Brown adipose NADH oxidase for thermogenesis

NIH RePORTER · NIH · R01 · $454,471 · view on reporter.nih.gov ↗

Abstract

Obesity has become a global epidemic and is associated with type 2 diabetes and other chronic diseases. While WAT is the primary energy storage organ, brown adipose tissue (BAT) dissipates energy through non-shivering thermogenesis to maintain body temperature. Recently, a new brown fat specific cold inducible protein that has a NADH oxidase domain has been identified in the lab. While this NADH oxidase is lipid droplet associated, it localizes at the mitochondria during thermogenesis. The hypothesis of this research is that, through NADH oxidation, this enzyme uniquely functions in brown fat to regenerate NAD from NADH for optimal glycolysis in cytosol, while transferring electrons to mitochondrial electron transport chain, during thermogenesis. Initial examinations of NADH oxidase knockout mice that recently have generated show impaired thermogenesis with increased adiposity. In addition, transgenic mice overexpressing this NADH oxidase protein in brown adipocytes have been generated that showed enhanced thermogenesis. With these loss- and gain-of function mouse models in hand, the role and the underlying mechanism for this NADH oxidase in cold induced thermogenesis will be investigated.

Key facts

NIH application ID
9993936
Project number
1R01DK123843-01A1
Recipient
UNIVERSITY OF CALIFORNIA BERKELEY
Principal Investigator
Hei Sook Sul
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$454,471
Award type
1
Project period
2020-04-09 → 2024-02-29