Long-term obesogenic diet leads to metabolic phenotypes which are not exacerbated by catch-up growth in zebrafish

Obesity is a world wide problem and evidence suggests, that early lifetime undernourishment of caloric restirction predispose an organism for obesity and metabolic syndrome. We have raised two cohorts of zebrafish in an obesogenic environment (DIO) and compared several metabolic markers with fish raised under caloric restriction (CR) or fish shifted from CR to DIO at different periods in their life. We have looked morphologically at standard length and weight and found that fish on DIO grow faster in both axes. Fish shifted from CR to DIO show catch-up growth and not compensatory growth when shifted at one month, 3 months or 9 months of age. We have further characterized central agrp expression and hyperphagia, adipose tissue by histology as well as uCT imaging, hepatic histology, metabolic rate mitochondrial function as well as feeding induced glucose levels. We find that fish in an obesogenic environment develop markers of obesity which are not exacerbated by ealry lifetime food restriction.