High and low activity rats: Elevated intrinsic physical activity drives resistance to diet‐induced obesity in non‐bred rats

Perez‐Leighton, Claudio E.; Boland, Kelsey; Billington, Charles J.; Kotz, Catherine M.

doi:10.1002/oby.20045

Cited by 37 publications

(45 citation statements)

References 38 publications

(58 reference statements)

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“…However, kCals burned during periods of inactivity (Resting EE) was also increased; suggesting that other mechanisms for EE were activated in addition to SPA. Thermogenesis from brown adipose tissue activation may be involved (8,23), or increased Resting EE could be a carryover effect from SPA and Active EE, akin to post-exercise thermogenesis. Altered patterns of food intake could have resulted in changes in the thermic effects of food that were captured in Resting EE.…”

Section: Discussionmentioning

confidence: 99%

“…Orexin modulates a number of physiological processes intricately connected to body weight, notably spontaneous physical activity (SPA) and caloric intake (2–5). Humans and animals deficient in orexin exhibit reduced physical activity levels and elevated rates of obesity (2,6–8). In animals, when orexinergic tone is amplified, either through intracranial peptide infusions or stimulation of orexin neuron activity, increases in SPA and calories burned occurs (3,5,9,10).…”

Section: Introductionmentioning

confidence: 99%

“…In animals, when orexinergic tone is amplified, either through intracranial peptide infusions or stimulation of orexin neuron activity, increases in SPA and calories burned occurs (3,5,9,10). When administered daily for ten days, orexin protects rats against weight gain during high fat diet consumption (8,11). While these findings are promising, explicit roles of physical activity and energy expenditure (EE) in protecting against adiposity remain undefined, and the specific contribution of endogenous orexin neuron activity under obesogenic conditions is presently unknown.…”

Section: Introductionmentioning

confidence: 99%

“…In this case, the designer drug was C lozapine N - O xide (CNO), generally thought to be physiologically inert in rodents (17,18). Importantly, DREADDs allow for within-subjects experimental designs, preferred for studies measuring dependent variables with known individual variation, like SPA (8,11). …”

Section: Introductionmentioning

confidence: 99%

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Neuromodulation of orexin neurons reduces diet-induced adiposity

et al. 2017

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Background/Objectives Low levels of orexin are associated with obesity and reduced physical activity in humans and animals. Subjects/Methods Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) selectively activated orexin neurons in mouse lateral hypothalamus (LH) to measure effects on spontaneous physical activity (SPA). DREADD targeting was achieved by stereotaxic injection of AAV vectors into caudal lateral LH of heterozygous orexin Cre or C57/B6J mice. In one set of studies, excitation of orexin neurons was examined (virus: AAV2-EF1a-DIO-hM3Dq-mCherry), and test sessions began 3–4 h after light cycle onset. In a study examining the inhibition of orexin neurons (virus: AAV2-hSyn-DIO-hM4Di-mCherry), testing began 15 minutes prior to dark cycle onset. Clozapine n-oxide (CNO; 1 or 5 mg/kg) or saline was injected intraperitoneally and time spent moving in open field chambers was recorded for 2 h. Follow-up studies in separate mice cohorts quantified SPA in parallel with changes in energy expenditure (EE) and chow intake using indirect calorimetry chambers (SableSystem™). Following acclimation, testing sessions (saline and/or CNO) took place over the course of ~1 week, with injections administered every day. Changes in SPA, EE, chow intake, fecal boli, and body composition (EchoMRI™) were measured. Additional mice cohorts were fed a high-fat diet (HFD) and injected with CNO daily up to 10 days to assess the potential for orexin activation to prevent diet-induced obesity. Results Activation of orexin resulted in increases in SPA in male and female mice, and was accompanied by increases in energy expenditure without changes in overall chow intake. When orexin activation occurred in the context of high fat diet, weight gain and adiposity were significantly attenuated. SPA was decreased when DREADDs were used to inhibit orexin activity. Conclusion These results demonstrate that orexin neurons play a critical role in mediating physical activity and suggest a novel therapeutic target for treating obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuromodulation of orexin neurons reduces diet-induced adiposity

et al. 2017

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“…SPA was defined as the sum of time spent ambulatory and time spent moving in the vertical plane. Stereotypic activity was defined as time spent moving within a defined space around the animal (3.25 ϫ 3.25 inches), as measured by beam breaks (37).…”

