Effect of acute and chronic caloric restriction and metabolic glucoprivation on spontaneous physical activity in obesity-prone and obesity-resistant rats

2009 ◽  
Vol 297 (1) ◽  
pp. R176-R184 ◽  
Author(s):  
J. A. Teske ◽  
C. M. Kotz
Keyword(s):  
Physical Activity ◽  
Caloric Restriction ◽  
Phenotypic Traits ◽  
Time Interval ◽  
Sprague Dawley ◽  
Orexin A ◽  
Time Period ◽  
Sprague Dawley Rats ◽  
Spontaneous Physical Activity

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.

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

2006 ◽  
Vol 291 (4) ◽  
pp. R889-R899 ◽  
Author(s):  
J. A. Teske ◽  
A. S. Levine ◽  
M. Kuskowski ◽  
J. A. Levine ◽  
C. M. Kotz
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Caloric Intake ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Orexin A ◽  
Daily Caloric Intake ◽  
Behavioral Studies ◽  
Sprague Dawley Rats ◽  
Spontaneous Physical Activity

Selectively-bred obesity-resistant [diet resistant (DR)] rats weigh less than obesity-prone [diet-induced obese (DIO)] rats, despite comparable daily caloric intake, suggesting phenotypic energy expenditure differences. Human data suggest that obesity is maintained by reduced ambulatory or spontaneous physical activity (SPA). The neuropeptide orexin A robustly stimulates SPA. We hypothesized that DR rats have greater: 1) basal SPA, 2) orexin A-induced SPA, and 3) preproorexin, orexin 1 and 2 receptor (OX1R and OX2R) mRNA, compared with DIO rats. A group of age-matched out-bred Sprague-Dawley rats were used as additional controls for the behavioral studies. DIO, DR, and Sprague-Dawley rats with dorsal-rostral lateral hypothalamic (rLHa) cannulas were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 μl). SPA and food intake were measured for 2 h after injection. Preproorexin, OX1R and OX2R mRNA in the rLHa, and whole hypothalamus were measured by real-time RT-PCR. Orexin A significantly stimulated feeding in all rats. Orexin A-induced SPA was significantly greater in DR and Sprague-Dawley rats than in DIO rats. Two-mo-old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-mo-old DR rats had elevated OX1R and OX2R mRNA compared with DIO rats, although this increase was significant for OX2R only at this age. Thus DR rats show elevated basal and orexin A-induced SPA associated with increased OX1R and OX2R gene expression, suggesting that differences in orexin A signaling through OX1R and OX2R may mediate DIO and DR phenotypes.

scholarly journals Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats

2013 ◽  
Vol 305 (11) ◽  
pp. R1337-R1345 ◽  
Author(s):  
Jennifer A. Teske ◽  
Claudio E. Perez-Leighton ◽  
Charles J. Billington ◽  
Catherine M. Kotz
Keyword(s):  
Physical Activity ◽  
Locus Coeruleus ◽  
Expression Pattern ◽  
Principal Component ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Orexin A ◽  
Orexin Receptors ◽  
Sprague Dawley Rats ◽  
Spontaneous Physical Activity

Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons that project to the prefrontral cortex, which may influence spontaneous physical activity (SPA) and energy balance. Obesity-resistant (OR) rats have higher orexin receptors (OXR) mRNA in the LC and other brain regions, as well as lower adiposity compared with obese rats. These findings led us to hypothesize that orexin activity in the LC is relevant for the OR phenotype. We compared OR rats to Sprague-Dawley rats. We predicted that: 1) brain OXR expression pattern is sufficient to differentiate OR from non-bred Sprague-Dawley rats; 2) nonresting energy expenditure (NREE) and orexin A (OXA)-stimulated SPA after injection in LC would be greater in OR rats; and 3) the effect of OXA on SPA would be greater than its effect on feeding. OXR mRNA from 11 brain sites and the SPA and feeding responses to OXA in the LC were determined. Body composition, basal SPA, and EE were determined. Principal component analysis of the OXR expression pattern differentiates OR and Sprague-Dawley rats and suggests the OXR mRNA in the LC is important in defining the OR phenotype. Compared with Sprague-Dawley rats, OR rats had greater SPA and NREE and lower resting EE and adiposity. SPA responsivity to OXA in the LC was greater in OR rats compared with Sprague-Dawley rats. OXA in the LC did not stimulate feeding in OR or Sprague-Dawley rats. These data suggest that the LC is a prominent site modulating OXA-stimulated SPA, which promotes lower adiposity and higher nonresting EE.

