Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet-induced Metabolic Disorder

Sci Rep. 2016 May 18;6:26325. doi: 10.1038/srep26325.


This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals' access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Weight
  • Diet, High-Fat / adverse effects*
  • Fatty Liver / diet therapy
  • Fatty Liver / prevention & control
  • Glucose Intolerance / diet therapy
  • Glucose Intolerance / prevention & control
  • Inflammation
  • Insulin Resistance
  • Metabolic Diseases / diet therapy*
  • Metabolic Diseases / prevention & control
  • Mice, Inbred C57BL
  • Mice, Obese
  • PPAR alpha
  • PPAR gamma


  • PPAR alpha
  • PPAR gamma