System Wide Benefits of Intermeal Fasting by Autophagy


This study appeared in the journal Cell Metabolism

Key words

Autophagy – essentially, a “cellular cleaning process” critical for proper cellular function. This quality control mechanism ensures that senescent or non-functional cells are cleared out and prevents accumulation of cellular damage. Aging is associated in a compromised ability for the body to regulate this “quality control” mechanism which may lead to buildup of damage and organ dysfunction.

Brief recap

This study demonstrates that consuming two meals a day (Intermittent twice-a-day or ITAD), with complete fasting (food restriction) in between meals is enough to lower blood glucose and lipid levels. Twice a day feeding is a simple approach that activates the cell-cleaning system known as autophagy in the liver, fat cells, brain, and muscle – by which it may help to prevent metabolic diseases such as obesity and diabetes.


What are the highlights of this study?

  • Twice-a-day feeding with the same number of calories as an ad libidum diet favorably impacts autophagy in multiple tissue systems
  • ITAD also promotes metabolic benefits in multiple tissue systems
  • ITAD prevented age- and obesity-related metabolic defects
  • Benefits of ITAD are mediated by the tissue-specific effects of autophagy in response to the feeding protocol

Study protocol

Two groups of mice were fed isocaloric diets (consisting of the same number of calories/energy) in either a (1) twice-a-day feeding fashion where food was only provided in two 2-hour windows each day (8-10 am and 5-7pm) or (2) non-restricted feeding condition (control). The ad libidum fed mice had access to food throughout the 24-hour circadian cycle. Both cohorts of mice were group housed. ITAD group and ad-lib control (CON) group contained equal numbers of age- and sex-matched littermate mice.


  • In as early as 3 months, ITAD fed mice demonstrated a progressive loss in body fat and a proportionate increase in lean mass – indicating that partitioning daily calories into two 2-hour periods is sufficient to induce favorable changes in body composition.
  • ITAD fed mice demonstrated enhanced tissue-wide increases in autophagy-elated genes
  • ITAD fed mice displayed an increase in leptin sensitivity (hunger hormone) in white-adipose tissue. Additionally, decreased adipocyte size and increased energy expenditure indicated increased fat utilization in ITAD fed mice
  • Markers of anti-inflammatory macrophages increased in ITAD fed mice
  • ITAD fed mice demonstrated muscle-cell properties characteristic of cell proliferation and regeneration, as well as an increase in Type IIB (fast-twitch) muscle fibers, with no changes in type I fiber content – indicating a preserved skeletal muscle phenotype that is typically lost with age.
  • ITAD feeding suppressed liver gluconeogenesis (production of glucose) and activated fat breakdown/reduced fat cell production and hence decreased liver lipid levels.
  • ITAD feeding in older (24-month old) mice was able to reduce hyperlipidemia and potentially lower overall cardiovascular disease risk with aging
  • ITAD prevented the age-associated loss of V02,VC02, and energy expenditure rate, and improved glucose clearance in aged and obese mice



  • Twice-a-day feeding may prevent metabolic defects when the meals are portioned to occur at 2 separate intervals during the circadian period without the need for caloric restriction or changing the type of food consumed



Cell Metab. 2017 Oct 24. pii: S1550-4131(17)30608-3

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