Effect of a High-Fat Diet and Occupational Exposure in Different Rat Strains on Lung and Systemic Responses: Examination of the Exposome in an Animal Model

2019 ◽  
Vol 174 (1) ◽  
pp. 100-111 ◽  
Author(s):  
James M Antonini ◽  
Vamsi Kodali ◽  
Mohammad Shoeb ◽  
Michael Kashon ◽  
Katherine A Roach ◽  
...  

Abstract The exposome is the measure of all exposures of an individual in a lifetime and how those exposures relate to health. The goal was to examine an experimental model integrating multiple aspects of the exposome by collecting biological samples during critical life stages of an exposed animal that are applicable to worker populations. Genetic contributions were assessed using strains of male rats with different genetic backgrounds (Fischer-344, Sprague Dawley, and Brown-Norway) maintained on a regular or high-fat diet for 24 weeks. At week 7 during diet maintenance, groups of rats from each strain were exposed to stainless steel welding fume (WF; 20 mg/m3 × 3 h/d × 4 days/week × 5 weeks) or air until week 12, at which time some animals were euthanized. A separate set of rats from each strain were allowed to recover from WF exposure until the end of the 24-week period. Bronchoalveolar lavage fluid and serum were collected at 7, 12, and 24 weeks to assess general health indices. Depending on animal strain, WF exposure and high-fat diet together worsened kidney toxicity as well as altered different serum enzymes and proteins. Diet had minimal interaction with WF exposure for pulmonary toxicity endpoints. Experimental factors of diet, exposure, and strain were all important, depending on the health outcome measured. Exposure had the most significant influence related to pulmonary responses. Strain was the most significant contributor regarding the other health indices examined, indicating that genetic differences possibly drive the exposome effect in each strain.

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Astrid Skovmand ◽  
Aaron Erdely ◽  
James M. Antonini ◽  
Timothy R. Nurkiewicz ◽  
Mohammad Shoeb ◽  
...  

Abstract Background Previous studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m3 of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7–12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24). Results At week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFα). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet. Conclusion Exposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hye-Kyung Choi ◽  
Eun-Kyung Won ◽  
Young Pyo Jang ◽  
Se-Young Choung

The antiobesity effects ofCodonopsis lanceolata(CL) were evaluated in a high-calorie/high-fat-diet (HFD-) induced obesity rat model and 3T3-L1 cells. The Sprague-Dawley male rats were fed a normal diet (ND) or a HFD for a period of 12 weeks. The rats were subdivided into groups: ND, ND + wildCodonopsis lanceolata(wCL) (900 mg/kg/day, p.o.), ND + cultivatedCodonopsis lanceolata(cCL) (900 mg/kg/day, p.o.), HFD, HFD + wCL (100, 300, or 900 mg/kg/day, p.o.), HFD + cCL (100, 300, or 900 mg/kg/day, p.o.), and HFD + sibutramine. The body weight gains of the administered HFD + CL (wCL or CCL) were lower than those of the rats fed with only the HFD group. Moreover, the weight of adipose pads and the serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol in the group administered HDL + CL were significantly lower than in the HFD group. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR). Treatment of 3T3-L1 cells with wCL inhibited lipid accumulation and expression of C/EBPαand PPARγ. These results suggest that CL has a great potential as a functional food with anti-obesity effects and as a therapeutic alternative in the treatment of obesity.


