Characterization of immortalized human brown and white pre-adipocyte cell models from a single donor.
Lasse K. Markussen,Marie S. Isidor,Peter Breining,Peter Breining,Elise S. Andersen,Nanna E. Rasmussen,Louise I. Petersen,Steen B. Pedersen,Steen B. Pedersen,Bjørn Richelsen,Bjørn Richelsen,Jacob B. Hansen +11 more
TLDR
The authors used retrovirus-mediated overexpression to stably integrate human telomerase reverse transcriptase (TERT) into stromal-vascular cell fractions from deep and superficial human neck adipose tissue biopsies from the same donor.Abstract:
Brown adipose tissue with its constituent brown adipocytes is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. The molecular control of brown adipocyte differentiation and function has been extensively studied in mice, but relatively little is known about such regulatory mechanisms in humans, which in part is due to lack of human brown adipose tissue derived cell models. Here, we used retrovirus-mediated overexpression to stably integrate human telomerase reverse transcriptase (TERT) into stromal-vascular cell fractions from deep and superficial human neck adipose tissue biopsies from the same donor. The brown and white pre-adipocyte cell models (TERT-hBA and TERT-hWA, respectively) displayed a stable proliferation rate and differentiation until at least passage 20. Mature TERT-hBA adipocytes expressed higher levels of thermogenic marker genes and displayed a higher maximal respiratory capacity than mature TERT-hWA adipocytes. TERT-hBA adipocytes were UCP1-positive and responded to β-adrenergic stimulation by activating the PKA-MKK3/6-p38 MAPK signaling module and increasing thermogenic gene expression and oxygen consumption. Mature TERT-hWA adipocytes underwent efficient rosiglitazone-induced 'browning', as demonstrated by strongly increased expression of UCP1 and other brown adipocyte-enriched genes. In summary, the TERT-hBA and TERT-hWA cell models represent useful tools to obtain a better understanding of the molecular control of human brown and white adipocyte differentiation and function as well as of browning of human white adipocytes.read more
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Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism.
Mette Ji Riis-Vestergaard,Mette Ji Riis-Vestergaard,Mette Ji Riis-Vestergaard,Bjørn Richelsen,Bjørn Richelsen,Bjørn Richelsen,Jens M. Bruun,Jens M. Bruun,Wei Li,Jacob B. Hansen,Steen B. Pedersen,Steen B. Pedersen,Steen B. Pedersen +12 more
TL;DR: UCP1 expression in human BAT may, unlike in rodents, primarily be regulated by ADRB1, and these findings may have implications for ADRB agonists as future therapeutic compounds for human BAT activation.
Journal ArticleDOI
Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis.
Olivia Sveidahl Johansen,Olivia Sveidahl Johansen,Tao Ma,Jakob Bondo Hansen,Lasse K. Markussen,Renate Schreiber,Laia Reverte-Salisa,Hua Dong,Dan Ploug Christensen,Wenfei Sun,Thorsten Gnad,Iuliia Karavaeva,Thomas Nielsen,Sander Kooijman,Cheryl Cero,Oksana Dmytriyeva,Yachen Shen,Maria Razzoli,Shannon L. O'Brien,Shannon L. O'Brien,Shannon L. O'Brien,Eline N. Kuipers,Carsten H. Nielsen,William Orchard,Nienke Willemsen,Naja Z. Jespersen,Morten Lundh,Elahu G. Sustarsic,Cecilie Mørch Hallgren,Mikkel Frost,Seth McGonigle,Marie S. Isidor,Christa Broholm,Oluf Pedersen,Jacob B. Hansen,Niels Grarup,Torben Hansen,Andreas Kjaer,James G. Granneman,M. Madan Babu,M. Madan Babu,Davide Calebiro,Davide Calebiro,Davide Calebiro,Søren Nielsen,Mikael Rydén,Raymond E. Soccio,Patrick C.N. Rensen,Jonas T. Treebak,Thue Walter Schwartz,Brice Emanuelli,Alessandro Bartolomucci,Alexander Pfeifer,Rudolf Zechner,Camilla Scheele,Susanne Mandrup,Zachary Gerhart-Hines,Zachary Gerhart-Hines +57 more
TL;DR: In this paper, the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand.
Journal ArticleDOI
In vitro and ex vivo models of adipocytes.
Jérémy Dufau,Jérémy Dufau,Joanne X. Shen,Morgane Couchet,Thais de Castro Barbosa,Niklas Mejhert,Lucas Massier,Elena Griseti,Elena Griseti,Etienne Mouisel,Etienne Mouisel,Ez-Zoubir Amri,Volker M. Lauschke,Mikael Rydén,Dominique Langin,Dominique Langin,Dominique Langin +16 more
TL;DR: In this article, the authors survey various models of differentiated preadipocyte cells and primary mature adipocyte survival describing main characteristics, culture conditions, advantages, and limitations of these models.
Journal ArticleDOI
Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro
Peter Breining,Jonas Jensen,Elias Immanuel Ordell Sundelin,Lars C. Gormsen,Steen Jakobsen,Morten Busk,Lars Rolighed,Peter Bross,Paula Fernandez-Guerra,Lasse K. Markussen,Lasse K. Markussen,Nanna E. Rasmussen,Jacob B. Hansen,Steen B. Pedersen,Bjørn Richelsen,Niels Jessen,Niels Jessen +16 more
TL;DR: To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11C]‐metformin tracer in mice and studying in vitro effects of met formin on cultured human brown adipocytes.
Journal ArticleDOI
The colorful versatility of adipocytes: white-to-brown transdifferentiation and its therapeutic potential in humans.
TL;DR: It is estimated that converting a small percentage of existing white fat mass in obese subjects into active brite adipocytes could be sufficient to achieve meaningful benefits in metabolism, and novel browning agents have to be identified before adipocyte transdifferentiation can be realized as a safe and efficacious therapy.
References
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