The Effect of Time-restricted Eating on Liver Metabolism (TREL)

Numerous studies have established the role of nutrition on obesity and its related metabolic diseases, which together affect a billion individuals worldwide. Evidence indicate that meal timing regulates numerous metabolic processes suggesting that meal time manipulation may be a simple intervention against obesity and its metabolic diseases. Time-restricted eating (TRE) is a dietary manipulation that involves restricting food intake to 6-10 h/day with no energy intake the rest of the day. In rodents, TRE significantly decreases hepatic steatosis and dyslipidemia, while it supports a healthier hepatic cellular content even without caloric restriction, potentially by alternating activation of nutrient sensing mechanisms and effects on circadian oscillations. However, an understanding of the effect of TRE on liver health in people is not clear. Accordingly, we will conduct a randomized controlled trial in people with overweight/obesity and hepatic steatosis to determine the effect of 9 h TRE for 12 weeks, on key metabolic outcomes in liver health: 1) intrahepatic triglyceride content using magnetic resonance imaging; 2) de novo lipogenesis during fasting and postprandial conditions using administration of deuterated water in conjunction with mathematical modeling. The proposed study will enable us to determine the effect of meal timing on metabolic function in people with NAFLD.

Subjects will consume all meals/snacks during a ~15-h daily eating period (~9-h fasting). The prescribed energy intake will be monitored and adjusted as needed to achieve weight maintenance.

Subjects will consume all meals/snacks during a ~9-h daily eating period (~15-h fasting). The prescribed energy intake will be monitored and adjusted as needed to achieve weight maintenance.

Subjects will consume all meals/snacks during a ~9-h daily eating period (~15-h fasting) without any other dietary advice.

Participants will be asked consume all meals/snacks during a ~9-h daily eating period (~15-h fasting).

DNL will be assessed by using administration of deuterated water and measurement of deuterium enrichment in plasma lipids

Inclusion Criteria: age 25-75 years men and women body mass index 25-45 kg/m2 clinical diagnosis of NAFLD self-reported habitual eating period more than or equal to 14 h per day. Exclusion Criteria: shift worker, recent or expected travel crossing time zones fasting >12-h/day more than once a week *> once a week no food intake after 18:00 habitually waking up before 04:00 and sleeping before 22:30 unstable weight (>5% change in the last 2 months) diabetes mellitus or alcoholic liver disease sleep disorder history of or current eating disorder cancer in last 5 years conditions that render subject unable to complete all testing procedures use of medications that affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued smoking or illegal drug use pregnant or breastfeeding having metals in the body cognitive impairment gastrointestinal or bariatric surgery that affects nutrient digestion and absorption unable to grant voluntary informed consent or comply with the study instructions individuals who are not yet adults (infants, children, teenagers) individuals that are unable to lie motionless on the MRI scanner for an hour or *have tattoos or tattooed eyeliner alcohol abuse prisoners