Non-Coding RNAs and Brown Adipose Tissue (BAT)

• Applicant: Dr. Jan-Wilhelm Kornfeld
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2013 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 239235507

Obesity and type 2 diabetes mellitus constitute two tightly linked, steadily increasing health concerns, for which to date only limited therapeutical strategies exist. Through the recent identification of functional brown adipose tissue (BAT) in adult humans and the unique property of BAT cells to dissipate chemical energy from ingested nutrients in the form of heat, BAT has been identified as a novel target for anti-obesity intervention (1). Thus, identifying novel regulatory pathways that control BAT differentiation, activation and function is of critical, timely importance. In previous work we have unraveled a critical role for miRNA-mediated posttranscriptional gene silencing in the development of obesity-associated hepatic insulin resistance (2). In the current proposal I present an ambitious research plan aimed at unraveling the role of Non-Coding RNAs during differentiation and homeostasis of brown fat cells. This approach will involve a broad range of experimental in vitro and in vivo techniques aiming at i. identifying critical miRNAs and other Non-Coding RNAs implicated in the control of BAT-differentiation and the concomitant deterioration of BAT function in obesity via whole-miRNome and Affymetrix gene expression profiling,ii. Defining their role in the control of BAT differentiation, regulation of mitochondrial activity and whole-body metabolism via loss- and gain-of-function approaches both in cultured brown adipocytes and in transgenic mouse models, andiii. Ultimately identifying the underlying target pathways of relevant miRNA and other Non-Coding RNAs through combined computational and proteomic techniques. Collectively, this experimental strategy will allow to gain novel insights into key regulatory mechanisms of BAT differentiation and function, which ultimately may reveal promising new targets for anti-obesity intervention.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Bioenergetics analyzer
• Instrumentation Group: 3560 Warburg-Apparaturen, Zellstoffwechsel-Analysengeräte