@article{GrajaGarciaCarrizoJanketal.2018,
  author    = {Graja, Antonia and Garcia-Carrizo, Francisco and Jank, Anne-Marie and Gohlke, Sabrina and Ambrosi, Thomas H. and Jonas, Wenke and Ussar, Siegfried and Kern, Matthias and Sch{\"u}rmann, Annette and Aleksandrova, Krasimira and Bluher, Matthias and Schulz, Tim Julius},
  title     = {Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism},
  series = {Aging Cell},
  volume    = {17},
  journal   = {Aging Cell},
  number    = {5},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1474-9718},
  doi       = {10.1111/acel.12810},
  pages     = {13},
  year      = {2018},
  abstract  = {Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue-resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high-fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age-related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age-related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.},
  language  = {en}
}
@phdthesis{Graja2017,
  author    = {Graja, Antonia},
  title     = {Aging-related changes of progenitor cell function and microenvironment impair brown adipose tissue regeneration},
  school      = {Universit{\"a}t Potsdam},
  pages     = {152},
  year      = {2017},
  language  = {en}
}
@article{GohlkeZagoriyInostrozaetal.2019,
  author    = {Gohlke, Sabrina and Zagoriy, Vyacheslav and Inostroza, Alvaro Cuadros and Meret, Michael and Mancini, Carola and Japtok, Lukasz and Schumacher, Fabian and Kuhlow, Doreen and Graja, Antonia and Stephanowitz, Heike and J{\"a}hnert, Markus and Krause, Eberhard and Wernitz, Andreas and Petzke, Klaus-Juergen and Sch{\"u}rmann, Annette and Kleuser, Burkhard and Schulz, Tim Julius},
  title     = {Identification of functional lipid metabolism biomarkers of brown adipose tissue aging},
  series = {Molecular Metabolism},
  volume    = {24},
  journal   = {Molecular Metabolism},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {2212-8778},
  doi       = {10.1016/j.molmet.2019.03.011},
  pages     = {1 -- 17},
  year      = {2019},
  abstract  = {Objective: Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism. Methods: Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined. Results: Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation. Conclusions: Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.},
  language  = {en}
}