Metabolites are substances produced by a metabolic process, such as glucose generated in the metabolism of complex sugars and starches, or amino acids used in the biosynthesis of proteins. How do mammals keep two biologically crucial metabolites in balance during times when they are feeding, sleeping, and fasting? New research provides some insight that might also be useful in dealing with a disease such as obesity.
Findings from UT Southwestern Medical Center point to an interesting relationship between body fat and your liver. Fat cells help your liver to regulate both glucose (energy) and uridine, a metabolite that plays a role in a wide range of processes, including storing glucose reserves, building RNA molecules, and producing proteins. Glucose is used for energy, but uridine is vital for cellular function, growth, and repair. It’s essentially a building block for your body.
The liver is the main producer of uridine, but it turns out only when you are in a fed state. In dietary studies, the researchers found that prolonged exposure to a high-fat diet blunted the effects of fasting on lowering body temperature, an effect also associated with obesity. This study shows when you are in a fasting state, your body’s fat cells take over uridine production. This leads to increased activity in the fat cells, which could lead to a faster burning metabolic state.
A regulatory model of energy homeostasis during fasting/refeeding. The liver is the predominant biosynthetic organ and contributor to plasma uridine in the fed state, whereas the adipocyte dominates uridine biosynthetic activity in the fasted state. Biliary excretion is the primary mechanism for plasma uridine clearance. Because nutrient intake triggers bile release, plasma uridine levels are elevated during fasting and drop rapidly in the postprandial state. The fasting-associated increase of plasma uridine elicits a hypothalamic response culminating in body temperature lowering, whereas bile-mediated uridine release promotes a decline of plasma uridine and enhances insulin sensitivity. (Click to enlarge)
The real benefit of this study was a clearer understanding of the role fat cells play in the production of uridine. Knowing the fat takes over uridine production during fasting indicates that the body is always working toward more efficient glucose metabolism and cellular function. The findings of this research could impact the way we deal with diseases such as diabetes, as well as obesity.
1. Yingfeng Deng, Zhao V. Wang, Ruth Gordillo, Yu An, Chen Zhang, Qiren Liang, Jun Yoshino, Kelly M. Cautivo, Jef De Brabander, Joel K. Elmquist, Jay D. Horton, Joseph A. Hill, Samuel Klein, Philipp E. Scherer. “An adipo-biliary-uridine axis that regulates energy homeostasis.” Science, 2017; 355 (6330): eaaf5375.