1984 ◽  
Vol 56 (1) ◽  
pp. 78-83 ◽  
Author(s):  
W. C. Miller ◽  
G. R. Bryce ◽  
R. K. Conlee

Eighty-seven male Sprague-Dawley rats (245–300 g) were randomly assigned to one of two experimental groups. The first group consumed a diet high in fat and low in carbohydrate (LCD), whereas the second group ate a normal diet (ND). After either 1 or 5 wk on the diets, rats from each group were killed either before or after an exhausting run on a rodent treadmill (35 m X min-1, 0% grade). The LCD animals ran significantly longer before exhaustion at both week 1 (44.9 +/- 5.1 vs. 41.6 +/- 4.2 min) and week 5 (47.1 +/- 3.6 vs. 35.5 +/- 3.1 min) (P less than 0.05). Adaptations to the LCD included lower muscle and liver glycogen content, decreased rate of glycogen breakdown during exercise, decreased lactate production, and elevated blood ketone levels. In addition to these substrate changes, the LCD caused increased enzyme activities of muscular 3-hydroxyacyl-CoA dehydrogenase (35–110%) and citrate synthase (15–20%). These data indicate that rats exposed to a high-fat diet are capable of prolonged intense exercise in spite of limited glycogen stores. This improved capacity for exercise appears to be partially the result of muscular adaptations to the diet, which apparently increase the ability to oxidize fat and concomitantly spare glycogen.


2000 ◽  
Vol 279 (5) ◽  
pp. E1088-E1096 ◽  
Author(s):  
James R. Levy ◽  
John Lesko ◽  
Richard J. Krieg ◽  
Robert A. Adler ◽  
Wayne Stevens

The secretion of leptin is dually regulated. In fasting animals, plasma leptin concentrations reflect body fat stores, whereas the incremental leptin response to fasting or refeeding most likely reflects insulin-mediated energy flux and metabolism within adipocytes. Impaired secretion of leptin in either pathway could result in obesity. We therefore measured plasma leptin concentrations in fasted animals and plasma leptin concentrations after an intravenous glucose infusion in a rat model of obesity. Young Sprague-Dawley (S-D) and Fischer 344 (F344) rats had similar percent body fat and fasting glucose and fasting leptin concentrations. However, F344 animals had higher insulin concentrations and leptin responses to intravenous glucose than did the S-D animals. The animals were then fed a control or high-fat diet for 6 wk. High-fat fed animals gained more weight and body fat than did the control fed animals. Control and high-fat fed F344 animals gained ∼40% ( P < 0.0001) more weight and >100% ( P < 0.01) more body fat than did the S-D animals. Fasting leptin concentrations and leptin concentrations after intravenous glucose infusions and feeding were more than double ( P < 0.05) in F344 animals compared with S-D animals. Whether an animal is fed a control or high-fat diet had little effect on the leptin response to intravenous glucose. In conclusion, young, lean F344 animals, before the onset of obesity, demonstrated a greater acute leptin response to intravenous glucose than similarly lean S-D animals. After a 6-wk diet, F344 animals had a greater percent increase in body weight and insulin resistance and exhibited higher fasting leptin concentrations and a greater absolute leptin response to intravenous glucose compared with the S-D animals. The chronic diet (control or high fat) had little impact on the acute leptin response to intravenous glucose. F344 animals exhibit leptin resistance in young, lean animals and after aging and fat accumulation.


2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Othman ZA ◽  
Wan ghazali WS ◽  
Noordin L ◽  
Omar N ◽  
Mohd. Yusof NA ◽  
...  

Introduction: Orlistat is a widely used drug in treating obesity as it promotes weight reduction. The aim of this study was to determine the protective effects of orlistat (10 mg/kg/day) on cardiovascular parameters and oxidative stress biomarkers in high-fat diet (HFD)-induced obese rats. Methods: Twenty-four male rats Sprague Dawley rats were divided into three groups and fed with normal diet (N), HFD and HFD with orlistat (HFD+O). Orlistat was administered daily by oral gavage and after six weeks, all rats were sacrificed. Results: Administration of orlistat along with HFD (HFD+O) has brought significant decreases in Lee obesity index and LDL level compared to HFD group. Activities of cardiac superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were significantly higher, whereas level of oxidised LDL was significantly lower in HFD+O group compared to HFD group. HFD group had significantly higher necrotic patch area in myocardium while minimal histological changes were seen in HFD+O group. Conclusion: This study may suggest that administration of orlistat at 10 mg/kg/day for 6 weeks may have protective effects against the changes on Lee obesity index, lipid profiles, cardiac oxidative stress biomarkers and histology of myocardium in HFD-induced obese rats possibly through its hypolipidaemic and antioxidant actions.


