Time‐restricted feeding for prevention and treatment of cardiometabolic disorders

Abstract

The soaring prevalence of obesity and diabetes is associated with an increase in comorbidities, including elevated risk for cardiovascular diseases (CVDs). CVDs continue to be among the leading causes of death and disability in the United States. While increased nutritional intake from an energy-dense diet is known to disrupt metabolic homeostasis and contributes to the disease risk, circadian rhythm disruption is emerging as a new risk factor for CVD. Circadian rhythms coordinate cardiovascular health via temporal control of organismal metabolism and physiology. Thus, interventions that improve circadian rhythms are prospective entry points to mitigate cardiometabolic disease risk. Although light is a strong modulator of the neural circadian clock, time of food intake is emerging as a dominant agent that affects circadian clocks in metabolic organs. We discovered that imposing a time-restricted feeding (TRF) regimen in which all caloric intakes occur consistently within ≤ 12 h every day exerts many cardiometabolic benefits. TRF prevents excessive body weight gain, improves sleep, and attenuates age- and diet-induced deterioration in cardiac performance. Using an integrative approach that combines Drosophila melanogaster (fruit fly) genetics with transcriptome analyses it was found that the beneficial effects of TRF are mediated by circadian clock, ATP-dependent TCP/TRiC/CCT chaperonin and mitochondrial electron transport chain components. Parallel studies in rodents have shown TRF reduces metabolic disease risks by maintaining metabolic homeostasis. As modern humans continue to live under extended periods of wakefulness and ingestion events, daily eating pattern offers a new potential target for lifestyle intervention to reduce CVD risk.

Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington’s Disease

“…Prior work in Drosophila has also demonstrated the benefits of TRF in ameliorating age-related cardiovascular decline (Melkani and Panda, 2017). In this model, TRF downregulates expression of gene involved in mitochondrial electron transport while increasing expression of a cytoplasmic chaperonin (Gill et al, 2015).…”

TRiC/CCT chaperonins are essential for maintaining myofibril organization, cardiac physiological rhythm, and lifespan

“…In our Drosophila melanogaster heart RNA‐sequencing analysis, we observed consistent cardiac‐specific upregulation of CCT components under time‐restricted feeding (TRF) . Imposing feeding/fasting rhythms with TRF paradigm attenuates age‐ and diet‐induced cardiac dysfunction without altering calories intake . Under TRF regimen, all caloric intakes occur within a consistent ≤ 12‐h every day whereas for the Ad libitum feeding (ALF) group, food is available 24 h·day −1 .…”

Altered mitochondrial metabolism in the insulin‐resistant heart

“…For example fruit flies that were put on time‐restricted feeding during their active phase showed improved cardiac physiology, as indicated by ex vivo heart period and arrhythmia index, together with altered cardiac gene expression, with circadian clock and electron transfer system (ETS) genes ranking as top clusters . The beneficial effects of time‐restricted feeding on the heart are understood to be at least partly mediated by ATP‐dependent chaperonin and mitochondrial ETS components . Nineteen different genes which encode the mitochondrial ETS were downregulated by 10%‐20%, whereas seven out of eight components of an ATP‐dependent chaperonin were upregulated in the hearts of rats on a time‐restricted diet …”

“…The beneficial effects of time‐restricted feeding on the heart are understood to be at least partly mediated by ATP‐dependent chaperonin and mitochondrial ETS components . Nineteen different genes which encode the mitochondrial ETS were downregulated by 10%‐20%, whereas seven out of eight components of an ATP‐dependent chaperonin were upregulated in the hearts of rats on a time‐restricted diet …”