Enhancement of differentiation of cultured adipogenic cells (TA1) by pertussis toxin

Shinohara, Osamu; Murata, Yoh-Ichi; Shimizu, Makoto

doi:10.1139/o92-100

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Suppression of adipogenesis by Ptx-sensitive GPCRs is well established (Hauner et al, 1994;Janke et al, 2002;Shinohara et al, 1992;Tomono et al, 2008;van Harmelen et al, 2008). As seen previously (Hauner et al, 1994) and in Figure 5, addition of Ptx to progenitor cells derived from human adipose tissues increases adipogenesis, suggesting tonic suppression of adipogenesis by Gi-linked receptors.…”

Section: Discussionsupporting

confidence: 72%

Arsenic Activates Endothelin-1 Gi Protein–Coupled Receptor Signaling to Inhibit Stem Cell Differentiation in Adipogenesis

Klei¹,

Garciafigueroa²,

Barchowsky³

2012

Toxicological Sciences

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Dysfunctional lipid and glucose metabolism contribute to metabolic syndrome-a major public health concern that enhances cardiovascular disease risk. Arsenic (As(III)) exposure may increase metabolic syndrome and cardiovascular disease risk by impairing adipose tissue differentiation, function, and insulin sensitivity through pathogenic mechanisms that remain unclear. We hypothesized that As(III) signals through the Pertussis toxin (Ptx) sensitive, Gi protein-coupled receptor (GPCR) to impair adipogenesis, as previously demonstrated for its stimulation of vascular oxidant generation, angiogenesis, and remodeling. Because both As(III) and GPCR ligands inhibit progenitor cell differentiation into adipocytes, we investigated the hypothesis in a model of low-passage human mesenchymal stem cells (hMSC). As(III) (0.1-1.0 µM) suppressed dexamethasone/insulin-induced hMSC adipogenesis, as indicated by decreased transcriptional promoters of differentiation, decreased fat droplet formation, and decreased expression of differentiated adipocyte markers, such as adiponectin and perilipin. Preincubating hMSC with Ptx prevented 90% of the suppressive effect of As(III). Selective competitive antagonists of Gi-coupled endothelin-1 type A and B receptors were ~60% effective in blocking As(III) inhibition and combination of antagonists to both receptors were 85% effective. In contrast, antagonists to the sphingosine-1-phosphate type 1 receptor (previously shown to mediate As(III) vascular effects) or the angiotensin II type 1 receptor were ineffective in blocking As(III) effects. These studies suggest a majority of arsenic-inhibited adipocyte differentiation, and metabolism requires endothelin-1 GPCRs and that As(III) effects on GPCR signaling are tissue and context specific. This may represent a significant mechanism for the contribution of arsenic exposure to increased metabolic and cardiovascular diseases.

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Section: Discussionsupporting

confidence: 72%

Arsenic Activates Endothelin-1 Gi Protein–Coupled Receptor Signaling to Inhibit Stem Cell Differentiation in Adipogenesis

Klei¹,

Garciafigueroa²,

Barchowsky³

2012

Toxicological Sciences

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“…This separation of pathways is similar to angiogenic and remodeling As(III) effects on endothelial cells being mediated by activation of S1PR1 receptors that is independent of As(III)-induced stress responses (Straub et al, 2009). Suppression of adipogenesis and adipose tissue maintenance by Ptx-sensitive Gi-coupled receptors is well established (Hauner et al, 1994;Janke et al, 2002;Shinohara et al, 1992;Tomono et al, 2008;van Harmelen et al, 2008). Gi-coupled receptors, such as AGTR1 (Elbaz et al, 2000;Janke et al, 2002) or EDNRA/EDNRB (Eriksson et al, 2009;van Harmelen et al, 2008) oppose increases in cAMP and block insulin signaling that suppresses lipolysis.…”

