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

Teske, Jennifer A.; Levine, Allen S.; Kuskowski, Michael A.; Levine, James A.; Kotz, Catherine M.

doi:10.1152/ajpregu.00536.2005

Cited by 100 publications

(156 citation statements)

References 56 publications

(74 reference statements)

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“…These data are consistent with the observation of greater SPA and NEAT in adult lean humans [9]. In addition, elevated SPA in 1- to 2-month-old OR rats [35] and higher resting energy expenditure in 10-year-old lean children [259] indicate that differences between SPA and energy expenditure between the lean and obese present early in life and track throughout adulthood. Together these data support the idea that elevated SPA and energy expenditure may confer obesity resistance in rats and humans.…”

Section: Role Of Neat In Obesity Resistancesupporting

confidence: 86%

“…Specific mechanisms modulating energy expenditure and conferring obesity resistance to OR rats and perpetuating obesity in OP rats are currently under investigation. We showed that relative to OP and Sprague-Dawley rats, OR rats were significantly more responsive to the SPA-promoting effects of orexin-A [21, 35]. The mechanism mediating this increased sensitivity to orexin-A in OR rats is not yet defined, but we showed that OR rats had significantly greater orexin receptor gene expression relative to OP rats.…”

Section: Role Of Neat In Obesity Resistancementioning

confidence: 76%

“…Rats selectively bred for their resistance to obesity display greater SPA when compared to obesity-prone (OP) rats, independent of age or body weight [35], suggesting that level of NEAT is inherent and protects against obesity. This finding parallels human studies suggesting that high levels of basal NEAT offset increases in caloric intake [9, 21].…”

Section: Physiological Significance Of Spa and Neat To Energy Balancementioning

confidence: 99%

“…Orexin-A infusion into the lateral, third or fourth ventricle [168,169,170] in addition to the LC [171], rostral LH [35, 172], PVN [15, 21], shell of the NAcc [173], SN [174], and VTA [175] increased SPA in a dose-dependent manner. In addition, we observed increased SPA following orexin-A infusion into the TMN and dorsal raphe (DR), which are both part of the ascending cortical arousal pathway [176].…”

Section: Potential Mediators Of Neatmentioning

confidence: 99%

“…Unlike out-bred OP rats, which gained weight readily, out-bred OR rats maintained body weight gain similar to non-high-fat-fed Sprague-Dawley rats. Subsequently, a selective breeding scheme (obese males mated with obese females and lean males mated with lean females) for over 10 years has generated OP and OR rats with divergent body weight gain patterns despite similar caloric intake on a chow diet [35, 257, 258], which suggests that phenotypic differences in body weight gain are due to differences in energy expenditure. OR rats display greater basal SPA and energy expenditure [kcal/(g body weight) 0.75 ] over 24 h as compared to OP rats despite greater caloric intake [unpublished data and [35]].…”

Section: Role Of Neat In Obesity Resistancementioning

confidence: 99%

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Neuropeptidergic Mediators of Spontaneous Physical Activity and Non-Exercise Activity Thermogenesis

Teske¹,

Billington

Kotz³

2007

Neuroendocrinology

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Lean individuals have high levels of spontaneous physical activity (SPA) and the energy expenditure derived from that activity, termed non-exercise activity thermogenesis or NEAT, appears to protect them from obesity. Conversely, obesity in different human populations is characterized by low levels of SPA and NEAT. Like in humans, elevated SPA in rats appears to protect against obesity: obesity-resistant rats have significantly greater SPA and NEAT than obesity-prone rats. We review the literature on brain mechanisms important in mediating SPA and NEAT. The focus is on neuropeptides, including cholecystokinin, corticotropin-releasing hormone (also known as corticotropin-releasing factor), neuromedin U, neuropeptide Y, leptin, agouti-related protein, orexin-A (also known as hypocretin-1), and ghrelin. We also review information regarding interactions between these neuropeptides and dopamine, a neurotransmitter important in mediating motor function. Finally, we present evidence that elevated signaling of pathways mediating SPA and NEAT may protect against weight gain and obesity.

