A Western diet pattern, characterized by a low intake of fruits and vegetables and a high intake of sugar and processed foods, promotes the development of obesity and metabolic disease. Time restricted eating has been shown to decrease weight and improve metabolic health in humans. However, factors such as age and sex modulate both susceptibilty to obesity and likelihood of responding to weight-loss treatments. Authors of a new report found that male mice experienced greater metabolic benefit from time-restricted feeding than females.
Time-restricted eating, the practice of limiting food intake to an 8- or 12-hour window, is an emerging therapy for the treatment and prevention of metabolic diseases. Much of the research about time-restricted eating in humans is based on research of time-restricted feeding in mice, which has elucidated many of the cellular mechanisms related to [time-restricted eating’s benefits.](https://journals.physiology.org/doi/full/10.1152/ajpregu.00775.2005) These two terms distinguish which population, humans or non-human animals, is practicing time-restricted food intake.
The prevalence of obesity is on the rise in the industrialized world, a problem compounded by an increasing average age in the same populations. The accumulation of extra fat throughout life puts a person at greater risk of metabolic disease as they age. Females are more likely to gain and retain fat mass than males; however, pre-menopausal females tend to have lower rates of type 2 diabetes and cardiovascular disease due to the protective effects of estrogen. Previous research in humans has demonstrated weight loss and improved metabolic health with time-restricted eating; however, additional research is needed to understand the sex- and age-dependent effects of time-restricted eating.
The researchers used male and female mice of two ages: three months old (equivalent to 20-year-old humans) and 12 months old (equivalent to 42 year-old-humans). They fed mice a chow diet representative of a Western diet pattern with 17 percent of calories from sugar (human equivalent of about 25 ounces of soda per day) and 45 percent of calories from fat including lard and soybean oil. Current dietary guidelines recommend limiting solid fats such as lard). Half of the mice had 24-hour access to food while the other half only had restricted access, limited to just nine hours per day. Mice continued their diet for a total of 12 to 13 weeks. After 10 weeks, the researchers measured changes in the animals' body weight, glucose sensitivity, serum cholesterol, fatty liver, muscle performance, and immune response when challenged with bacterial endotoxin.
Although mice in the time-restricted feeding group consumed the same amount of food as mice with constant access to food, time-restricted feeding resulted in 15 percent less weight gain in young male mice and 23 percent less weight gain in older male mice. Time-restricted feeding did not significantly prevent weight gain in female mice. Male mice also experienced a greater reduction in serum cholesterol with time-restricted feeding compared to females. Both older male and female mice had lower rates of insulin resistance and fatty liver while on time-restricted feeding. This protection was likely due to changes in gene expression that increased glucose uptake by and decreased glucose output from the liver. In young male mice, time-restricted feeding preserved muscle mass, function, and performance, but not in young females. Finally, when challenged with bacterial endotoxin, older mice practicing time-restricted feeding were significantly more likely to survive septic shock than mice with 24-hour access to food, demonstrating better health and resilience.
Time-restricted feeding improved survival of septic shock and provided protection against insulin resistance and fatty liver in both sexes; however, male mice experienced greater reductions in body weight and serum cholesterol and maintained greater muscle mass and performance compared to female mice. The authors noted that their research is of particular interest considering the increased risk of severe COVID-19 illness in those with poor metabolic health.
