RESEARCH HIGHLIGHTS Nature Reviews Endocrinology advance online publication 8 July 2014; doi:10.1038/nrendo.2014.107
OBESITY
Adipocyte development—all fat cells are not created equal New findings published in Nature Communications reveal that in mice, white, brown and brite adipocytes have heterogeneous origins, and that these lineages are dynamic and can vary with sex, age and diet. Previously, adipose tissue was considered a single organ. Additionally, brown adipocytes were thought to originate only from progenitor cells that express the transcription factor, myogenic factor 5 (Myf5). In previous work, researchers from the University of Massachusetts Medical School (Worcester, MA, USA) used conditional knockout mice to dissect the signalling pathways that drive differentiation of myocytes and brown adipocytes from mesenchymal progenitor cells that express Myf5. Surprisingly, they discovered that deletion of Pten (which encodes a negative regulator of PI3K signalling) in Myf5-expressing progenitor cells resulted in striking changes in body fat distribution, with both white and brown adipose tissues
Image from Sanchez-Gurmaches, J. & Guertin, D. A. Nat. Commun. doi:10.1038/ncomms5099
being affected. These changes were similar those characteristic of human partial lipodystrophy syndrome. In this study, a lineage-specific dual fluorescent reporter system was used to quantitatively track adipocyte differentiation in vivo. Progenitor cells that expressed both Myf5 and Pax3 gave rise to brown and white adipocytes, however, these cells were not the sole source of brown adipocytes. Several pools of brown adipocytes originated from cells that did not express either of these transcription factors, which supports the hypothesis that these cells have heterogeneous origins.
NATURE REVIEWS | ENDOCRINOLOGY
Sex-specific differences in lineage distributions were also revealed; approximately half of the white adipocytes in the perigonadal white adipose tissue depot of male, but not female, mice were from Pax3-expressing cells. Moreover lineages were dynamic in response to diet and as a function of age. For example, the prevalence of adipocytes from Myf5negative progenitor cells increased in response to short-term exposure to a high-fat diet. “Adipocyte origins could influence body fat distribution patterns and adipocyte metabolic properties,” speculates senior author David Guertin. “This knowledge could help improve the understanding and treatment of comorbidities associated with obesity.” Jennifer Sargent Original article Sanchez-Gurmaches, J. & Guertin, D. A. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat. Commun. doi:10.1038/ncomms5099
ADVANCE ONLINE PUBLICATION © 2014 Macmillan Publishers Limited. All rights reserved
OBESITY
Adipocyte development—all fat cells are not created equal New findings published in Nature Communications reveal that in mice, white, brown and brite adipocytes have heterogeneous origins, and that these lineages are dynamic and can vary with sex, age and diet. Previously, adipose tissue was considered a single organ. Additionally, brown adipocytes were thought to originate only from progenitor cells that express the transcription factor, myogenic factor 5 (Myf5). In previous work, researchers from the University of Massachusetts Medical School (Worcester, MA, USA) used conditional knockout mice to dissect the signalling pathways that drive differentiation of myocytes and brown adipocytes from mesenchymal progenitor cells that express Myf5. Surprisingly, they discovered that deletion of Pten (which encodes a negative regulator of PI3K signalling) in Myf5-expressing progenitor cells resulted in striking changes in body fat distribution, with both white and brown adipose tissues
Image from Sanchez-Gurmaches, J. & Guertin, D. A. Nat. Commun. doi:10.1038/ncomms5099
being affected. These changes were similar those characteristic of human partial lipodystrophy syndrome. In this study, a lineage-specific dual fluorescent reporter system was used to quantitatively track adipocyte differentiation in vivo. Progenitor cells that expressed both Myf5 and Pax3 gave rise to brown and white adipocytes, however, these cells were not the sole source of brown adipocytes. Several pools of brown adipocytes originated from cells that did not express either of these transcription factors, which supports the hypothesis that these cells have heterogeneous origins.
NATURE REVIEWS | ENDOCRINOLOGY
Sex-specific differences in lineage distributions were also revealed; approximately half of the white adipocytes in the perigonadal white adipose tissue depot of male, but not female, mice were from Pax3-expressing cells. Moreover lineages were dynamic in response to diet and as a function of age. For example, the prevalence of adipocytes from Myf5negative progenitor cells increased in response to short-term exposure to a high-fat diet. “Adipocyte origins could influence body fat distribution patterns and adipocyte metabolic properties,” speculates senior author David Guertin. “This knowledge could help improve the understanding and treatment of comorbidities associated with obesity.” Jennifer Sargent Original article Sanchez-Gurmaches, J. & Guertin, D. A. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat. Commun. doi:10.1038/ncomms5099
ADVANCE ONLINE PUBLICATION © 2014 Macmillan Publishers Limited. All rights reserved
