Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling

AbstractAdipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations: Dpp4+ stem-like cells, Aoc3+ pre-adipocyte-like cells, and the enigmatic CD142+ cells. A great challenge now is to functionally characterize these distinct ASPC populations. Here, we focus on CD142+ ASPCs since discrepant properties have been assigned to this subpopulation, from adipogenic to non- and even anti-adipogenic. To address these inconsistencies, we comprehensively characterized mammalian subcutaneous CD142+ ASPCs across various sampling conditions. Our findings demonstrate that CD142+ ASPCs exhibit high molecular and phenotypic robustness, firmly supporting their non- and anti-adipogenic properties. However, these properties emerge in an age-dependent manner, revealing surprising temporal CD142+ ASPC behavioural alterations. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142− ASPCs into a non-adipogenic, Areg-like one.

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Retinoic acid receptor γ 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes

Biochemical Journal ◽

10.1042/bj2930807 ◽

1993 ◽

Vol 293 (3) ◽

pp. 807-812 ◽

Cited By ~ 30

Author(s):

Y Kamei ◽

T Kawada ◽

R Kazuki ◽

E Sugimoto

Keyword(s):

Adipose Tissue ◽

Retinoic Acid ◽

Mrna Expression ◽

De Novo ◽

Retinoic Acid Receptor ◽

Mrna Level ◽

Fold Increase ◽

Dependent Manner ◽

Alpha Beta ◽

Rat Adipose Tissue

Retinoids, especially all-trans retinoic acid (RA), have been shown to inhibit the differentiation of preadipose cells. In the present study, the expression of retinoic acid receptors (RAR alpha, beta and gamma) and retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in rat adipose tissue and mouse 3T3-L1 adipose cells. The adipose tissue and/or 3T3-L1 cells expressed mRNAs for a number of nuclear retinoid receptors, including RAR alpha, beta and gamma, and RXR alpha, beta and gamma. RAR alpha, RAR gamma, RXR alpha and RXR beta mRNAs were abundant in adipose tissue and 3T3-L1 cells. RXR gamma mRNA was detected in adipose tissue but not in 3T3-L1 cells. Treatment of 3T3-L1 cells with 1 microM RA led to a 4-5-fold increase in the RAR gamma mRNA level, but only a trace amount of RAR beta mRNA was detected. RAR gamma mRNA expression was rapidly (within 2 h) induced by physiological concentrations of RA in a dose-dependent manner. The response of RAR gamma mRNA expression to RA was reversible; rapid disappearance of RAR gamma mRNA occurred on RA removal. In addition, the induction of RAR gamma expression did not require de novo protein synthesis, but was completely abolished by an inhibitor of RNA synthesis. Using RAR gamma 1 and gamma 2 isoform-specific probes, the patterns of RAR gamma 1 and gamma 2 mRNA expression in 3T3-L1 cells in the presence and absence of RA were examined. RAR gamma 1 mRNA was detected in 3T3-L1 cells but was not affected by RA treatment; however, RAR gamma 2 mRNA was strongly induced by RA.

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Faculty Opinions recommendation of Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11635956.12696054 ◽

2011 ◽

Author(s):

Humphrey Yao ◽

Chang Liu

Keyword(s):

Retinoic Acid ◽

Retinoic Acid Signalling ◽

Meiotic Entry

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Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

Nature Communications ◽

10.1038/s41467-021-22579-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Anastasia Georgiadi ◽

Valeria Lopez-Salazar ◽

Rabih El- Merahbi ◽

Rhoda Anane Karikari ◽

Xiaochuan Ma ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Dependent Manner ◽

Metabolic Dysfunction ◽

Functional Interaction ◽

White Adipocyte ◽

White Adipocytes ◽

Obesity And Diabetes ◽

Adhesion Gpcr ◽

Circulating Levels

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

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Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue

Scientific Reports ◽

10.1038/s41598-021-92711-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jie Qu ◽

Sarah Fourman ◽

Maureen Fitzgerald ◽

Min Liu ◽

Supna Nair ◽

...