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Section: Role Of Neat In Obesity Resistancesupporting

confidence: 86%

Section: Role Of Neat In Obesity Resistancementioning

confidence: 76%

Section: Physiological Significance Of Spa and Neat To Energy Balancementioning

confidence: 99%

Section: Potential Mediators Of Neatmentioning

confidence: 99%

Section: Role Of Neat In Obesity Resistancementioning

confidence: 99%

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Neuropeptidergic Mediators of Spontaneous Physical Activity and Non-Exercise Activity Thermogenesis

Teske¹,

Billington

Kotz³

2007

Neuroendocrinology

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An anatomically distinct subpopulation of orexin neurons project from the lateral hypothalamus to the olfactory bulb

Fadool

Storace

2023

J of Comparative Neurology

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Olfactory cues play a key role in natural behaviors such as finding food, finding mates, and avoiding predators. In principle, the ability of the olfactory system to carry out these perceptual functions would be facilitated by signaling related to an organism's physiological state. One candidate pathway includes a direct projection from the hypothalamus to the main olfactory bulb, the first stage of olfactory sensory processing. The pathway from the hypothalamus to the main olfactory bulb is thought to include neurons that express the neuropeptide orexin, although the proportion that is orexinergic remains unknown. A current model proposes that the orexin population is heterogeneous, yet it remains unknown whether the proportion that innervates the main olfactory bulb reflects a distinct subpopulation of the orexin population. Herein, we carried out combined retrograde tract tracing with immunohistochemistry for orexin‐A in the mouse to define the proportion of hypothalamic input to the main olfactory bulb that is orexinergic and to determine what fraction of the orexin‐A population innervates the bulb. The numbers and spatial positions of all retrogradely labeled neurons and all the orexin‐A‐expressing neurons were quantified in sequential sections through the hypothalamus. Retrogradely labeled neurons were found in the ipsilateral hypothalamus, of which 22% expressed orexin‐A. The retrogradely labeled neurons that did and did not express orexin‐A could be anatomically distinguished based on their spatial position and cell body area. Remarkably, only 7% of all the orexin‐A neurons were retrogradely labeled, suggesting that only a small fraction of the orexin‐A population directly innervate the main olfactory bulb. These neurons spatially overlapped with the orexin‐A neurons that did not innervate the bulb, although the two cell populations were differentiated based on cell body area. Overall, these results support a model in which olfactory sensory processing is influenced by orexinergic feedback at the first synapse in the olfactory processing pathway.

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Changes in sensorimotor cortex oscillatory activity by orexin‐A in the ventrolateral preoptic area of the hypothalamus reflect increased muscle tone

Mavanji

Teske

Kotz

et al. 2023

J of Neuroscience Research

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Orexin-A (OXA) is a hypothalamic neuropeptide implicated in the regulation of wakefulness, appetite, reward processing, muscle tone, motor activity, and other physiological processes. The broad range of systems affected stems from the widespread projections of orexin neurons toward multiple brain regions regulating numerous physiological processes. Orexin neurons integrate nutritional, energetic, and behavioral cues and modulate the functions of target structures. Orexin promotes spontaneous physical activity (SPA), and we recently showed that orexin injected into the ventrolateral preoptic area (VLPO) of the hypothalamus increases behavioral arousal and SPA in rats. However, the specific mechanisms underlying the role of orexin in physical activity are unknown. Here we tested the hypothesis that OXA injected into the VLPO alters the oscillatory activity in the electroencephalogram (EEG) to reflect an increased excitability of the sensorimotor cortex, which may explain the associated increase in SPA. The results showed that OXA increased wakefulness following injections into the VLPO. In addition, OXA altered the power spectrum of the EEG during the awake state by decreasing the power of 5-19 Hz oscillations and increasing the power of >35 Hz oscillations, which are markers of increased sensorimotor excitability. Consistently, we found that OXA induced greater muscle activity. Furthermore, we found a similar change in power spectrum during slow-wave sleep, which suggests that OXA altered the EEG activity in a fundamental way, even in the absence of physical activity. These results support the idea that OXA increases the excitability of the sensorimotor system, which may explain the corresponding increase in awake time, muscle tone, and SPA.

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

Cited by 100 publications

References 56 publications

Neuropeptidergic Mediators of Spontaneous Physical Activity and Non-Exercise Activity Thermogenesis

Neuropeptidergic Mediators of Spontaneous Physical Activity and Non-Exercise Activity Thermogenesis

An anatomically distinct subpopulation of orexin neurons project from the lateral hypothalamus to the olfactory bulb

Changes in sensorimotor cortex oscillatory activity by orexin‐A in the ventrolateral preoptic area of the hypothalamus reflect increased muscle tone

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