Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague–Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction

Keenan, Kevin P.; Hoe, Chao-Min; Mixson, Lori; Mccoy, Carol L.; Coleman, John B.; Mattson, Britta A.; Ballam, Gordon A.; Gumprecht, Laura A.; Soper, Keith A.

doi:10.1080/01926230500311222

Cited by 32 publications

(37 citation statements)

References 99 publications

(505 reference statements)

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“…We do not expect our food restriction regime to have had any adverse effects on the animal's well-being, since none of our animals lost more than 10% of their initial body weight. Food restriction of similar levels has been shown to decrease organ pathology and increase longevity in rats (Keenan et al 2005;Rowland 2007). Additionally, food restriction has recently been suggested to affect learning and performance in memory and discrimination tasks (Makowiecki et al 2012;Kuhla et al 2013;Talhati et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Motivational state, reward value, and Pavlovian cues differentially affect skilled forelimb grasping in rats

2016

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Motor skills represent high-precision movements performed at optimal speed and accuracy. Such motor skills are learned with practice over time. Besides practice, effects of motivation have also been shown to influence speed and accuracy of movements, suggesting that fast movements are performed to maximize gained reward over time as noted in previous studies. In rodents, skilled motor performance has been successfully modeled with the skilled grasping task, in which animals use their forepaw to grasp for sugar pellet rewards through a narrow window. Using sugar pellets, the skilled grasping task is inherently tied to motivation processes. In the present study, we performed three experiments modulating animals' motivation during skilled grasping by changing the motivational state, presenting different reward value ratios, and displaying Pavlovian stimuli. We found in all three studies that motivation affected the speed of skilled grasping movements, with the strongest effects seen due to motivational state and reward value. Furthermore, accuracy of the movement, measured in success rate, showed a strong dependence on motivational state as well. Pavlovian cues had only minor effects on skilled grasping, but results indicate an inverse Pavlovian-instrumental transfer effect on movement speed. These findings have broad implications considering the increasing use of skilled grasping in studies of motor system structure, function, and recovery after injuries.

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Section: Discussionmentioning

confidence: 99%

Motivational state, reward value, and Pavlovian cues differentially affect skilled forelimb grasping in rats

2016

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“…Rebounding of serum testosterone levels and accessory sex organ weights also occurred when FR was initiated at ten weeks of age and continued for twenty-four weeks (Glass et al 1986). Therefore, in the course of a two-year carcinogenicity study, reduced food consumption will not have a negative impact on the male reproductive system (Keenan et al 2005;Seki et al 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Food restriction (FR) in rat chronic toxicity studies prevents the development of obesity and delays the onset of inherent disease (Keenan et al 1999;Keenan et al 2005;Molon-Noblot et al 2003;Nold et al 2001). Food restriction is usually implemented when rats are approximately eight weeks of age, prior to full sexual maturity.…”

Section: Introductionmentioning

confidence: 99%

Effects of Food Restriction on Testis and Accessory Sex Glands in Maturing Rats

et al. 2008

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Reduced food consumption and associated lower body weights may occur in subacute toxicity studies. The short-term effects of food restriction (FR) on body and reproductive organ weights, hormones, and testis histology were assessed in Sprague-Dawley rats fed 20% to 36% less (21 g feed/day) than rats fed ad libitum (AL) starting at six, eight, ten, or twelve weeks of age for two or six weeks. Body weight and relative seminal vesicle, ventral prostate, and/or epididymis weights were reduced in rats FR for two or six weeks. Degeneration of stage VII pachytene spermatocytes was seen in rats FR for six weeks when initiated at eight, ten, and twelve weeks of age. Plasma testosterone concentrations were lower in rats FR at ages six to eight weeks, eight to ten weeks, six to twelve weeks, and eight to fourteen weeks. Luteinizing hormone was not statistically different in FR rats compared with AL counterparts. Therefore, duration of lower food intake had a greater impact on spermatogenesis, whereas a younger initial age of lower food intake was more influential on testosterone levels. These interactions are important in the interpretation of subacute toxicology studies employing FR or when test articles lower food consumption relative to AL-fed rats.

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“…Ad libitum feeding, which is the standard approach in carcinogenicity bioassays, has been shown clearly to exacerbate poor survival amongst standard strains. In contrast, moderate dietary restriction of approximately 25-35% results in a better toxicology model by significantly improving survival, controlling adult body weight and obesity, reducing the onset, severity, and morbidity of age-related renal, endocrine, metabolic, and cardiac diseases, reduces inter-study variability, increases treatment exposure time, and increases the ability to distinguish true treatment effects from spontaneous ageing (Keenan et al, 2005). Therefore, while food restriction should be considered, it is infrequently used for a variety of logistical reasons that result in increased cost.…”

Section: Food Restrictionmentioning

confidence: 99%