Section: Discussionmentioning

confidence: 81%

Arsenic-Stimulated Lipolysis and Adipose Remodeling Is Mediated by G-Protein-Coupled Receptors

Garciafigueroa

Klei

Ambrosio

et al. 2013

Toxicological Sciences

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Arsenic in drinking water promotes a number of diseases that may stem from dysfunctional adipose lipid and glucose metabolism. Arsenic inhibits adipocyte differentiation and promotes insulin resistance; however, little is known of the impacts of and mechanisms for arsenic effects on adipose lipid storage and lipolysis. Based on our earlier studies of arsenic-signaling mechanisms for vascular remodeling and inhibition of adipogenesis, we investigated the hypothesis that arsenic acts through specific adipocyte G-protein-coupled receptors (GPCRs) to promote lipolysis and decrease lipid storage. We first demonstrated that 5-week exposure of mice to 100 μg/l of arsenic in drinking water stimulated epididymal adipocyte hypertrophy, reduced the adipose tissue expression of perilipin (PLIN1, a lipid droplet coat protein), and increased perivascular ectopic fat deposition in skeletal muscle. Incubating adipocytes, differentiated from adipose-derived human mesenchymal stem cell, with arsenic stimulated lipolysis and decreased both Nile Red positive lipid droplets and PLIN1 expression. Arsenic-stimulated lipolysis was not associated with increased cAMP levels. However, preincubation of adipocytes with the Gi inhibitor, Pertussis toxin, attenuated As(III)-stimulated lipolysis and lipid droplet loss. Antagonizing Gi-coupled endothelin-1 type A and B receptors (EDNRA/EDNRB) also attenuated arsenic effects, but antagonizing other adipose Gi-coupled receptors that regulate fat metabolism was ineffective. The endothelin receptors have different roles in arsenic responses because only EDNRA inhibition prevented arsenic-stimulated lipolysis, but antagonists to either receptor protected lipid droplets and PLIN1 expression. These data support a role for specific GPCRs in arsenic signaling for aberrant lipid storage and metabolism that may contribute to the pathogenesis of metabolic disease caused by environmental arsenic exposures.

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“…Although the negative effect of PKC activation on differentiation (243,293,296,304). In studies on 3T3-F442A preadipocytes, modulation of adipogenesis by adipocyte differentiation appears well established, the role played by the different PKC isoforms in this process cAMP has been reported to depend on the increase in intracellular cAMP levels achieved by forskolin treatment; remains unsettled.…”

Section: Late Events and Terminal Differentiationmentioning

confidence: 99%

Understanding Adipocyte Differentiation

Gregoire

Smas

Sul

1998

Physiological Reviews

2,078

1,814

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The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiation. Growth and differentiation of preadipocytes is controlled by communication between individual cells or between cells and the extracellular environment. Various hormones and growth factors that affect adipocyte differentiation in a positive or negative manner have been identified. In addition, components involved in cell-cell or cell-matrix interactions such as preadipocyte factor-1 and extracellular matrix proteins are also pivotal in regulating the differentiation process. Identification of these molecules has yielded clues to the biochemical pathways that ultimately result in transcriptional activation via PPAR-gamma and C/EBP. Studies on the regulation of the these transcription factors and the mode of action of various agents that influence adipocyte differentiation will reveal the physiological and pathophysiological mechanisms underlying adipose tissue development.

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Enhancement of differentiation of cultured adipogenic cells (TA1) by pertussis toxin

Cited by 7 publications

References 31 publications

Arsenic Activates Endothelin-1 Gi Protein–Coupled Receptor Signaling to Inhibit Stem Cell Differentiation in Adipogenesis

Arsenic Activates Endothelin-1 Gi Protein–Coupled Receptor Signaling to Inhibit Stem Cell Differentiation in Adipogenesis

Arsenic-Stimulated Lipolysis and Adipose Remodeling Is Mediated by G-Protein-Coupled Receptors

Understanding Adipocyte Differentiation

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