Time-restricted feeding to mitigate metabolic impairments during circadian misalignment

PROJECT SUMMARY/ABSTRACT
People who work evening, night or rotating shifts (i.e. “nonstandard” work hours) represent one in five
U.S. employees and are alarmingly 44% more likely to develop Type 2 diabetes (T2D) compared to people
who work standard day shifts. Circadian misalignment is one mechanism suggested to increases the risk of
obesity and diabetes in people who work non-standard hours, and is highly prevalent and often unavoidable in
modern, 24-hour society (e.g. shift work, long work hours, jet lag, medical residency, emergency responders,
military personnel, Daylight Savings Time changes, etc). Disruptions in sleep and circadian rhythms have been
linked to insulin resistance, increased energy intake, weight gain, and increased total body, abdominal and
intrahepatic fat content, yet there have been limited attempts at identifying strategies or countermeasures to
prevent the impact of such disruption on T2D risk in a sizeable proportion of the population.
Therefore, our long-term goal is to identify and develop effective, behavioral countermeasures to
combat the increased risk for metabolic diseases associated with sleep and circadian disruption when these
behaviors are unavoidable. The overall objective for this project is to test the impact of time-restricted feeding
to a 7h period in the day as a noninvasive countermeasure to the metabolic impairments associated with
circadian misalignment. Our central hypothesis is that time-restricted feeding to the daytime period will prevent
metabolic impairments during circadian misalignment compared to a condition where energy is consumed
throughout the day and night. The rationale for the proposed project is that defining a non-invasive, scalable
and feasible countermeasure to circadian misalignment could mitigate the risk of obesity and T2D.
To test our overall hypothesis, will use a randomized crossover study with a rigorous inpatient diet-,
activity and light-controlled protocol in 32 healthy men and women. We will determine the impact of time-
restricted feeding during circadian misalignment on 1) muscle tissue insulin sensitivity and gene expression;
and 2) muscle tissue lipid accumulation and circulating nocturnal FFA and glucose concentrations.
Findings from this study represent a critical advancement in the fields of translational circadian and
metabolic physiology by identifying and testing a countermeasure to circadian misalignment. Achievement of
our proposed aims could lead to the development of new intervention strategies for chronic disease prevention
and management. The knowledge to be gained offers the potential to support cost-effective programs that may
inform our healthcare approach to metabolic disease prevention in populations at risk for these diseases such
as shift workers, individuals with sleep disorders and anyone who eats outside of daytime hours.

Grant Number: 5R01DK125653-05
NIH Institute/Center: NIH
Principal Investigator: Josiane Broussard