Circadian Rhythms and Fat Metabolism

The increase in obesity rates is posing serious consequences on public health as the increasing need for liver transplantation is unable to supply the demand. It is well understood that obesity results in the accumulation of fat in the liver which can cause an array of health problems such as inflammation, hepatitis and liver failure. This potential increase in the need for liver transplantation calls for an urgent focus on treatment.

Dr. Mitchell Lazar from the University of Pennsylvania’s School of Medicine investigated how drug therapy could be made more effective by looking at specific protein targets. Interestingly, they found that diet-induced obesity (DIO) causes changes in the gene transcription of a protein called, PPAR-alpha, a protein important for the regulation of fatty acid oxidation. Furthermore, DIO was shown to cause changes in the circadian rhythm of the liver thereby causing fatty acid oxidation and synthesis to become synchronous (Guan, 2018). When comparing times of day and fatty oxidation activity, the researchers actually found that the body’s fat burning activity, more specifically, the activity of PPAR-alpha protein activity, peaked around 5 p.m.. Now, in the interest of maximizing the efficacy of lipid-reducing drugs such as fibrates, these drugs were deemed to be most effective when administered at 5 p.m when the activity of PPAR-alpha is at its peak activity as well (Guan et al., 2018). The chronotherapeutic activity of this drug further suggests that the body’s circadian rhythm plays an important role in metabolism even in healthy individuals. This link of metabolism to circadian rhythm raises concerns for individuals who’s circadian rhythms are disrupted such as if you work the night shift or in individuals with sleep disorders. If fat breakdown is affected by one’s circadian rhythm, then this begs the question: does working the night shift increase your likelihood of developing a metabolic disorder?

Guan, D., Xiong, Y., Borck, P. C., Jang, C., Doulias, P., Papazyan, R., . . . Lazar, M. A. (2018). Diet-Induced Circadian Enhancer Remodeling Synchronizes Opposing Hepatic Lipid Metabolic Processes. Cell,174(4). doi:10.1016/j.cell.2018.06.031

University of Pennsylvania School of Medicine. (2018, July 26). Fat production and burning are synchronized in livers of mice with obesity. ScienceDaily. Retrieved December 5, 2018 from www.sciencedaily.com/releases/2018/07/180726162757.htm