The effect of orexin A on food intake and spontaneous physical activity in the paraventricular nucleus and ventral tegmental area

Appetite ◽  
2010 ◽  
Vol 54 (3) ◽  
pp. 641
Author(s):  
P. David ◽  
J.A. Teske ◽  
M.K. Grace ◽  
C.J. Billington ◽  
C.M. Kotz
2004 ◽  
Vol 286 (4) ◽  
pp. E551-E559 ◽  
Author(s):  
Kohji Kiwaki ◽  
Catherine M. Kotz ◽  
Chuanfeng Wang ◽  
Lorraine Lanningham-Foster ◽  
James A. Levine

In humans, nonexercise activity thermogenesis (NEAT) increases with positive energy balance. The mediator of the interaction between positive energy balance and physical activity is unknown. In this study, we address the hypothesis that orexin A acts in the hypothalamic paraventricular nucleus (PVN) to increase nonfeeding-associated physical activity. PVN-cannulated rats were injected with either orexin A or vehicle during the light and dark cycle. Spontaneous physical activity (SPA) was measured using arrays of infrared activity sensors and night vision videotaped recording (VTR). O2 consumption and CO2 production were measured by indirect calorimetry. Feeding behavior was assessed by VTR. Regardless of the time point of injection, orexin A (1 nmol) was associated with dramatic increases in SPA for 2 h after injection (orexin A: 6.27 ± 1.95 × 103 beam break count, n = 24; vehicle: 1.85 ± 1.13 × 103, n = 38). This increase in SPA was accompanied by compatible increase in O2 consumption. Duration of feeding was increased only when orexin A was injected in the early light phase and accounted for only 3.5 ± 2.5% of the increased physical activity. In a dose-response experiment, increases in SPA were correlated with dose of orexin A linearly up to 2 nmol. PVN injections of orexin receptor antagonist SB-334867 were associated with decreases in SPA and attenuated the effects of PVN-injected orexin A. Thus orexin A can act in PVN to increase nonfeeding-associated physical activity, suggesting that this neuropeptide might be a mediator of NEAT.


2016 ◽  
Vol 311 (3) ◽  
pp. R592-R599 ◽  
Author(s):  
Sarah J. Terrill ◽  
Kellie M. Hyde ◽  
Kristen E. Kay ◽  
Hayden E. Greene ◽  
Calyn B. Maske ◽  
...  

Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal.


2019 ◽  
Vol 31 (7) ◽  
Author(s):  
Sarah H. Lockie ◽  
Romana Stark ◽  
David C. Spanswick ◽  
Zane B. Andrews

2013 ◽  
Vol 38 (9) ◽  
pp. 1685-1697 ◽  
Author(s):  
Elizabeth G Mietlicki-Baase ◽  
Laura E Rupprecht ◽  
Diana R Olivos ◽  
Derek J Zimmer ◽  
Mark D Alter ◽  
...  

2000 ◽  
Vol 83 (S1) ◽  
pp. S17-S20 ◽  
Author(s):  
Eric Ravussin ◽  
Clifton Bogardus

The prevalence of obesity is reaching epidemic proportions in many industrialized countries. There is growing evidence that, even if the trigger of this epidemic is found in changes in the environment, genes are interacting with the environment to cause weight gain. Studies of twins reared apart indicate that approximately two-thirds of the variability in BMI is attributed to genetic factors. From prospective studies in Pima Indians we can ascribe 12 % of the variability in BMI to metabolic rate, 5 % to fat oxidation, and another probable 10 % to the level of spontaneous physical activity. These data indicate that at least 40 % of the variability in BMI is related to genetic factors involved in the regulation of food intake and/or volitional activity. This indicates that the most likely successful therapy for obesity may target pathways of the regulation of food intake. Similarly, an environment favouring engagement in physical activity should be promoted.


2009 ◽  
Vol 297 (1) ◽  
pp. R176-R184 ◽  
Author(s):  
J. A. Teske ◽  
C. M. Kotz

Caloric restriction (CR) and metabolic glucoprivation affect spontaneous physical activity (SPA), but it's unknown whether these treatments similarly affect SPA in selectively bred obesity-prone (OP) and -resistant (OR) rats. OR rats have greater basal SPA and are more responsive to treatments that modulate SPA, such as orexin A administration. We hypothesized that OR rats would be more sensitive to other treatments modulating SPA. To test this, continuous 24-h SPA was measured before and during acute (24 h) and chronic (8 wk) CR in OR, OP, and Sprague-Dawley rats. Pharmacological glucoprivation was produced by injection of 2-deoxyglucose (2-DG), and SPA was measured 5 h postinjection. Acute CR increased SPA in all groups; however, the effect was dependent on the index of SPA and time interval during the 24-h time period. In contrast to OR rats, chronic CR increased distance traveled, ambulatory episodes, and time spent in ambulation and stereotypy during the time interval preceding anticipation of food in OP and Sprague-Dawley rats. Although the effects of 2-DG treatment on SPA were minimal, OR rats had significantly greater SPA than OP and Sprague-Dawley rats independent of treatment. That chronic CR failed to result in significant changes in SPA in OR rats suggests that these rats may be especially unresponsive to treatments modulating feeding. This insensitivity coupled with elevated basal SPA levels may in part mediate phenotypic traits of lean rats.


2012 ◽  
Vol 303 (7) ◽  
pp. E865-E874 ◽  
Author(s):  
Claudio E. Perez-Leighton ◽  
Kelsey Boland ◽  
Jennifer A. Teske ◽  
Charles Billington ◽  
Catherine M. Kotz

There is significant variability in diet-induced obesity (DIO) among humans and rodents, which has been associated with differences in intrinsic spontaneous physical activity (SPA). The orexin neuropeptides positively modulate SPA through multiple brain sites, but the effects of DIO on orexin's activity are not well understood. In this study, we tested the hypothesis that DIO sensitivity is mediated by decreased SPA and changes in the function of the orexins. As a DIO model, we used male Sprague-Dawley rats fed a high-fat (HF; 45% kcal from fat) or a low-fat (LF; 10% kcal from fat) diet for 10 wk. We measured SPA before and after HF or LF feeding and expression of orexin receptors by real-time PCR after dietary treatments. We tested DIO effects on orexin signaling by measuring SPA after injection of orexin A in the rostral lateral hypothalamus (RLH) before and after 10 wk of HF feeding. Finally, we tested whether daily orexin A RLH injections prevent DIO caused by HF feeding. Our results show that resistance to DIO is associated with an increase in SPA, SPA after injection of orexin A in RLH, and orexin receptor expression in sites that mediate orexin's effect on SPA, including RLH. We show that daily injections of orexin peptide in RLH prevent DIO without altering food intake. We estimate that the energetic cost of SPA after orexin A RLH injection accounts for approximately 61% of the extra caloric intake associated with HF intake, suggesting additional effects of orexins. In summary, our results suggest that variability in DIO sensitivity is mediated through adaptations in the activity of the orexin peptides and their receptors.


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