scholarly journals Behavioral responses to orexin, orexin receptor gene expression, and spontaneous physical activity contribute to individual sensitivity to obesity

2012 ◽  
Vol 303 (7) ◽  
pp. E865-E874 ◽  
Author(s):  
Claudio E. Perez-Leighton ◽  
Kelsey Boland ◽  
Jennifer A. Teske ◽  
Charles Billington ◽  
Catherine M. Kotz
Keyword(s):  
Physical Activity ◽  
Receptor Gene ◽  
Caloric Intake ◽  
Receptor Expression ◽  
Energetic Cost ◽  
Sprague Dawley ◽  
Orexin A ◽  
Orexin Receptors ◽  
Before And After ◽  
Spontaneous Physical Activity

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.

scholarly journals Chronic Nephropathy in Ad Libitum Overfed Sprague-Dawley Rats and Its Early Attenuation by Increasing Degrees of Dietary (Caloric) Restriction to Control Growth

2000 ◽  
Vol 28 (6) ◽  
pp. 788-798 ◽  
Author(s):  
Kevin P. Keenan ◽  
John B. Coleman ◽  
Carol L. Mccoy ◽  
Chao-Min Hoe ◽  
Keith A. Soper ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Sprague Dawley ◽  
Chronic Nephropathy ◽  
Sprague Dawley Rats ◽  
Control Growth ◽  
Ad Libitum

Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats

2004 ◽  
Vol 286 (4) ◽  
pp. E551-E559 ◽  
Author(s):  
Kohji Kiwaki ◽  
Catherine M. Kotz ◽  
Chuanfeng Wang ◽  
Lorraine Lanningham-Foster ◽  
James A. Levine
Keyword(s):  
Physical Activity ◽  
Energy Balance ◽  
Paraventricular Nucleus ◽  
Night Vision ◽  
Hypothalamic Paraventricular Nucleus ◽  
Positive Energy ◽  
Orexin A ◽  
Positive Energy Balance ◽  
Activity Sensors ◽  
Spontaneous Physical Activity

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.

Area postrema: essential for support of arterial pressure after hemorrhage in rats

1990 ◽  
Vol 258 (6) ◽  
pp. R1472-R1478 ◽  
Author(s):  
K. M. Skoog ◽  
M. L. Blair ◽  
C. D. Sladek ◽  
W. M. Williams ◽  
M. L. Mangiapane
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Data Acquisition ◽  
Area Postrema ◽  
Plasma Renin ◽  
Base Line ◽  
Sprague Dawley ◽  
Time Period ◽  
Sprague Dawley Rats

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.

scholarly journals Differential Effects of Long-Term Caloric Restriction and Dietary Protein Source on Bone and Marrow Fat of the Aging Rat

2020 ◽  
Vol 75 (11) ◽  
pp. 2031-2036 ◽  
Author(s):  
Gustavo Duque ◽  
Ahmed Al Saedi ◽  
Daniel Rivas ◽  
Stéphanie Miard ◽  
Guylaine Ferland ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Bone Quality ◽  
Tissue Expression ◽  
Sprague Dawley ◽  
Marrow Fat ◽  
Differential Effects ◽  
Sprague Dawley Rats ◽  
Negative Effect ◽  
Ad Libitum

Abstract Long-term caloric restriction (CR) has been shown to be beneficial to various tissues and organs. In contrast, CR exerts differential effects on bone, which could be due in part to the nature of the protein regime utilized. Male Sprague Dawley rats (8-month-old) were subjected for 12 months to 40% CR in macronutrients and compared with rats fed ad libitum for the same period. Casein- and soy-fed groups were compared. There was a significant decrease in bone quality in both CR groups, which was independent of the source of protein in the diet. In contrast, the group fed soy protein ad libitum showed better bone quality and higher levels of bone formation compared with casein-fed animals. Notably, bone marrow adipocytes were not mobilized upon CR as demonstrated by an absence of change in adipocyte number and tissue expression of leptin. This study demonstrates that the negative effect of CR on bone quality could not be prevented by the most common protein regimes.

