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Adipocyte p53 coordinates the adipose tissue immune cell landscape upon intermittent fasting

ABSTRACT: In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, its fasting regimen-dependent regulation is unknown. Here, we show that cyclic intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, we provide evidence that this increase in LAM abundance is almost entirely dependent on p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation in AT during IF and increases the catabolic state of adipocytes, ameliorates metabolic flexibility, and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to long-term efficacy of a fasting-mimicking diet and that the expression of LAM markers and p53 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signaling in adipocytes dictates LAM accumulation in AT under IF and that adipocyte p53 modulates fasting effectiveness in mice and humans.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Adipocyte

SUBMITTER: riccardo zenezini chiozzi

LAB HEAD: Andreas Prokesch

PROVIDER: PXD041351 | Pride | 2024-01-16

REPOSITORIES: Pride

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Adipocyte p53 coordinates the adipose tissue immune cell landscape upon intermittent fasting

Project description:In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, its fasting regimen-dependent regulation is unknown. Here, we show that cyclic intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, we provide evidence that this increase in LAM abundance is almost entirely dependent on p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation in AT during IF and increases the catabolic state of adipocytes, ameliorates metabolic flexibility, and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to long-term efficacy of a fasting-mimicking diet and that the expression of LAM markers and p53 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signaling in adipocytes dictates LAM accumulation in AT under IF and that adipocyte p53 modulates fasting effectiveness in mice and humans.

2024-01-16 | GSE229690 | GEO

Bioactive decellularized extracellular matrix-based hydrogel supports human adipose tissue-derived stem cell maintenance and fibrocartilage phenotype

Project description:Decellularized extracellular matrix (dECM)-based hydrogels combined with hASCs could serve as an interface for studying behavior and differentiation properties in a cartilage microenvironment. In the present study, we described the behavior of hASCs cultured in a commercial dECM MatriXpec™. The protein composition of MatriXpec™ was accessed by mass spectrometry and is mainly represented by collagen proteins, building an hydrogel fibrous ultrastructure.

2023-12-22 | PXD047464 | Pride

Alterations in DNA methylation during three ex vivo stages of adipogenesis are linked to type 2 diabetes in obese patients

Project description:This study focused on identifying altered DNA methylation profiles in obese patients with diabetes, during three adipocyte differentiation stages. We isolated mesenchymal cells from obese patients with and without T2D to analyze DNA methylation profiles at 0, 3, and 18 days of ex vivo differentiation.

2021-11-03 | E-MTAB-10178 | biostudies-arrayexpress

Identification of Bmal1 binding sites by ChIP-seq in mouse lung tissue

Project description:Bmal1 ChIP-seq on C57/BL adult mouse lung tissue at Zeitgeber time ZT5.

2019-10-17 | E-MTAB-6354 | biostudies-arrayexpress

TP53 knock-down in cultured, starved human adipocytes

Project description:The goal of this cell culture experiment was to validate in vivo data showing adipocyte p53-dependent changes of the immune cell landscape of visceral adipose tissue in obese mice that are interemittently fasted.

2024-01-16 | GSE248893 | GEO

Computational drug repositioning identifies niclosamide and tribromsalan as inhibitors of Mycobacterium tuberculosis and Mycobacterium abscessus