2017 ◽  
Vol 41 (2) ◽  
pp. 598-608 ◽  
Author(s):  
Xiangrong Cui ◽  
Chunlan Long ◽  
Jing Zhu ◽  
Jie Tian

Background: Statins can reduce reproductive damage induced by obesity or high-fat diet (HFD), but the specific regulatory mechanisms are largely unknown. Since mTOR/p70s6k sinaling promotes spermatogonia proliferation and spermatogenesis, we hypothesized that this pathway will be involved in the protective effects of statin in HFD-induced reproductive dysfunction. Methods: Male Sprague Dawley rats (3 weeks old) were randomly divided into a control group (standard diet), HFD group, and a fluvastatin group (HFD + fluvastatin at 6mg/kg, once daily by oral gavage). After 8 weeks, body weight was obtain and rats were sacrificed. Weights of the testes, gross morphology, sperm parameters, circulating levels of sex hormones, lipid levels, and tissue mTOR, p-P70s6k were measured. Another set of male rats were treated with rapamycin or vehicle. Flow cytometry was used to detect the spermatogonia marker c-kit and cell cycle. p-P70s6k expression was analyzed by Western blot. Results: HFD not only results in rat obesity but also leads to spermatogenetic damage and fluvastatin was able to partially block the effects of HFD. Fluvastatin also partially reversed the suppression of mTOR and p-p70s6k expresson. Conclusion: Our data suggest that fluvastatin has protective effects on reproductive function in obese male rats most probably through enhanced signaling of mTOR.


2016 ◽  
Vol 12 (3) ◽  
pp. 116
Author(s):  
Novian Swasono Hadi ◽  
Arta Farmawati ◽  
Ahmad Ghozali

Background: Lifestyle changes with high-fat food consumption is one of the factors the risks of cardiovascular diseases like of coronary heart disease and atherosclerosis. A healthy diet and a balanced diet and consume foods that contain lots of antioxidants is one of the effective ways to prevent hyperlipidemia. Mung bean sprouts have properties that neutralize free radicals cause Hyperlipidemia and cardiovascular diseases because it is an antioxidant compound.Objective: The aim of this study was to determinate the effect of mung bean sprouts (Phaseolus radiatus (L)) to blood pressure and histopathology aorta of Sprague-Dawley male rats.Method: The type of study was experimental research using pre-post test controlled group design for blood pressure variable and post test only controlled group design histopathology aorta. The thirty-five of Sprague-Dawley male rats was eight weeks divided into 5 groups. The first group was given standard diet, group 2 was given a hight fat diet, the third group was given a high-fat diet and mung bean sprout 0,67 gram, group 4 was given a high-fat diet and mung bean 1,34 gram, and group 5 was given a high-fat diet and vitamin E doses of 23 IU.Results: Result of this study showed that after 4 weeks of treatment, increased in blood pressure systole in the given of  high fat diet higher than group who were given a high fat diet and mung bean sprout and also on group who were given high fat diet and vitamin E, but there is no difference effect a decrease in blood pressure between the provision of mung bean sprouts and vitamin E (p>0,05). Statistical analysis to thick the wall the aorta show the similarity meaningful in all the treatment group, it can be said that overall thick the wall the aorta in this research is not different.Conclusion: A dose of mung bean sprout 0,67 g is optimal doses in preventing a rise in blood pressure and prevent alterations histopathology Sprague-Dawley male rats.


Metabolism ◽  
2021 ◽  
Vol 116 ◽  
pp. 154497
Author(s):  
Elif Günalan ◽  
Meyli Ezgi Karagöz ◽  
Bayram Yılmaz ◽  
Burcu Gemici

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