CIRCADIAN REGULATION OF OXIDATIVE FAT METABOLISM IN C2C12 MYOTUBES

Author

David Bacsik

Date of Award

2014

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Clore, Amy

Keywords

Circadian Rythms, Metabolism, C2C12, Biology

Area of Concentration

Biology

Abstract

The molecular circadian clock consists of a transcription-translation feedback loop that drives the rhythmic expression of hundreds of genes. The rate-limiting enzyme of the NAD+ salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), is a known target of the molecular circadian clock. Recently, the Bass Lab group at Northwestern University elucidated an NAD+ dependent pathway connecting the molecular circadian clock to fatty acid oxidation in mouse liver. Circadian regulation of oxidative fat metabolism coordinates metabolic activities with circadian feeding and fasting behaviors. To facilitate further study of this pathway, a mouse skeletal muscle cell line, C2C12, was tested as a model system for studying fat metabolism and circadian clock function. Rhythms of NAD+ concentration and mitochondrial respiration were observed in synchronized C2C12 myotubes. NAMPT was found to have substantial influence on cellular NAD+ concentrations, however, NAMPT expression as measured by qPCR varied little throughout the day. These data suggest that, although further investigation into the regulation of NAMPT activity is required, the C2C12 cell line may be a useful model for the study of circadian metabolism.

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