Evolution and obesity: resistance of obese-prone rats to a challenge of food restriction and wheel running

Abstract

The adaptive hypothesis that an obese-prone genotype confers a fitness advantage when challenged with food restriction and food-related locomotion was tested using a rat model. Juvenile (35-40 days) and adolescent (45-50 days) JCR:LA-cp rats, obese prone (cp/cp) and lean prone ( þ /?), were exposed to 1.5 h daily meals and 22.5 h of voluntary wheel running, a procedure that normally leads to self-starvation. Genotype had a dramatic effect on survival of rats when exposed to the challenge of food restriction and wheel running. Although similar in initial body weight, obese-prone juveniles survived twice as long, and ran three times as far, as their lean-prone counterparts. Biochemical measures indicated that young obese-prone animals maintained blood glucose and fat mass, whereas lean-prone rats depleted these energy reserves. Corticosterone concentration indicated that obese-prone juveniles exhibited a lower stress response to the survival challenge than lean-prone rats, possibly due to lower energy demands and greater energy reserves. Collectively, the findings support the hypothesis that an obese-prone genotype provides a fitness advantage when food supply is inadequate, but is deleterious during periods of food surfeit, such as the energy-rich food environment of prosperous and developing societies worldwide. Keywords: adaptation; food restriction; wheel running; genotype; survival Obesity is portrayed as a weight disorder with negative connotations of susceptibility to diabetes, 1 the metabolic syndrome, 2 heart disease 3 and cancer(s). 4 The modern clinical perspective links obesity to poor health, a shortened life span and to many sociopsychological and lifestyle disorders. An evolutionary perspective, in contrast, views obesity as resulting from variation in genotype and an environment with high-energy-dense food(s). One possibility is that the obese-prone genotype is nonadaptiveFresulting from a coincidence of genetic drift and the high-energy foods of modern humans.5 Alternatively, the obese-prone genotype may be a consequence of adaptation, and obesity is a phenotypic expression of an interaction between genotype (obese-prone vs lean-prone) and environment (high-/lowenergy food supply). The 'thrifty gene' theory of obesity is one form of the adaptive hypothesis. The theory explains how genes favor the efficient use of energy stores in times of feast followed by famine, and result in obesity in the food-rich environment of prosperous societies.6,7Our formulation of the adaptive hypothesis proposes that the obese-prone genotype confers an advantage under conditions of unpredictable changes in food supplyF allowing for storage and conservation of energy and increased foraging during periods of food depletion. In the laboratory, rats on food restriction with the opportunity to (wheel) run show activity anorexiaFa vicious cycle of suppressed food intake, declining body weight and escalating wheel activity leading to starvation and death. 8,9 Compared with lean strains, rats from an obese-prone strain surviv...

Prior caloric restriction increases survival of prepubertal obese- and PCOS-prone rats exposed to a challenge of time-limited feeding and physical activity

“…On average, O/PCOS-prone rats raised on free access to food lasted 2.4 times longer than Lean-FF rats under the AAC, replicating our recent findings in obese-prone, male JCR rats (29). Age-matched JCR female rats, prone to obesity and PCOS, survived longer in the AAC than male obese-prone rats, demonstrating an additional survival benefit of the PCOS genotype.…”

“…rats. This supports the notion that genotype and food environment contribute to survival during unpredictable periods of food shortage (29). However, less is known about the survival benefit of a PCOS background associated with the obese-prone (cp/cp) genotype in suboptimal nutritional environments.…”

“…The after-before difference in plasma corticosterone levels, an index of HPA axis reactivity, was 2.3 times lower in O/PCOSprone rats (ϩ40.59 nmol/l) than lean-prone animals (ϩ94.09 nmol/l), indicating an inverse relationship between stress and survival (5,29). Thus O/PCOS-prone, female rats have highenergy reserves, low-energy expenditure, and reduced HPA axis-reactivity factors, favoring prolonged survival in the AAC.…”

Dietary Interventions, Cardiovascular Aging, and Disease

“…60,61 Levels of plasma aldosterone, renin, and norepinephrine follow similar patterns to those observed in humans with CHF. Although multiple studies have demonstrated the beneficial effects of physical activity, CR, and body weight reduction on survival, 62,63 there is a lack of information regarding the effects of fasting in this model. The outcome of such a study would be of great clinical impact considering that coronary heart disease (CHD), hypertension and, in the long term, the use of certain chemotherapy drugs can lead to the development of CHF.…”

Natural Science and Learning: A Review of Behavior Analysis and Learning (5th Edition)

“…The concept of reinforcement is thoroughly established in earlier chapters, so this section is wellsuited to support the concept through discussion of ontogenetic adaptability (Glenn 1991), computer analogs (McDowell and Popa 2010), neuroscience (Donahoe 2002), and genetics (Pierce et al 2010). Finally, selection on a cultural level is introduced and discussed.…”