Analysis of the effects of age-related changes in the microenvironment on brown adipocyte formation and function

Einleitung:

Brown adipose tissue (BAT) drives non-shivering thermogenesis, thereby allowing mammals to maintain a constant body core temperature in a cold environment. The thermogenic capacity of this tissue is due to its high content of mitochondria and the expression of Uncoupling protein 1 (Ucp1). BAT is actively involved in metabolic control and it is well established that during aging there is a loss of classical brown adipocytes as well as reduced browning capacity of white adipose tissue. The reduction of BAT energy-expenditure might contribute to an obesity-prone phenotype with increased age, thereby contributing to the progression of metabolic disorders.

Methoden:

By the integration of transcriptomic and proteomic data analyses of BAT from young and old C57BL/6 mice, a group of candidate genes was generated with display age-related expression changes. To further test their functional relevance, brown adipocyte cell lines are used to generate in vitro gain-/loss-of-function models.

Ergebnisse:

Novel candidate genes belonging to different physiological processes, such as lipid metabolism pathways, have been identified, that may play an active role during the age-associated metabolic dysfunction of BAT.

Schlussfolgerung:

The profiling of the candidate genes allows us to characterize the molecular events leading to a decline in thermogenic potential during BAT-aging.