TY  - JOUR
A1  - Gohlke, Sabrina
A1  - Zagoriy, Vyacheslav
A1  - Inostroza, Alvaro Cuadros
A1  - Meret, Michael
A1  - Mancini, Carola
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Kuhlow, Doreen
A1  - Graja, Antonia
A1  - Stephanowitz, Heike
A1  - Jähnert, Markus
A1  - Krause, Eberhard
A1  - Wernitz, Andreas
A1  - Petzke, Klaus-Juergen
A1  - Schürmann, Annette
A1  - Kleuser, Burkhard
A1  - Schulz, Tim Julius
T1  - Identification of functional lipid metabolism biomarkers of brown adipose tissue aging
JF  - Molecular Metabolism
N2  - 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.
KW  - Brown adipose tissue
KW  - Aging
KW  - Ceramides
KW  - Sphingolipids
KW  - Dolichol lipids
Y1  - 2019
U6  - https://doi.org/10.1016/j.molmet.2019.03.011
SN  - 2212-8778
VL  - 24
SP  - 1
EP  - 17
PB  - Elsevier
CY  - Amsterdam
ER  -