Time Restricted Feeding and Metabolic Rhythms

Current guidelines for the prevention and treatment of obesity focus on caloric restriction diets and increasing physical activity, but long-term compliance to these strategies is poor. The timing of meal intake relative to the light-dark and sleep-wake cycle is rarely considered in metabolic health; and modifying meal timing is likely easier to implement in daily life than reducing caloric intake and/or increasing physical activity. This project will test whether restricting the timing of energy intake to a short-defined period during wakefulness can be used to improve fuel utilization patterns and enhance circadian rhythms in metabolic tissues to optimize health.

Time restricted feeding (TRF; eating within \<10-h period followed by \>14-h fast) is a promising meal timing paradigm that in rodent studies improves multiple health indicators. When provided access to a high-fat diet ad libitum, mice rapidly gain weight. However, when fed the same diet under TRF conditions (food access restricted to an 8-h window during the active phase) mice appear to be protected from excessive weight gain and metabolic diseases. Preliminary studies in humans are showing improvements in 24-h glucose variability, fat oxidation, and blood pressure with TRF aligned to the early portion of the day compared to the ad libitum feeding schedule. A major research gap is whether the timing of the feeding window relative to sleep modifies metabolic responses. In a recent pilot and feasibility study incorporating TRF into a weight loss intervention the researchers asked participants to consume all food within a 10-h window to starting 1-h after waking for 12-weeks. The researchers' design choice was based on data showing that consuming energy in the evening is related to a two-fold increase in obesity risk. There also appears to be reduced weight loss effectiveness in dieters who consume the main meal later in the day. Some of the participants in the weight loss trial reported difficulty adhering to the early feeding schedule because it does not align well with social schedule (e.g., eating dinner with the family in the evening). Therefore, an important clinical question is whether late or mid-day TRF will result in similar metabolic benefits compared to the early TRF paradigm that has been tested in other studies.

Additional rationale for studying early vs. late timed feeding is to address a fundamental question, "can timed meals shift the timing of metabolic rhythms?". Peripheral circadian clocks located in liver, adipose, and muscle tissue are sensitive to meal timing and control daily oscillations in fuel utilization and storage. A small study of 8 men demonstrated that a 5-h delay and meal timing was sufficient to delay the rhythmic expression of clock genes in white adipose tissue. Therefore, the investigators will leverage the design of the present study to examine the impact of meal timing on peripheral circadian rhythms in metabolism and their alignment to the sleep cycle.

Eligibility Criteria:
Inclusion Criteria:

* Men and women with overweight and class I obesity (N=12, Age=20-50 years; BMI 25-35 kg/m2)
* Low physical activity level (≤150 min/wk of moderate-to-vigorous activity);
* For Females- Not currently pregnant or lactating and not pregnant within the past 6 months
* Habitually consume food over a window of \>12 h/day;
* Pass a medical and physical screening performed by the study physician.
* Report a habitual, regular sleep-wake cycle for the month preceding screening that involved going to bed between 2200 and 0100h and getting up between 0600 and 0900 h with \>7 h and \<9.25 h in bed;
* Agree to eat control diets at imposed times for 1 week prior to the inpatient CTRC visits;
* Agree to keep a regular sleep/wake schedule for the duration of the study
* Possess a smart phone to install and utilize the meal timing application.

Exclusion Criteria:

* Subjects must not be currently participating in another research study that would influence their safe participation in this study. For example, subjects must not be participating in a research study in which they ingest experimental medication, or which involves blood samples, since both of these factors could increase risk of participation;
* Being considered unsafe to participate as determined by the study physician;
* Taking medications affecting weight, triglycerides, energy intake/energy expenditure, or sleep in the last 3 months;
* Having abnormal blood chemistry and/or hematology as deemed significant by the study physician;

  o Have one or more of the following out-of-range values measured on a fasting blood sample: glucose \> 126 mg/dl, HbA1c \> 6.5%, thyroid stimulating hormone \<0.5 or \>5.0 uU/ml. Subjects who may be anemic (hemoglobin \<14.5 g/dl men, \<12.3 g/dl women), have abnormal liver function tests (alanine amino transferase \> 47 U/l, aspartate aminotransferase, \> 47 U/l, alkaline phosphatase \<39 or \>117 U/l) or creatinine (\>1.1 mg/dl)
* Significant abnormality in clinical laboratory values
* Ever having a history of systemic, psychiatric, neurological disease, or drug and alcohol abuse;
* History of cardiovascular disease, diabetes, uncontrolled hypertension, untreated thyroid, renal, hepatic diseases, dyslipidemia or any other medical condition affecting weight or lipid metabolism;
* Score \> 18 on Beck Depression Index (BDI) will require further assessment by the study physician to determine if it is appropriate for the subject to participate in the study;
* Use of a continuous positive airway pressure (CPAP) device for the treatment of obstructive sleep apnea (OSA). A score of \>10 on the Epworth sleepiness scale or \>5 on the Pittsburgh Sleep Quality Index will require further assessment by the study physician to determine if it is appropriate for the subject to participate in the study;
* Being positive for human immunodeficiency virus or hepatitis B or C;
* Being a smoker or having been a smoker in the previous 6 months;
* Abnormal eating patterns identified by registered dietician interview (dietary fat\<15%, dietary fat\>45%, dietary protein \>30%);
* Working night shifts;
* Night eating syndrome (at least 25% of food intake is consumed after the evening meal and/or at least two episodes of nocturnal eating per week);
* Traveling \> 2 time zones 2 weeks prior to an inpatient CTRC study visit;
* Currently participating in any formal weight loss or physical activity programs or clinical trials.
* Having a clinically significant allergy (e.g., to food stuffs such as shellfish, peanuts);
* Celiac disease or known sensitivity to gluten (the metabolic kitchen is not gluten free certified and cannot accommodate this dietary restriction)