Abstract 211: Delayed Cell Death in CA1 Region in a Cardiac Arrest Rat Model: Continuing After 2 Weeks of Survival?

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sandra Högler ◽  
Ursula Teubenbacher ◽  
Wolfgang Weihs ◽  
Fritz Sterz ◽  
Ingrid A M Magnet ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiac Arrest ◽  
Brain Regions ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Ca1 Region ◽  
Delayed Cell Death ◽  
Time Period ◽  
Sprague Dawley Rats ◽  
Hematoxylin Eosin

Background: Evolution of histological lesions in selectively vulnerable brain regions in animal models of cardiac arrest (CA)give evidence of potential therapeutic windows. Delayed cell death is of special interest in this regard. Methods: In male Sprague-Dawley rats (350g) ventricular fibrillation (VF) CA was induced for 6 min followed by chest compressions, ventilation and drugs for 2 min. To achieve return of spontaneous circulation animals were defibrillated every 2 min. Animals were sacrificed after one week (n=5) or two weeks (n=7) of survival and compared to four sham animals. Brains were fixed in formalin, embedded in paraffin wax and cut into 3 μm thick coronary sections for histological examination. Viable neurons with nucleolus were counted in Hematoxylin-Eosin (HE)-stained sections in a 250 μm sector of the medial CA1 region. FluoroJade B staining was applied to count dying neurons in the same sector. Results: In HE-staining sham animals had 31±4 viable neurons. In one week survivors 11±9 viable neurons (p=0.003) and in two week survivors 7±7 viable neurons (p=0.001 vs sham, p=0.49 vs one week survivors) were counted. Furthermore, a lot of degenerated hypereosinophilic neurons were present in HE-staining in both CA-groups. FluoroJade B-staining was negative in sham animals. In one week survivors 29±8 dying neurons (p=0.006) and in two week survivors 33±13 dying neurons (p= 0.016 vs sham, p=0.343 vs one week survivors) were detectable. Conclusions: Consistent damage in the medial CA1 region was present after 6 min VFCA in both survival time groups. Lesions seemed to be constant, with no significant differences between time points. Contrary to expectations, FluoroJade B-staining was still positive after two weeks of survival, suggesting that delayed cell death might go on for a longer time period than assumed so far.

Regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation

2003 ◽  
Vol 284 (6) ◽  
pp. R1409-R1417 ◽  
Author(s):  
Andrew J. Thorpe ◽  
Mary A. Mullett ◽  
Chuanfeng Wang ◽  
Catherine M. Kotz
Keyword(s):  
Metabolic Status ◽  
Dependent Manner ◽  
Feeding Response ◽  
Sprague Dawley ◽  
Neural Structure ◽  
Orexin A ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid ◽  
Efferent Projections ◽  
Rostral Region

Orexin A (OX-A) administered in the lateral hypothalamus (LH) increases feeding in a dose-dependent manner. The LH is a relatively large neural structure with a heterogeneous profile of neural inputs, efferent projections, and orexin receptor distribution. We sought to determine the LH region most sensitive to the feeding stimulatory effect of OX-A injection. Fifty-six male Sprague-Dawley rats were fitted with cannulas 1 mm above four separate LH regions ∼1 mm apart in the rostral-caudal direction. There were 14–16 animals/LH region. After recovery, animals received either artificial cerebrospinal fluid or OX-A (250, 500, or 1,000 pmol). To determine whether there is a circadian effect of LH OX-A on the feeding response, we performed injections at 0200, 0900, 1400, and 2100. Food intake was measured at 1, 2, and 4 h after injection. The most rostral extent of the LH was the only region in which injection of OX-A significantly stimulated feeding. Within this region, feeding was increased at all times of the day, although the most robust and only significant feeding response occurred after the afternoon injection (1400) of OX-A. To determine the extent to which the metabolic status of the rat contributed to the circadian specificity of orexin-induced feeding, animals were placed on a restricted diet and injected with OX-A in the most rostral region of the LH. Under these conditions, OX-A significantly increased feeding and more robustly when compared with animals on a nonrestricted diet. These data suggest that the rostral LH is the only region of the LH sensitive to the injection of OX-A, and the metabolic status of the animal at the time of injection may influence the feeding response to OX-A.

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