PRDM16 sustains white fat gene expression profile in human adipocytes in direct relation with insulin action

Moreno-Navarrete, José María; Ortega, Francisco; Moreno, María; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel

doi:10.1016/j.mce.2015.01.042

Cited by 11 publications

(11 citation statements)

References 43 publications

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“…In the converted exBAT, UCP1 mRNA levels were preferentially upregulated, while DIO2, leptin, and PRDM16 mRNA levels were downregulated (Fig. 4b ), concordant with previous reports of human tissues in vitro 53 . Accordingly, UCP1 protein content (Fig.…”

Section: Resultssupporting

confidence: 92%

A direct tissue-grafting approach to increasing endogenous brown fat

Blumenfeld

Kang

Fenzl

et al. 2018

Sci Rep

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There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re-implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches. With this process, entitled “exBAT”, we identified conditions, in both mouse and human tissue, that convert whole fragments of WAT to BAT via a single step and without unwanted off-target pharmacological effects. We show that ex vivo, exBAT exhibited UCP1 immunostaining, lipid droplet formation, and mitochondrial metabolic activity consistent with native BAT. In mice, exBAT exhibited a highly durable phenotype for at least 8 weeks. Overall, these results enable a simple and scalable tissue-grafting strategy, rather than pharmacological approaches, for increasing endogenous BAT and studying its effect on host weight and metabolism.

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Section: Resultssupporting

confidence: 92%

A direct tissue-grafting approach to increasing endogenous brown fat

Blumenfeld

Kang

Fenzl

et al. 2018

Sci Rep

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“…RNA purification, gene expression procedures, and analyses were carried out, as previously described . Briefly, RNA purification was performed using the RNeasy Lipid Tissue Mini Kit (Qiagen, Izasa SA, Barcelona, Spain) and the integrity was checked by the Agilent Bioanalyzer (Agilent Technologies, Palo Alto, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Gene expression was assessed by real‐time PCR using a LightCycler® 480 Real‐Time PCR System (Roche Diagnostics SL, Barcelona, Spain), using TaqMan® technology suitable for relative genetic expression quantification. The commercially available and pre‐validated TaqMan® primer/probe sets used were detailed elsewhere …”

Section: Methodsmentioning

confidence: 99%

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Gut Microbiota Interacts with Markers of Adipose Tissue Browning, Insulin Action and Plasma Acetate in Morbid Obesity

Moreno-Navarrete

Sérino

Blasco-Baqué

et al. 2017

Molecular Nutrition Food Res

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“…This change in DNA methylation was, nevertheless, not reflected by significant changes in gene expression (although there was a trend for downregulation) (Supplementary Figure S4), possibly because of the small sample size used. PRMD16 is a transcription factor that activates brown fatspecific genes and is also associated with insulin sensitivity in obese subjects, linking adipose tissue expression and systemic metabolic homeostasis [36]. The gene expression analysis revealed significantly lower expression of PRDM16 both in hASCs and PBMCs from patients relative to controls.…”

Section: Differentially Methylated Positions In Patients With Crohn'smentioning

confidence: 96%

Adipose stem cells from patients with Crohn’s disease show a distinctive DNA methylation pattern

et al. 2020

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Background: Crohn's disease (CD) is characterized by persistent inflammation and ulceration of the small or large bowel, and expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-derived stem cells (hASCs) from CF of patients with CD exhibit dysfunctional phenotypes, including a pro-inflammatory profile, high phagocytic capacity, and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission and are found in all adipose depots explored including subcutaneous fat. We hypothesized that changes in hASCs are a consequence of epigenetic modifications. Methods: We applied epigenome-wide profiling with a methylation array (Illumina EPIC/850k array) and gene expression analysis to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat of patients with CD and healthy controls (n = 7 and 5, respectively; cohort I). Differentially methylated positions (p value cutoff < 1 × 10 −4 and ten or more DMPs per gene) and regions (inclusion threshold 0.2, p value cutoff < 1 × 10 −2 and more than 2 DMRs per gene) were identified using dmpfinder and Bumphunter (minfi), respectively. Changes in the expression of differentially methylated genes in hASCs were validated in a second cohort (n = 10/10 inactive and active CD and 10 controls; including patients from cohort I) and also in peripheral blood mononuclear cells (PBMCs) of patients with active/inactive CD and of healthy controls (cohort III; n = 30 independent subjects). Results: We found a distinct DNA methylation landscape in hASCs from patients with CD, leading to changes in the expression of differentially methylated genes involved in immune response, metabolic, cell differentiation, and development processes. Notably, the expression of several of these genes in hASCs and PBMCs such as tumor necrosis factor alpha (TNFA) and PR domain zinc finger protein 16 (PRDM16) were not restored to normal (healthy) levels after disease remission. Conclusions: hASCs of patients with CD exhibit a unique DNA methylation and gene expression profile, but the expression of several genes are only partially restored in patients with inactive CD, both in hASCs and PBMCs. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.

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PRDM16 sustains white fat gene expression profile in human adipocytes in direct relation with insulin action

Cited by 11 publications

References 43 publications

A direct tissue-grafting approach to increasing endogenous brown fat

A direct tissue-grafting approach to increasing endogenous brown fat

Gut Microbiota Interacts with Markers of Adipose Tissue Browning, Insulin Action and Plasma Acetate in Morbid Obesity

Adipose stem cells from patients with Crohn’s disease show a distinctive DNA methylation pattern

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