The transcriptional co-activator PGC-1α up regulates apelin in human and mouse adipocytes

Abstract The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.

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Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity

Endocrinology ◽

10.1210/en.2004-1427 ◽

2005 ◽

Vol 146 (4) ◽

pp. 1764-1771 ◽

Cited By ~ 514

Author(s):

Jérémie Boucher ◽

Bernard Masri ◽

Danièle Daviaud ◽

Stéphane Gesta ◽

Charlotte Guigné ◽

...

Keyword(s):

Adipose Tissue ◽

Cell Types ◽

Fat Cells ◽

Mrna Levels ◽

Blood Concentrations ◽

Brown Adipose ◽

Main Determinants ◽

Differentiation Stage ◽

Mouse Adipocytes ◽

Human And Mouse

Abstract The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.

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Abstract 009: CETP inhibitors Torcetrapib, Dalcetrapib, and Anacetrapib induce adipocyte-derived Aldosterone production through Nox and STAT3 activation

Hypertension ◽

10.1161/hyp.64.suppl_1.009 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Francisco J Rios ◽

Karla B Neves ◽

Aurelie Nguyen Dinh Cat ◽

Sarah Even ◽

Roberto Palacios ◽

...

Keyword(s):

Clinical Trials ◽

Cetp Inhibitors ◽

Amplex Red ◽

Mitochondrial Ros ◽

Stat3 Phosphorylation ◽

Aldosterone Production ◽

Ros Scavenger ◽

Mouse Adipocytes ◽

Human And Mouse

Large clinical trials indicated that CETP inhibitors increase HDL levels, but had unexpected side effects, such as hyperaldosteronism and hypertension. Some CETP inhibitors appear to accumulate in adipocytes, which are a source of aldosterone (Aldo). As such, we questioned whether CETP inhibitors influence Aldo production in adipocytes and assessed the role of reactive oxygen species (ROS) and STAT3 in this process. Human adipocytes (SW872), expressing CETP, were studied and compared to mouse adipocytes (3T3-L1), lacking CETP. Cells were treated with torcetrapib (TOR), dalcetrapib (DAL), or anacetrapib (ANA). To evaluate the role of ROS, cells were pre-treated with N-acetylcystein (NAC-ROS scavenger), ML171 and GKT136901 (Nox1/4 inhibitor, respectively), and Rotenone (Rot, mitochondrial ROS inhibitor). ROS were measured by lucigenin and amplex red. Aldo production, measured by ELISA, was induced by TOR (668pg/mL), DAL (348pg/mL) and ANA (434pg/mL) (p<0.05 vs control 196pg/mL); an effect blocked by NAC. TOR, DAL and ANA increased superoxide (2-fold) and H2O2 (1.5-fold) production, and STAT3 phosphorylation (p<0.05). TOR increased Nox1, 4 and 5 (2-fold); DAL increased Nox4 (2-fold) and, ANA increased Nox1 and 4 (3-fold). In TOR treated cells, Aldo production was inhibited by GKT (62%), ML171 (62%), Rot (45%), and S3I-201 (STAT3 inhibitor, 66%). DAL-induced Aldo production was blocked by ML171(62%) and S3I-201 (74%). In ANA treated cells, Aldo production was inhibited by GKT (94%), ML171 (83%), and Rot (66%). We also assessed effects of CETP inhibitors on chemerin production, a novel adipokine associated with hypertension. TOR, but not ANA or DAL stimulated chemerin production (331pg/mL vs control 154pg/mL p<0.05); an effect blocked by GKT (95%) and S3I-201 (100%). In mouse adipocytes, TOR, DAL, and ANA induced Aldo (453pg/mL, 375pg/mL, and 445pg/mL vs cont 253pg/mL, p<0.05) and ROS production (1.7-fold, p<0.05). In conclusion, CETP inbitors induced aldosterone production in human and mouse adipocytes through redox-related mechanisms involving STAT3, Noxs and mitochondria. These novel findings have important clinical significance and may explain, in part, the hyperaldosteronism and hypertension reported in CETP clinical trials.

