Elevated hypothalamic orexin signaling, sensitivity to orexin A and spontaneous physical activity in obesity resistant rats

Teske, Jennifer A.; Margosian, Mark R.; Kuskowski, Michael A.; Levine, James A.; Kotz, Catherine M.

doi:10.1016/j.yfrne.2006.03.214

Cited by 25 publications

(70 citation statements)

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“…Reductions in physical activity and NEAT are associated with weight gain and obesity in both rats [71,87] and humans [61,62]. To investigate how NEAT changes with increasing obesity, we examined potential brain mechanisms that modulate physical activity and energy expenditure.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that sensitivity of the PVN to the locomotor-activating effects of orexin decreases with obesity in rats [72]. Here, we examined NMU, a neuropeptide that modulates physical activity through its actions on brain regions that integrate signals relating to energy balance and body weight [40,42,48,71,73,85,87]. Because NMU affects energy balance through changes in both energy intake [24,25,34,37,44,69,96] and expenditure [17,[23][24][25]88,96], in part through increases in physical activity [24,69,73], we examined how NMU affects physical activity in obese and non-obese rats.…”

Section: Discussionmentioning

confidence: 99%

“…The strains of rats differ in body weight on a standard diet; the DIO rats increase their body weight on a high-energy diet whereas DR rats on the same diet do not differ in body weight from chow-fed control DR rats (unpublished data) [53]. In fact, it may be the DR rats, rather than the DIO rats, which are unusual in that their spontaneous activity is high and their body weight low compared to both DIO and control Sprague-Dawley rats [87]. The causes of the disparity in body weight between DIO and DR rats are multifaceted and polygenic, and physiological changes can be seen in the DIO rats before they develop obesity, including decreases in insulin and leptin sensitivities [54,57,89].…”

Section: Introductionmentioning

confidence: 95%

“…Others and we have demonstrated that the ability of orexin to increase physical activity and energy expenditure is enhanced in lean compared to obese rats [72,87]. First, we tested the hypothesis that the ability of NMU to increase physical activity and energy expenditure is decreased in obesity-prone DIO rats compared to lean DR rats.…”

Section: Introductionmentioning

confidence: 95%

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Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity

2007

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Obesity is associated with a decrease in energy expenditure relative to energy intake. The decrease in physical activity associated with obesity in several species, including humans, contributes to decreased energy expenditure. Several hormones and neuropeptides that affect appetite also modulate physical activity, including neuromedin U (NMU), a peptide found in the gut and brain. We have demonstrated that NMU microinjected into the hypothalamic paraventricular nucleus (PVN) in rats increases the energy expenditure associated with physical activity, called non-exercise activity thermogenesis (NEAT). Here we examined whether obesity in rats is related to decreased sensitivity of the PVN to the locomotor-activating effect of NMU. Diet-induced obese (DIO) rats and lean, dietresistant (DR) rats were given PVN microinjections of increasing doses of NMU both before and after one month on a high-fat diet. We found that NMU increases physical activity, energy expenditure, and NEAT in a dose-dependent manner in both DR and DIO rats, both before and after one month on the high-fat diet. Before high-fat feeding, the obesity-prone and lean rats showed similar levels of physical activity after intra-PVN microinjections of NMU. After one month of the high-fat diet, however, the obesity-resistant rats showed significantly more NMU-induced physical activity compared to the obese DIO rats. Taken together with previous studies, these results suggest that obesity may represent a state associated with decreased central sensitivity to neuropeptides such as NMU that increase physical activity and therefore energy expenditure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity

2007

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“…For example, the orexin level show no change [15,16] or a slight increase [17] after a HFD for 2-3 weeks, whereas the orexin level decrease after a HFD for 50 days [18]. In addition, the orexin 1r and 2r mRNA levels are found to be elevated in obesity-resistant rats [19]. Overall, these results suggest that changes in the orexin levels and their receptor expression may be related to the sleep/wakefulness abnormalities observed in HFD-induced obese mice.…”

Section: Introductionmentioning

confidence: 99%

Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid eye movement sleep level in high-fat diet-induced obese mice

Tanno

Terao

Okamatsu‐Ogura

et al. 2013

Obesity Research & Clinical Practice

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Orexins are hypothalamic neuropeptides, which play important roles in the regulation and maintenance of sleep/wakefulness states and energy homeostasis. To evaluate whether alterations in orexin system is associated with the sleep/wakefulness abnormalities observed in obesity, we examined the mRNA expression of prepro-orexin, orexin receptor type 1, (orexin 1r), and orexin receptor type 2 (oxexin 2r) in the hypothalamus in mice fed with a normal diet (ND) and high-fat diet (HFD)-induced obese mice. We also compared their relationships with sleep/wakefulness. Twenty-four, 4-week-old, male C57BL/6J mice were divided randomly into 3 groups, which received the following: (1) ND for 17 weeks; (2) HFD for 17 weeks; and (3) ND for 7 weeks and HFD for a further 10 weeks. The body weights of mice fed the HFD for 10-17 weeks were 112-150% of the average body weight of the ND group. The daily amount of non-rapid eye movement (NREM) sleep increased significantly in HFD-fed mice. These changes were accompanied by increases in the number but decreases in the duration of each NREM sleep episode. In addition, brief awakenings (<20 s epoch) during NREM sleep was nearly 2-fold more frequent. The mRNA level of prepro-orexin in the hypothalamus was significantly reduced in HFD-induced obese 3 mice, whereas the levels of orexin 1r and orexin 2r were unaffected. The daily amount of NREM sleep was negatively correlated with the hypothalamic prepro-orexin mRNA level, so these results suggest that the increased NREM sleep levels in HFD-induced obese mice are attributable to impaired orexin activity.

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

Perez‐Leighton¹,

Boland

Billington

et al. 2013

Obesity

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Humans and rodents show large variability in their individual sensitivity to diet-induced obesity, which has been associated with differences in intrinsic spontaneous physical activity (SPA). Evidence from genetic and out-bred rat obesity models shows that higher activity of the orexin peptides results in higher intrinsic SPA and protection against diet-induced obesity. Based on this, we hypothesized that naturally occurring variation in SPA and orexin signaling activity is sufficient to drive differences in sensitivity to diet-induced obesity. We analyzed orexin activity and sensitivity to diet-induced obesity in non-manipulated male Sprague Dawley rats selected for high and low intrinsic SPA. Our results defined a new model of differential DIO sensitivity, the high-activity and low activity-rats, and suggest that naturally occurring variations in intrinsic SPA cause differences in energy expenditure that are mediated by orexin signaling and alter DIO sensitivity.

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Elevated hypothalamic orexin signaling, sensitivity to orexin A and spontaneous physical activity in obesity resistant rats

Cited by 25 publications

References 0 publications

Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity

Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity

Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid eye movement sleep level in high-fat diet-induced obese mice

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

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