Alternate-day high fat-normal chow diet

Introduction

Obesity, defined as body mass index (BMI) equal to or greater than 30, is a global public health problem. In 2016, 650 million adults, approximately 13% of the world-wide population, were obese. The health consequences of obesity include type 2 diabetes, cardiovascular diseases, musculoskeletal problems, and cancer, among other conditions (World Health Organization, 2021). Most obesity can be attributed to an imbalance between energy intake and expenditure.^1,2

It is well recognized that a high-fat diet (HFD) or a high-fat high-sugar diet causes obesity and related metabolic diseases in rodents, primates, and humans.^3–7 Moreover, overnutrition stimulates intestinal epithelial proliferation and is partially responsible for diet-induced obesity.^4,8 Caloric restriction, reducing food intake without malnutrition, is an effective regimen for body weight control and has received considerable research attention.^9–11 Recently, intermittent fasting (IF) with alternating dietary regimens was shown to be effective for weight loss in overweight and obese patients^12–15 and in rodent studies.^16,17 Among the various IF regimens, alternate-day fasting (ADF) is most frequently studied in rodents and showed profound metabolic benefits through multiple signaling pathways.^12,17–20 Although previous studies have suggested that it is the gut microbiome most implicated in ADF-induced weight control,^21,22 one would expect concomitant changes in the small intestine, the…