Project description:Tuberculosis (TB) is still a major global health challenge, killing over 1.5 million people each year, and hence, there is a need to identify and develop novel treatments for Mycobacterium tuberculosis (M. tuberculosis). The prevalence of infections caused by nontuberculous mycobacteria (NTM) is also increasing and has overtaken TB cases in the United States and much of the developed world. Mycobacterium abscessus (M. abscessus) is one of the most frequently encountered NTM and is difficult to treat. We describe the use of drug-disease association using a semantic knowledge graph approach combined with machine learning models that has enabled the identification of several molecules for testing anti-mycobacterial activity. We established that niclosamide (M. tuberculosis IC90 2.95 μM; M. abscessus IC90 59.1 μM) and tribromsalan (M. tuberculosis IC90 76.92 μM; M. abscessus IC90 147.4 μM) inhibit M. tuberculosis and M. abscessus in vitro. To investigate the mode of action, we determined the transcriptional response of M. tuberculosis and M. abscessus to both compounds in axenic log phase, demonstrating a broad effect on gene expression that differed from known M. tuberculosis inhibitors. Both compounds elicited transcriptional responses indicative of respiratory pathway stress and the dysregulation of fatty acid metabolism. Further testing against drug-resistant isolates and other NTM is warranted to clarify the usefulness of these repurposed drugs for mycobacteria.

2024-03-01 | E-MTAB-13761 | biostudies-arrayexpress

Transcription profiling of mouse hair follicles in the 2nd telogen to anagen transition

Project description:Hair Follicle regeneration relies on both epithelial components (bulge and hair germ cells) and a mesenchymal one (dermal papilla cells). We used microarrays to detail the global programme of gene expression underlying organ regeneration at the transition between quiescent stages (early and middle telogen) and the initiation of a new growth (late telogen). Experiment Overall Design: These microarray at the 3 different stages were designed to identify signals released by the mesenchymal dermal papilla cells to activate epithelial growth, their target genes in the hair germ and bulge compartments, and to get at gene signature differences and similarities between hair germ and bulge cells.

2009-03-25 | E-GEOD-15185 | biostudies-arrayexpress

The Obese Adipocyte

Project description:The Obese Adipocyte

| PRJNA575203 | ENA

Toxoplasma gondii MOB1 interactome

Project description:MOB1 is a conserved protein that regulates cellular proliferation versus apoptosis, centrosome duplication and cellular differentiation in multicellular eukaryotes and also cytokinesis and division axis orientation in unicellular and multicellular eukaryotes. Toxoplasma gondii, an obligate intracellular parasite of veterinary and medical importance, presents one MOB1 protein. T. gondii interconverts between several cellular stages during its life cycle, namely between fast replicating tachyzoite and slow replicating bradyzoite stages during its asexual cycle, a key ability for its success as a parasite. Bradyzoites produce tissue cysts, establishing a chronic infection that enables recrudescence. Conversion is dependent on cell cycle regulation and involves cell differentiation and regulation of replication. This led us to select MOB1 as a strong candidate to be involved in the Toxoplasma replication process. To elucidate how MOB1 acts in T. gondii, we employed a proximity biotinylation method and identified the MOB1 interactome. Toxoplasma gondii RH tachyzoites were transfected with BirA containing plasmid vectors for random integration and two strains were isolated. The control strain expresses a FLAG-BirA recombinant protein while the test strain expresses a FLAG-BirA-MOB1 recombinant protein. Biotinylated proteins were purified using streptavidin-agarose beads. The purified proteins were trypsinized and analyzed by nanoLC-MS/MS.

2022-02-16 | PXD028781 | Pride

Project description:Temporal lobe epilepsy (TLE) is the most common subtype of epilepsy in adults and is characterized by neuronal loss, gliosis, and sprouting mossy fibers in the hippocampus. But the mechanism underlying neuronal loss has not been fully elucidated. A new programmed cell death, cuproptosis, has recently been discovered; however, its role in TLE is not clear. To investigate the the features of 12 cuproptosis-related genes in TLEs and controls，six epileptic focus specimens were obtained from the hippocampus of patients diagnosed with intractable TLE according to the International League Against Epilepsy (ILAE) diagnostic criteria (Blümcke et al., 2013). Because the hippocampal specimens from age matched controls were sparse, we only collected two control hippocampi from autopsied individuals without a known history of neurologic or psychiatric disease, ensuring a 3:1 disease-to control match.

2023-06-20 | E-MTAB-13092 | biostudies-arrayexpress

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