LAUSR

Preclinical and clinical data suggest that body weight (i.e., body fat) is physiologically regulated, and the high heritability seen from monozy-gotic twin studies suggests a genetic basis to one ’ s defended body weight. Genome-wide association studies have found that a high pro-portion of variants that correlate with elevated body mass index are expressed in the central nervous system, signifying that the molecular predicates that likely encode for defended body weight will be found in the brain [1]. In this context, an individual integrates peripheral signals (e.g., adipokines, myokines, hepatokines) relaying the metabolic state of various tissues to the brain and reacts to maintain relatively stable weight. However, the recent increased prevalence of obesity/ overweight reveals that environmental factors must be influencing this system, and why some people are more susceptible to weight gain in a given environment is not fully understood [2]. In this issue, Fang et al. [3] present an interesting and thorough set of experiments that demonstrate how fat content in diet affects defended body weight in C57BL/6N mice. By changing the macronu-trient composition (fat and carbohydrate) of diets and undertaking switches in diet at different ages (young and adult) and for different durations (4, 8, or 24 weeks), as well as putting mice through rounds of weight gain and weight loss (yo-yo dieting), they provide strong evidence that the major driver of defended body weight in these animals is the amount of fat within the diet. The key takeaway message is that higher-fat diets (HFDs, i.e., diets with 45