DR. Here, we review how dietary restriction influences gut metabolic homeostasis and immune function. Our discussion is focused on studies of the Drosophila digestive tract, where we describe in detail the potential mechanisms in which DR enhances maintenance of the intestinal epithelial barrier, up-regulates lipid metabolic processes, and improves the ability of the gut to deal with damage or stress. We also examine evidence of a tissue-tissue crosstalk between gut and neighboring organs including brain and fat body. Taken together, we argue that the Drosophila gut plays a critical role in DR-mediated lifespan extension.

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GLP-1 and Adiponectin: Effect of Weight Loss After Dietary Restriction and Gastric Bypass in Morbidly Obese Patients with Normal and Abnormal Glucose Metabolism

Obesity Surgery ◽

10.1007/s11695-008-9678-5 ◽

2008 ◽

Vol 19 (3) ◽

pp. 313-320 ◽

Cited By ~ 45

Author(s):

Camila Puzzi de Carvalho ◽

Daniela Miguel Marin ◽

Aglécio Luiz de Souza ◽

José Carlos Pareja ◽

Elintom Adami Chaim ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Glucose Metabolism ◽

Dietary Restriction ◽

Morbidly Obese ◽

Obese Patients ◽

Abnormal Glucose Metabolism

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GLP-1-mediated delivery of the PPAR𝛼/𝛾 dual-agonist Tesaglitazar improves obesity and glucose metabolism in mice

10.21203/rs.3.rs-1081959/v1 ◽

2021 ◽

Author(s):

Carmelo Quarta ◽

Kerstin Stemmer ◽

Aaron Novikoff ◽

Bin Yang ◽

Felix Klingelhuber ◽

...

Keyword(s):

Body Weight ◽

Glucose Metabolism ◽

Peroxisome Proliferator ◽

Protein Targets ◽

Beneficial Effects ◽

Glucose And Lipid Metabolism ◽

Therapeutic Value ◽

Affect Body Weight ◽

Peroxisome Proliferator Activated Receptors ◽

Dual Agonist

Abstract Dual-agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPAR𝛼/𝛾) have shown beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to unfavorable cardiovascular and/or renal effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPAR𝛼/𝛾 dual-agonist Tesaglitazar to GLP-1 to allow for the GLP-1 receptor-dependent delivery of Tesaglitazar. GLP-1/Tesaglitazar does not differ from matched GLP-1 in GLP-1R signaling, but shows GLP-1R-dependent PPAR𝛾-RXR heterodimerization with enhanced efficacy to improve body weight, food intake, and glucose metabolism relative to GLP-1 or Tesaglitazar in mice with diet- and genetically-induced obesity. The conjugate fails to affect body weight and glucose metabolism in GLP-1R knockout (ko) mice and shows preserved effects in DIO mice at doses subthreshold for GLP-1 and Tesaglitazar to improve metabolism. Consistent with the GLP-1R expression pattern, LC/MS-based proteomics identified a series of novel PPAR protein targets in the hypothalamus that are acutely upregulated by Tesaglitazar and by GLP-1/Tesaglitazar, but not by treatment with GLP-1. Collectively, our data show that GLP-1/Tesaglitazar improves energy and glucose metabolism with superior efficacy to GLP-1 or Tesaglitazar alone and suggest that this conjugate holds therapeutic value to treat hyperglycemia and insulin resistance.

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In Contrast to Dietary Restriction, Application of Resveratrol in Mice Does not Alter Mouse Major Urinary Protein Expression

Nutrients ◽

10.3390/nu12030815 ◽

2020 ◽

Vol 12 (3) ◽

pp. 815 ◽

Cited By ~ 1

Author(s):

Kathrin Pallauf ◽

Ilka Günther ◽

Dawn Chin ◽

Gerald Rimbach

Keyword(s):

Protein Expression ◽

Dietary Restriction ◽

Model Organisms ◽

Mrna Levels ◽

Urinary Proteins ◽

Pheromone Communication ◽

Beneficial Effects ◽

Major Urinary Proteins ◽

Glucocorticoid Response ◽

Glucocorticoid Response Elements

Resveratrol (RSV) supplementation in mice has been discussed as partly mimicking the beneficial effects of dietary restriction (DR). However, data on putative benefits from resveratrol application in mice and other model organisms including humans is contradictory. Mouse major urinary proteins (MUPs) are a family of proteins that are expressed in rodent liver and secreted via urine. Impacting (mating) behavior and pheromone communication, they are severely down-regulated upon DR. We carried out two studies in C57BL/6Rj mice where RSV was either supplemented via diet or injected intraperitoneally for 8 weeks. Contrary to −40% DR, RSV did not decrease total MUP protein expression or Mup (amongst others Mup3, Mup5, Mup6, Mup15, and Mup20) mRNA levels in mouse liver when compared to ad-libitum (AL)-fed controls. Since inhibitory glucocorticoid response elements can be found in Mup promoters, we also measured glucocorticoid receptor (GR) levels in nuclear hepatic extracts. Consistent with differential MUP expression, we observed more nuclear GR in DR mice than in RSV-supplemented and AL control mice with no difference between RSV and AL. These findings point to the notion that, in mice, RSV does not mimic DR in terms of differential MUP expression.

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