Activin A plays a critical role in proliferation and differentiation of human adipose progenitors

Laure Emmanuelle Zaragosi, Brigitte Wdziekonski, Phi Villageois, Mayoura Keophiphath, Marie Maumus, Tamara Tchkonia, Virginie Bourlier, Tala Mohsen-Kanson, Annie Ladoux, Christian Elabd, Marcel Scheideler, Zlatko Trajanoski, Yasuhiro Takashima, Ez Zoubir Amri, Daniele Lacasa, Coralie Sengenes, Gérard Ailhaud, Karine Clément, Anne Bouloumie, James L KirklandChristian Dani

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - Growth of white adipose tissue takes place in normal development and in obesity. A pool of adipose progenitors is responsible for the formation of new adipocytes and for the potential of this tissue to expand in response to chronic energy overload. However, factors controlling self-renewal of human adipose progenitors are largely unknown. We investigated the expression profile and the role of activin A in this process. RESEARCH DESIGN AND METHODS - Expression of INHBA/activin A was investigated in three types of human adipose progenitors. We then analyzed at the molecular level the function of activin A during human adipogenesis. We finally investigated the status of activin A in adipose tissues of lean and obese subjects and analyzed macrophage-induced regulation of its expression. RESULTS - INHBA/activin A is expressed by adipose progenitors from various fat depots, and its expression dramatically decreases as progenitors differentiate into adipocytes. Activin A regulates the number of undifferentiated progenitors. Sustained activation or inhibition of the activin A pathway impairs or promotes, respectively, adipocyte differentiation via the C/EBPβ-LAP and Smad2 pathway in an autocrine/paracrine manner. Activin A is expressed at higher levels in adipose tissue of obese patients compared with the expression levels in lean subjects. Indeed, activin A levels in adipose progenitors are dramatically increased by factors secreted by macrophages derived from obese adipose tissue. CONCLUSIONS - Altogether, our data show that activin A plays a significant role in human adipogenesis. We propose a model in which macrophages that are located in adipose tissue regulate adipose progenitor self-renewal through activin A.

Original languageEnglish (US)
Pages (from-to)2513-2521
Number of pages9
JournalDiabetes
Volume59
Issue number10
DOIs
StatePublished - Oct 2010

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Adipose Tissue
Adipocytes
Adipogenesis
Macrophages
activin A
White Adipose Tissue
Research Design
Obesity
Fats
Growth

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Zaragosi, L. E., Wdziekonski, B., Villageois, P., Keophiphath, M., Maumus, M., Tchkonia, T., ... Dani, C. (2010). Activin A plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes, 59(10), 2513-2521. https://doi.org/10.2337/db10-0013

Activin A plays a critical role in proliferation and differentiation of human adipose progenitors. / Zaragosi, Laure Emmanuelle; Wdziekonski, Brigitte; Villageois, Phi; Keophiphath, Mayoura; Maumus, Marie; Tchkonia, Tamara; Bourlier, Virginie; Mohsen-Kanson, Tala; Ladoux, Annie; Elabd, Christian; Scheideler, Marcel; Trajanoski, Zlatko; Takashima, Yasuhiro; Amri, Ez Zoubir; Lacasa, Daniele; Sengenes, Coralie; Ailhaud, Gérard; Clément, Karine; Bouloumie, Anne; Kirkland, James L; Dani, Christian.

In: Diabetes, Vol. 59, No. 10, 10.2010, p. 2513-2521.

Research output: Contribution to journalArticle

Zaragosi, LE, Wdziekonski, B, Villageois, P, Keophiphath, M, Maumus, M, Tchkonia, T, Bourlier, V, Mohsen-Kanson, T, Ladoux, A, Elabd, C, Scheideler, M, Trajanoski, Z, Takashima, Y, Amri, EZ, Lacasa, D, Sengenes, C, Ailhaud, G, Clément, K, Bouloumie, A, Kirkland, JL & Dani, C 2010, 'Activin A plays a critical role in proliferation and differentiation of human adipose progenitors', Diabetes, vol. 59, no. 10, pp. 2513-2521. https://doi.org/10.2337/db10-0013
Zaragosi LE, Wdziekonski B, Villageois P, Keophiphath M, Maumus M, Tchkonia T et al. Activin A plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes. 2010 Oct;59(10):2513-2521. https://doi.org/10.2337/db10-0013
Zaragosi, Laure Emmanuelle ; Wdziekonski, Brigitte ; Villageois, Phi ; Keophiphath, Mayoura ; Maumus, Marie ; Tchkonia, Tamara ; Bourlier, Virginie ; Mohsen-Kanson, Tala ; Ladoux, Annie ; Elabd, Christian ; Scheideler, Marcel ; Trajanoski, Zlatko ; Takashima, Yasuhiro ; Amri, Ez Zoubir ; Lacasa, Daniele ; Sengenes, Coralie ; Ailhaud, Gérard ; Clément, Karine ; Bouloumie, Anne ; Kirkland, James L ; Dani, Christian. / Activin A plays a critical role in proliferation and differentiation of human adipose progenitors. In: Diabetes. 2010 ; Vol. 59, No. 10. pp. 2513-2521.
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AU - Zaragosi, Laure Emmanuelle

AU - Wdziekonski, Brigitte

AU - Villageois, Phi

AU - Keophiphath, Mayoura

AU - Maumus, Marie

AU - Tchkonia, Tamara

AU - Bourlier, Virginie

AU - Mohsen-Kanson, Tala

AU - Ladoux, Annie

AU - Elabd, Christian

AU - Scheideler, Marcel

AU - Trajanoski, Zlatko

AU - Takashima, Yasuhiro

AU - Amri, Ez Zoubir

AU - Lacasa, Daniele

AU - Sengenes, Coralie

AU - Ailhaud, Gérard

AU - Clément, Karine

AU - Bouloumie, Anne

AU - Kirkland, James L

AU - Dani, Christian

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N2 - OBJECTIVE - Growth of white adipose tissue takes place in normal development and in obesity. A pool of adipose progenitors is responsible for the formation of new adipocytes and for the potential of this tissue to expand in response to chronic energy overload. However, factors controlling self-renewal of human adipose progenitors are largely unknown. We investigated the expression profile and the role of activin A in this process. RESEARCH DESIGN AND METHODS - Expression of INHBA/activin A was investigated in three types of human adipose progenitors. We then analyzed at the molecular level the function of activin A during human adipogenesis. We finally investigated the status of activin A in adipose tissues of lean and obese subjects and analyzed macrophage-induced regulation of its expression. RESULTS - INHBA/activin A is expressed by adipose progenitors from various fat depots, and its expression dramatically decreases as progenitors differentiate into adipocytes. Activin A regulates the number of undifferentiated progenitors. Sustained activation or inhibition of the activin A pathway impairs or promotes, respectively, adipocyte differentiation via the C/EBPβ-LAP and Smad2 pathway in an autocrine/paracrine manner. Activin A is expressed at higher levels in adipose tissue of obese patients compared with the expression levels in lean subjects. Indeed, activin A levels in adipose progenitors are dramatically increased by factors secreted by macrophages derived from obese adipose tissue. CONCLUSIONS - Altogether, our data show that activin A plays a significant role in human adipogenesis. We propose a model in which macrophages that are located in adipose tissue regulate adipose progenitor self-renewal through activin A.

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