Time-restricted eating could prevent obesity-related muscle dysfunction

“This study elucidates potential mechanisms behind time-restricted feeding’s protective properties against skeletal muscle dysfunction and metabolic impairment induced by obesity,” said Girish Melkani, one of the study authors and a professor at UAB, in an institutional press release.

Obesity and muscle dysfunction

A common misconception is that overweight people have strong muscles and bones. However, there is only a limit to which muscles and bones can get strong in a person with respect to his or her body mass. Beyond that limit, any extra mass causes the weakening of skeletal muscles.

This is why many individuals living with obesity face reduced mobility, difficulty changing their body posture, recurring body pain, and a high risk of musculoskeletal disorders such as arthritis. 

Some past studies have also highlighted that TRF could help people lose weight and protect against the deterioration of skeletal muscles, but this study goes one step further and reveals the internal genetic mechanism driving these benefits.

The fruit-fly experiment

The study authors observed two groups of obese fruit flies; members of the first group were free to consume a fat-rich diet for 24 hours a day, but the flies in the second group could eat the same food for only 12 hours a day. 

The researchers then checked the metabolism, muscular strength, and gene expression in fruit flies at times when they were flying. They found that members of the second group experienced reduced insulin resistance, decreased intramuscular fat, and improved muscle quality as a result of TRF.

They also noticed low levels of fat-processing enzymes that increase the risk of a heart attack in humans. Plus, there was an increase in the activity of genes associated with the production of glycine, an amino acid that benefits the metabolism of the human body.

Although the approach hasn’t been tested on humans yet, the findings of the current study suggest that TRF could emerge as an effective means of treating the various ill effects of obesity in overweight individuals.

“Our mechanistic approach — along with interventions including time-restricted eating — will be highly useful in addressing and treating the obesity, cardiovascular disease, and dementia disparities seen in the Deep South,” said Professor Melkani.

The study is published in the journal Nature Communications.

Study Abstract: 

Obesity caused by genetic and environmental factors can lead to compromised skeletal muscle function. Time-restricted feeding (TRF) has been shown to prevent muscle function decline from obesogenic challenges; however, its mechanism remains unclear. Here we demonstrate that TRF upregulates genes involved in glycine production (Sardh and CG5955) and utilization (Gnmt), while Dgat2, involved in triglyceride synthesis, is downregulated in Drosophila models of diet- and genetic-induced obesity. Muscle-specific knockdown of Gnmt, Sardh, and CG5955 leads to muscle dysfunction, ectopic lipid accumulation, and loss of TRF-mediated benefits, while knockdown of Dgat2 retains muscle function during aging and reduces ectopic lipid accumulation. Further analyses demonstrate that TRF upregulates the purine cycle in a diet-induced obesity model and AMPK signaling-associated pathways in a genetic-induced obesity model. Overall, our data suggest that TRF improves muscle function through modulations of common and distinct pathways under different obesogenic challenges and provides potential targets for obesity treatments.