and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats.
As obesity continues to grow across the world, better understanding of the disease, treatments, and outcomes becomes increasingly important. Animal models used to study these aspects of obesity have 3 phases: experimental (EXP), caloric restriction (CR), and weight regain (WR). For this study an ad libitum high-fat diet (HFD) was used to induce hyperphagia and weight gain in Sprague-Dawley rats in the experimental period. Rats then transitioned to a chow (CH) diet and energy intake (EI; kcal/day) was reduced 40-60% during the caloric restriction period. In weight regain, rats were given chow ad libitum. This protocol was run 3 times, once every academic school year (2017-2018, 2018-2019, and 2019-2020). Sample sizes listed in the order of high fat (HF) rats then chow (CH) rats for each year were as follows: 2017-2018 (n=11, n=8), 2018-2019 (n=12, n=8), 2019-2020 (n=14, n=10). Analysis of energy intake was performed on the first week of the experimental phase and the first week of the weight regain phase. <br/><br/>HF EXP rats showed hyperphagic average daily EIs compared to CH EXP rats for all 3 years (p<0.01-0.0001). HF WR rats were similar to CH WR rats in all applicable years in terms of average daily EI. However, both HF WR and CH WR rats were hyperphagic. HFD caused hyperphagia to be highest at the beginning of the first week of EXP and then EI decreased significantly as days went by. However, in WR, hyperphagia (HF WR and CH WR) was flat throughout the week. Obesity prone (OP) rats during EXP had similar EI behavior to obesity resistant (OR) rats during EXP within the same year. During WR though, OP rats had significantly greater average daily EI (p<0.05-0.001) compared to WR OR rats within the same year for 2 out of the 3 years. <br/><br/>These results suggest that HFD induces hyperphagia during weight gain. In weight regain, where HFD is absent, HF rats and CH rats are both hyperphagic. This suggests that WR induces hyperphagia in both rat groups. WR also induces a greater increase in EI for OP rats compared to OR rats. Therefore, hyperphagia seems to be driven by 2 mechanisms (HFD and WR). The profiles of the responses are different however. HFD induces hyperphagia that decreases over the first week and the level of hyperphagia is similar between OP and OR rats. WR induces hyperphagia that remains stable in the first week and is more pronounced in OP rats compared to OR rats.