Section: Spontaneous Physical Activity and Indirect Calorimetrymentioning

confidence: 99%

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

Noble

Billington

Kotz

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Noble EE, Billington CJ, Kotz CM, Wang C. Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure. Am J Physiol Regul Integr Comp Physiol 307: R737-R745, 2014. First published July 2, 2014; doi:10.1152/ajpregu.00118.2014.-Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin. oxytocin; ventromedial hypothalamus; energy expenditure; obesity; feeding OXYTOCIN HAS ANTIOBESITY EFFECTS and is currently being tested clinically for use in the treatment of obesity and Type 2 diabetes (34, 65). Although the mechanism for oxytocin's effects have not been fully characterized, an extensive body of work has demonstrated antiobesity effects of oxytocin in rodents (11,26,30,64,65), as well as humans (65). Behaviorally, central oxytocin has been reported to delay meal onset (2) and reduce intake of sweet foods (22,27,33). Additionally, previous studies implicate a physiological role for endogenous oxytocin in reducing meal size (7, 62). In addition to feeding effects, central oxytocin has potent effects on energy metabolism. For example, low doses of intracerebroventricular oxytocin promote weight loss in rats without affecting feeding by elevating fat oxidation in adipose tissue, whereas higher doses of intracerebroventricular oxytocin both reduce feeding and increase lipolysis (11). Conversely, animals deficient in either oxytocin or its receptor show reduced energy expenditure, in some cases with normal feeding (1, 9, 19, 51).The main sources of oxytocin in the brain are the magnocellular and par...

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Diversity of Thermogenic Capacity Predicts Divergent Obesity Susceptibility in a Wild Rodent

Zhang

Shen

Liu

et al. 2017

Obesity

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Objective: The objective of the present study was to examine whether wild rodents exhibit diverse obesity susceptibility and what factors predispose subjects to this divergence in response to a high-fat diet (HFD). Methods: Sixty male and female Brandt's voles (Lasiopodomys brandtii) were fed an HFD for 8 weeks, and the upper (obesity prone [OP]) and lower (obesity resistant [OR]) one-third for mass gain were selected. Energy budgets and pathologic changes were measured. Another 30 males were fed a low-fat control diet (LFD) for 10 weeks and then fed an HFD for 12 weeks. The energetic parameters of the rodents on an LFD were analyzed for the correlation with body mass of the rodents on an HFD. Results: OP voles had higher energy intakes, higher levels of noradrenaline-induced nonshivering thermogenesis, and a greater impairment of insulin tolerance than OR voles. Unlike laboratory rodents, there were no differences in physical activity or resting metabolic rate between these groups of voles. The thermogenic capacity during LFD feeding was the strongest predictor for mass gain during HFD feeding. Conclusions: This study suggests that a wild rodent species of Brandt's voles exhibits diverse obesity susceptibility in reaction to an HFD, providing a natural model to give insight into the mechanisms for divergent obesity susceptibility. This study also indicates that maximum thermogenic capacity has a predictive power for the development of obesity when an HFD was available.

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High and low activity rats: Elevated intrinsic physical activity drives resistance to diet‐induced obesity in non‐bred rats

Cited by 37 publications

References 38 publications

Neuromodulation of orexin neurons reduces diet-induced adiposity

Neuromodulation of orexin neurons reduces diet-induced adiposity

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

Diversity of Thermogenic Capacity Predicts Divergent Obesity Susceptibility in a Wild Rodent

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