Time-restricted feeding prevents high-fat and high-cholesterol diet-induced obesity but fails to ameliorate atherosclerosis in apolipoprotein E-knockout mice

Exp Anim. 2021 May 13;70(2):194-202. doi: 10.1538/expanim.20-0112. Epub 2020 Dec 3.


One of the leading risk factors for atherosclerosis is obesity, which is commonly caused by a nutrient-rich Western-style diet, sedentary behaviors, and shift work. Time-restricted (TR) feeding and intermittent fasting are both known to prevent overweight and adiposity, improve glucose tolerance, and decrease plasma cholesterol in high-fat diet-induced obese mice. Here we examined the overall effects of TR feeding of a Western diet (fat, 40.5 Kcal%; cholesterol, 0.21 g%) using 8-week-old Apoe-/- mice. Mice were assigned into three groups: (1) an ad libitum (AL) group fed an AL Western diet, (2) a TR group with restricted access to a Western diet (15 h/day, 12:00 to 3:00 Zeitgeber time [ZT]); and (3) an Ex/TR group fed a TR Western diet and subjected to physical exercise at 12:00 ZT. Mice in the AL group gained body weight rapidly during the 14-week observation period. With TR feeding, excessive weight gain, liver adiposity, visceral fat, and brown adipose tissue volume were effectively suppressed. Although TR feeding failed to decrease Oil Red O-stained aortic plaques in Apoe-/- mice, physical exercise significantly decreased them. Neither TR feeding with exercise nor that without exercise decreased the mean area under the curve of the plasma cholesterol level or the fasting plasma glucose. Collectively, TR feeding of a Western diet prevented the development of obesity but failed to ameliorate atherosclerosis in Apoe-/- mice.

Keywords: Western-style diet; apolipoprotein E-knockout mice; atherosclerosis; obesity; time-restricted feeding.

MeSH terms

  • Animals
  • Apolipoproteins E / genetics*
  • Atherosclerosis / chemically induced
  • Atherosclerosis / prevention & control*
  • Cholesterol, Dietary / administration & dosage
  • Cholesterol, Dietary / adverse effects*
  • Diet, High-Fat / adverse effects*
  • Fasting*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / chemically induced
  • Obesity / prevention & control*


  • Apoe protein, mouse
  • Apolipoproteins E
  • Cholesterol, Dietary