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Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes

Stem Cell Reports ◽

10.1016/j.stemcr.2020.03.002 ◽

2020 ◽

Vol 14 (4) ◽

pp. 590-602

Author(s):

Max Friesen ◽

Curtis R. Warren ◽

Haojie Yu ◽

Takafumi Toyohara ◽

Qiurong Ding ◽

...

Keyword(s):

Mouse Adipocytes ◽

Human And Mouse

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FOSL2 promotes leptin gene expression in human and mouse adipocytes

Journal of Clinical Investigation ◽

10.1172/jci58431 ◽

2012 ◽

Vol 122 (3) ◽

pp. 1010-1021 ◽

Cited By ~ 45

Author(s):

Christiane D. Wrann ◽

Jun Eguchi ◽

Aline Bozec ◽

Zhao Xu ◽

Tarjei Mikkelsen ◽

...

Keyword(s):

Gene Expression ◽

Mouse Adipocytes ◽

Human And Mouse

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Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting MAPK signalling

Biochemical Journal ◽

10.1042/bj20150019 ◽

2015 ◽

Vol 472 (3) ◽

pp. 309-318 ◽

Cited By ~ 11

Author(s):

Fang Guo ◽

Hui He ◽

Zhi-Chao Fu ◽

Shengping Huang ◽

Tingtao Chen ◽

...

Keyword(s):

Protein Kinase ◽

Macrophage Activation ◽

Mitogen Activated Protein Kinase ◽

Secreted Protein ◽

Adipose Tissues ◽

Mapk Signalling Pathway ◽

Mapk Signalling ◽

Mitogen Activated Protein ◽

Mouse Adipocytes ◽

Human And Mouse

The study identified a novel secreted protein PRX-like 2 activated in M-CSF-stimulated monocytes (PAMM) from human and mouse adipocytes. The adipocyte-derived PAMM suppresses macrophage activation by inhibiting mitogen-activated protein kinase (MAPK) signalling pathway, which may represent a novel mechanism to resolve the chronic inflammation in the obese adipose tissues.

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Some Structural Features of Metaphase Chromosomes of Mice and Men

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060969 ◽

1967 ◽

Vol 25 ◽

pp. 190-191

Author(s):

Godfrey C. Hoskins ◽

Betty B. Hoskins

Keyword(s):

Electron Microscopy ◽

Electron Micrographs ◽

Structural Features ◽

Metaphase Chromosomes ◽

The Future ◽

Of Mice And Men ◽

Mouse Cells ◽

Human And Mouse

Metaphase chromosomes from human and mouse cells in vitro are isolated by micrurgy, fixed, and placed on grids for electron microscopy. Interpretations of electron micrographs by current methods indicate the following structural features.Chromosomal spindle fibrils about 200Å thick form fascicles about 600Å thick, wrapped by dense spiraling fibrils (DSF) less than 100Å thick as they near the kinomere. Such a fascicle joins the future daughter kinomere of each metaphase chromatid with those of adjacent non-homologous chromatids to either side. Thus, four fascicles (SF, 1-4) attach to each metaphase kinomere (K). It is thought that fascicles extend from the kinomere poleward, fray out to let chromosomal fibrils act as traction fibrils against polar fibrils, then regroup to join the adjacent kinomere.

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Binucleate Spermiogenesis in the Mouse

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010009381x ◽

1972 ◽

Vol 30 ◽

pp. 112-113

Author(s):

John J. Wolosewick

Keyword(s):

Electron Microscopy ◽

Phosphate Buffer ◽

Seminiferous Epithelium ◽

Mouse Testis ◽

Germinal Epithelium ◽

Intercellular Bridges ◽

Adult Mice ◽

Cervical Dislocation ◽

Human And Mouse

Classically, the male germinal epithelium is depicted as synchronously developing uninucleate spermatids conjoined by intercellular bridges. Recently, binucleate and multinucleate spermatids from human and mouse testis have been reported. The present paper describes certain developmental events in one type of binucleate spermatid in the seminiferous epithelium of the mouse.Testes of adult mice (ABP Jax) were removed from the animals after cervical dislocation and placed into 2.5% glutaraldehyde/Millonig's phosphate buffer (pH 7.2). Testicular capsules were gently split and separated, exposing the tubules. After 15 minutes the tissue was carefully cut into cubes (approx. 1mm), fixed for an additional 45 minutes and processed for electron microscopy.

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