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Objective Previous studies on the pathology of obesity and obesity‐induced metabolic disorders utilized genetically modified obese rat models. To better mimic the onset and the physiology of obesity in humans, the use of diet‐induced obese rat models is lacking. Therefore, the purpose of this study is to induce obesity in Sprague Dawley rats by administering a high fat (HF) diet and to further investigate the effects of obesity on blood glucose and ketone concentrations as well as locomotor and mental activities as indicators of fatigue. Methods Fifty‐four 7‐week‐old male Sprague Dawley rats were randomized into either a high‐fat diet (HFD) group (n=28) or a standard diet (SD) group (n=26). All rats were housed in individual cages under controlled laboratory conditions and had access to food and water ad libitum. The HFD group received a HF diet (60% fat, 20% CHO, and 20% Pr) for six weeks, while the SD group received a standard diet (17% fat, 56% CHO, 27% Pr). Body weight (BW) was measured weekly and blood glucose and ketones were measured twice a week for 6 weeks. The open field test (OF) was conducted daily for 8 days in week 5, followed by Novel object recognition (NOR) testing at 4 separate days during week 6. Results Both groups gained weight from week 1 to week 6 (HFD: 223.0±16.2g vs. 387.7±23.6g, p<0.001; at week 1 vs. week 6, respectively, SD: 215.0±15.9g vs. 361.5±23.6g, p<0.001; at week 1 vs. week 6, respectively). However, the average within‐subject BW gain was greater in the HFD compared to the SD (168.1±21.6g vs 130.1±16.9g, p<0.001; HFD vs. SD, respectively). Although the average glucose levels were not different between the two groups throughout the study, the HFD showed higher fluctuations of blood glucose levels and at week 4 they had higher glucose levels than the SD (104.1±11.2mg/dL vs. 96.6±6.9mg/dL, p=0.005; for HFD vs. SD, respectively). Ketone levels were not different between the two groups. Although there were no overall differences in OF and NOR test results in HFD vs. SD, the difference between the recognition time of the familiar vs. the novel object in the HFD tended to be smaller than that of the SD at all 4 days of NOR testing (p=ns). Conclusions The HF diet results in significant weight gain consistent with obesity in the majority of rats within a 6‐week period of receiving the diet. Overall, diet‐induced obesity was not found to have adverse effects on glucose and ketone levels. However, it might negatively affect memory and lead to mental fatigue in rats.

Sex differentiation of a rat brain occurs during the perinatal period (four days prior to and four days after birth). The undifferentiated brain becomes a female brain unless it is exposed to testosterone (T) which gets metabolized to 17β‐estradiol (E2) and dihydrotestosterone (DHT). While aromatase converts T to E2, 5α‐reductase converts T to DHT. 17β‐estradiol exerts its effects by binding to an estrogen receptor (ER) whereas DHT via an androgen receptor (AR). We tested the significance of DHT and E2 during the organizational phase in the differentiation of the rat brain. During the last four days of pregnancy, seven timed‐pregnant rats received either the vehicle (5% ethanol and 95% sesame oil), exemestane (Aromasin; 4mg/kg/ml), or flutamide (20 mg/kg/ml) subcutaneously. Pups from each group continued to receive their specific treatments during the first four days after birth. From postnatal day 65, these animals were subjected to open field (OF), spatial working memory, and sexual motivation (SM) tests. Male rats receiving flutamide exhibited a significant increase in exploratory behavior. Additionally, male rats receiving exemestane exhibited significantly greater interest in the estrus rat compared to the control group. In conclusion, under AR blockade, where E2 becomes the main gonadal hormone, improvements in exploratory behavior in male rats were observed. Moreover, when exemestane was used to block E2 conversion, and DHT becomes the main gonadal hormone, increased SM in male rats was observed. Thus, the presence of both E2 and DHT during organizational phase appears to be essential for normal socio‐sexual and exploratory behaviors.

Obesity is a major contributing factor in the development of many chronic conditions such as type 2 diabetes and hypertension. Intermittent fasting (IF) isa pattern of feeding that cycles between periods of fasting and eating. It allows eating within a specific time period, and fast during the rest of the day. Intermittent fasting appears to be a promising approach to prevent or reverse obesity. Our project involved the induction of obesity using a high fat diet (HFD; D12492‐60% kcal diet) in male Sprague Dawley rats. Blood glucose and ketone levels were measured twice a week and daily body weights were monitored. The rats being fed on the HFD gained 12% more weight than those on a standard diet (SD) and 14% weight gain compared to the growth chart of the animal supplier within seven weeks of feeding this special diet. Blood ketone and glucose levels remained unchanged between these groups. The animals with HFD, now referred to as the obese (OB) group and those with SD referred to as non‐obese (non‐OB) rats were placed on IF next. Intermittent fastingin this experiment was designed to allow animals to eat for 6 hours during their nocturnal window of time and fast during the remaining 18 hours. The OB and non‐OB groups were subdivided into five groups during the IF study: (1) OB rats on IF who were given HFD (OB‐IF‐HFD; N=3), (2) OB rats on IF given SD (OB‐IF‐SD; N=3), (3) OB rats maintained on HFD ad libitum (OB‐non‐IF; N=4), (4) non‐OB rats on IF with SD (non‐OB‐IF; N=3), and (5) non‐OB rats maintained on SD ad libitum (non‐OB‐non‐IF; N=3). Within three weeks of exposure to IF, there was a significant (p<0.05) decrease in body weight in the IF groups compared to the non‐IF groups receiving food ad libitum. However, blood ketone levels were significantly increased in the non‐OB‐IF rats compared to non‐OB‐non‐IF group, blood glucose levels were significantly decreased. A significant decrease in blood glucose levels was also noted in the OB‐IF‐SD group compared to OB‐non‐IF animals. This study suggests that HFD induces obesity as measured by body weight in approximately seven weeks, which can be reversed by subsequent practice of IF for three weeks but depends on the nature of the diet being used during IF i.e., IF‐induced weight loss with HFD is significantly less than with SD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.