Keyword(s):

Adipose Tissue ◽

Glucose Uptake ◽

Molecular Mechanisms ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Receptor ◽

Dependent Manner ◽

Related Protein ◽

Density Lipoprotein Receptor ◽

Lipoprotein Receptor Related Protein

AbstractApolipoprotein A4 (APOA4) is one of the most abundant and versatile apolipoproteins facilitating lipid transport and metabolism. APOA4 is synthesized in the small intestine, packaged onto chylomicrons, secreted into intestinal lymph and transported via circulation to several tissues, including adipose. Since its discovery nearly 4 decades ago, to date, only platelet integrin αIIbβ3 has been identified as APOA4 receptor in the plasma. Using co-immunoprecipitation coupled with mass spectrometry, we probed the APOA4 interactome in mouse gonadal fat tissue, where ApoA4 gene is not transcribed but APOA4 protein is abundant. We demonstrate that lipoprotein receptor-related protein 1 (LRP1) is the cognate receptor for APOA4 in adipose tissue. LRP1 colocalized with APOA4 in adipocytes; it interacted with APOA4 under fasting condition and their interaction was enhanced during lipid feeding concomitant with increased APOA4 levels in plasma. In 3T3-L1 mature adipocytes, APOA4 promoted glucose uptake both in absence and presence of insulin in a dose-dependent manner. Knockdown of LRP1 abrogated APOA4-induced glucose uptake as well as activation of phosphatidylinositol 3 kinase (PI3K)-mediated protein kinase B (AKT). Taken together, we identified LRP1 as a novel receptor for APOA4 in promoting glucose uptake. Considering both APOA4 and LRP1 are multifunctional players in lipid and glucose metabolism, our finding opens up a door to better understand the molecular mechanisms along APOA4-LRP1 axis, whose dysregulation leads to obesity, cardiovascular disease, and diabetes.

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Second-trimester maternal lipid profiles predict pregnancy complications in an age-dependent manner

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-019-05094-z ◽

2019 ◽

Vol 299 (5) ◽

pp. 1253-1260 ◽

Cited By ~ 1

Author(s):

Qi Wu ◽

Lixia Zhang ◽

Licong Huang ◽

Yu Lei ◽

Lin Chen ◽

...

Keyword(s):

Pregnancy Complications ◽

Lipid Profiles ◽

Dependent Manner ◽

Second Trimester ◽

Age Dependent

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Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model

Biochemical Society Transactions ◽

10.1042/bst0381001 ◽

2010 ◽

Vol 38 (4) ◽

pp. 1001-1005 ◽

Cited By ~ 14

Author(s):

Kunie Ando ◽

Karelle Leroy ◽

Céline Heraud ◽

Anna Kabova ◽

Zehra Yilmaz ◽

...

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

Double Mutant ◽

Transgenic Mouse Model ◽

Tau Proteins ◽

Dependent Manner ◽

Age Dependent ◽

Ad Alzheimer’S Disease ◽

Tau Aggregation ◽

The Brain

We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30×TauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30×TauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.

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Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

Cellular Physiology and Biochemistry ◽

10.1159/000481876 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1449-1459 ◽

Cited By ~ 4

Author(s):

Renata A. C. Silva ◽

Andréa F. Gonçalves ◽

Priscila P. dos Santos ◽

Bruna Rafacho ◽

Renan F. T. Claro ◽

...

Keyword(s):

Oxidative Stress ◽

Retinoic Acid ◽

Energy Metabolism ◽

Cardiac Remodeling ◽

Citrate Synthase ◽

Isolated Heart ◽

Lipid Hydroperoxide ◽

Dependent Manner ◽

Heart Study ◽

Dose Dependent

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

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Combination of red and blue light induces anthocyanin and other secondary metabolite biosynthesis pathways in an age-dependent manner in Batavia lettuce

Plant Science ◽

10.1016/j.plantsci.2021.110977 ◽

2021 ◽

pp. 110977

Author(s):

Benny Jian Rong Sng ◽

Bonggyu Mun ◽

Bijayalaxmi Mohanty ◽

Mijung Kim ◽

Zhi Wei Phua ◽

...

Keyword(s):

Secondary Metabolite ◽

Blue Light ◽

Dependent Manner ◽

Secondary Metabolite Biosynthesis ◽

Age Dependent

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Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice

Communications Biology ◽

10.1038/s42003-021-02204-z ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

James Moore ◽

Rashid Akbergenov ◽

Martina Nigri ◽

Patricia Isnard-Petit ◽

Amandine Grimm ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Atrophy ◽

Strength Analysis ◽

Dependent Manner ◽

Random Errors ◽

Age Related ◽

Related Phenotype ◽

Age Dependent ◽

Translation Accuracy ◽

Transcriptomic Changes

AbstractRandom errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.

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