Project Abstract In the United States, about 34% of adults meet criteria for metabolic syndrome, which is characterized by the presence of multiple risk factors for cardiovascular disease and diabetes. Diet and lifestyle interventions are critical to prevent disease progression in patients with type II-diabetes mellitus and cardiometabolic disease. However, patient adherence is low with existing interventions that focus on changing the quality and quantity of nutrition and activity. Thus, a new method of prevention and treatment is greatly needed. Recent studies have shown that the timing of eating also plays a large role in metabolism. Circadian rhythms optimize nutrient homeostasis by orchestrating daily rhythms in catabolic and anabolic metabolism to appropriate time during the 24-hour day. Chronic circadian rhythm disruption due to lifestyle including erratic eating patterns predisposes individuals to metabolic diseases including type 2 diabetes and obesity. In rodents, 8-12 h of time-restricted feeding without altering calorie consumption or food composition can prevent and reverse diet-induced obesity and its associated metabolic dysfunction. Consequently, the diurnal regulation of metabolism through alternating periods of feeding and fasting offers a promising avenue for the prevention and treatment of metabolic disease. The major objective of this proposal is to determine the efficacy of restricting daily calorie intake to a reduced/fixed number of hours per day (time-restricted feeding, TRF) to improve metabolic health. We will achieve this with the following specific aims: 1) Evaluate the impact of TRF on glucose homeostasis with exploratory aims to assess changes in mitochondrial structure and gene expression in skeletal muscle and 2) Assess the changes in metabolic biomarkers in response to TRF. 3) Assess the impact of TRF on body composition. In this study, we will ask participants who have been diagnosed with metabolic syndrome to restrict their food intake to 10 hours a day and fast for 14 hours for 12-weeks. Eating, sleeping, and activity patterns will be assessed throughout the study with a smartphone app. Sleeping and activity patterns will also be observed with actiwatches for one week at baseline and one week at the end of the study. Glucose homeostasis, metabolic biomarkers, and body composition will be assessed at baseline and at the end of the TRF intervention. In addition, we will conduct skeletal muscle biopsies to assess the changes in mitochondrial structure by light microscopy and in critical proteins that regulate mitochondrial function. We hypothesize that imposing feeding- fasting cycles (TRF) will restore the equilibrium between catabolic and anabolic processes, which will improve glucose homeostasis and cardiometabolic biomarkers, decrease abdominal fat, and enhance mitochondrial function.