Reproducibility of a High Fat Diet Induced Weight Gain Over Independent Years
Authors: Johnsson Kailin A. , Doan Ben , West Kynzie , Sayegh Jonathan , Khatib Rawaan , Herman Richard 
Published: May 2022

Susceptibility to dietary‐induced excessive weight gain is a product of the interaction between genetics and the environment (e.g., high fat diet, HFD). Unfortunately, research on the effects of a HFD has been confounded by uncontrolled obesogenic environments. Thus, this study investigated the reproducibility of weight gain and energy intake over 3 independent consecutive years with exposure to a tightly regulated obesogenic environment: male, outbred Sprague‐Dawley rats, 140‐160g, identical macronutrient and fatty acid composition with a caloric density of 5.24 kcal/g for 8‐wk periods. A CHOW diet which is lower in fat (3.1 kcal/g) served as a standard control. Daily data was accrued to determine means and standard deviations (SDs) of peak cumulative (additive weekly) and average periodic (isolated weekly) values, showing weight gain in rats fed a HFD in years 2018 (n=11), 2019 (n=12), and 2020 (n=14) resembled (insignificant) each other. This response was not observed with energy intake data. When heterogeneously distributed weight gain values in the HFD population were separated into tertiles, the lower and upper tertiles were designated as obesity resistant (OR) and obesity prone (OP), respectively. Both OP and OR means and SDs of weight gain resembled each other between the 3 years when studied under similar cumulative and periodic conditions whereas energy intake values did not. Percentage differences in weight gain between the 3 years under cumulative and periodic conditions were: (1) 3‐8% for HFD rats for both conditions, (2) 3‐7% and 1‐5% for OP rats, 0‐10% and 0‐12% for OR rats, respectively. Between the 3 years, the mean and SDs of feeding efficiency (FE; weight gain/ energy intake), of HFD rats were insignificant; the least variability between the years (1‐3%) was observed in OP rats. Within each year, weight gain values between HFD and CHOW rats under both conditions were insignificant except for year 2020 under cumulative conditions; weight gain for OP rats was significantly greater than OR rats (~ 25‐35%) under cumulative conditions. Under periodic condition, all rat populations exhibited significant maximal weight gain values at week 1, promptly decaying by 40‐50% at week 4 with significance between week 1‐2 and 2‐3; all values decayed to insignificance between contiguous weeks 3‐8. This periodic profile implied that the significant ascending (augmenting) weekly values associated with cumulative profiling could be misrepresenting the nature of weight gain when cross‐sectional analysis of body weight is evaluated. Pearson correlation analysis of weight gain vs. energy intake among HFD rats showed that, despite a significant slope, 53% of the variability in weight gain could be explained by the variation in energy intake values.ConclusionConsidering a history of polygenic patterns of inheritance in HFD‐fed rats, and the use of multiple litters in this study, weight gain and FE of HFD, OP and OR rats was perpetuated (reproduced) over 3 independent years, suggesting certain combination of alleles were obesogenic, the latter perhaps contributing to set‐point control.