Metabolic health and homeostasis

To what extent can novel dynamic indicators of metabolic processes, such as postprandial metabolic flexibility, improve the prediction of nutrition-related disease risk? What specific definitions of metabolic flexibility and homeostasis are relevant for maintaining metabolic health and preventing metabolic diseases?

Metabolic health remains incompletely understood; this key underlying research gap is a major obstacle to reducing the growing global burden of disease from metabolic diseases and high body mass index. Metabolic flexibility is essential for energy homeostasis and maintenance of metabolic health. Broadly, metabolic flexibility is defined as the body’s ability to appropriately respond to physiologic challenges allows for homeostatic regulation during meals, exercise, and rest. With Dr. Aryeh Stein (Emory University), we evaluated postprandial metabolic flexibility through comparing high-resolution non-targeted metabolomic profiles at two hours after consuming a standardized meal challenge, relative to while fasting [1, 2, 3]. Energy, macronutrient, and bile acid metabolism pathways were responsive to the meal challenge among healthy individuals [1]. Compared to the postprandial response between  adults with versus without cardiometabolic diseases (hypertension, diabetes, metabolic syndrome, or obesity), those with cardiometabolic diseases showed a greater number of metabolomic features that were altered [2]. Assuming that most observed metabolites are homeostatically regulated, this finding suggested lower metabolic flexibility among those with CMDs [2]. Postprandial metabolomic profile response to a standardized meal challenge also differed based on fasting inflammation status [4]. 

Selected Publications
1.    Yu EA, Yu T, Jones DP, Martorell R, Ramirez-Zea M, Stein AD. Macronutrient, Energy, and Bile Acid Metabolism Pathways Altered Following a Physiological Meal Challenge, Relative to Fasting, among Guatemalan Adults. J Nutr, 2020. 150(8): 2031-2040.
2.    Yu EA, Yu T, Jones DP, Ramirez-Zea M, Stein AD. Metabolomic profiling after meal shows greater changes and lower metabolic flexibility in cardiometabolic diseases. J Endocr Soc, 2020.
3. Yu EA, Le NA, Stein AD. Measuring postprandial metabolic flexibility to assess metabolic health and disease. J Nutr, 2021. DOI: 10.1093/jn/nxab263. In press.
4. Yu EA, He S, Jones DP, Sun YV, Ramirez-Zea M, Stein AD. Metabolomic profiling demonstrates postprandial changes in fatty acids and glycerophospholipids are associated with fasting inflammation in Guatemalan adults. J Nutr, 2021. DOI: 10.1093/jn/nxab183. In press.