GLP-2 decreases food intake in the dorsomedial hypothalamic nucleus (DMH) through Exendin (9–39) in male Sprague-Dawley (SD) rats

Intracerebroventricular insulin decreases food intake (FI) . The central bed nucleus of the amygdala (CeA), as other regions of the brain regulating feeding behavior, expresses insulin receptors. Our objectives were to show an insulin anorectic response in the amygdala, study the effect of high-fat diets on this response, and map the neural network activated by CeA insulin using c-Fos immunohistochemistry. Sprague-Dawley (SD) rats fitted with unilateral CeA cannulas were adapted to a low-fat (LFD) diet before they were fed a high-fat diet (HFD). Their feeding response to CeA saline or insulin (8 mU) was tested after 24 h, 72 h, or 7 days of being on a HFD. In a second experiment, SD rats were fed the HFD for 3, 7, or 49 days and were then refed with the LFD. They were tested for their insulin response before and after an HFD and every 3 days for the following weeks. Insulin tolerance tests were performed in a parallel group of rats. The CeA insulin stimulation c-Fos expression was studied to identify the distribution of activated neuronal populations. Feeding an HFD for 72 h or more induced a CeA, but not peripheral, insulin resistance, which was slowly reversed by LFD refeeding. The duration of HFD feeding determined the time frame for reversal of the insulin resistance. CeA insulin increased c-Fos in multiple brain regions, including the arcuate nucleus/paraventricular nucleus region of the hypothalamus. We conclude that the amygdala may be an important site for insulin regulation of food intake and may have a significant role in determining susceptibility to HFD-induced obesity.

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The Dorsomedial Hypothalamic Nucleus In Autonomic And Neuroendocrine Homeostasis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100019971 ◽

1975 ◽

Vol 2 (1) ◽

pp. 45-60 ◽

Cited By ~ 44

Author(s):

Lee L. Bernardis

Keyword(s):

Growth Hormone ◽

Electrical Stimulation ◽

Food Intake ◽

Present Report ◽

Hypothalamic Nucleus ◽

Control Mechanisms ◽

Storage Site ◽

Dorsomedial Hypothalamic Nucleus ◽

Cervical Stimulation ◽

Stimulation Of

SUMMARY:Median eminence and ventromedial hypothalamus have in the past been the principal foci of research in neuroendocrine and neurovisceral control mechanisms. The present report provides an overview of work involving the dorsomedial hypothalamic nucleus (DMN). This structure is located dorsal to the ventromedial hypothalamic nucleus (VMN) and extends anteroposteriorly from the plane of the largest cross section of the VMN to the plane of the dorsal premammillary nucleus. Fibers from the DMN pass with the periventricular system and the dorsal longitudinal fasciculus of Schütz and have been traced to the midbrain tegmentum and reticular formation. Intrahypothalamic connections involve intensive networks between DMN, lateral hypothalamic nucleus (LHN) and VMN. Regarding neurotransmitters, recent studies indicate that the DMN receives noradrenergic innervation along two pathways, a dorsal and a ventral one. Monoamine-containing systems approach the DMN from the lateral hypothalamus and the bulk of these fibers are carried in the medium forebrain bundle from their cells of origin in the brain stem. Studies of the vascular supply indicate that both VMN and DMN receive their blood supply from the internal carotid artery. It has been recently demonstrated that the DMN is involved in the control of food intake and possibly water intake as well. Discrete lesions in the DMN have caused hypophagia and hypodipsia, and implantation of epinephrine and norepinephrine in this area has initiated eating. Many years ago, electrical stimulation of this area was reported to cause eating. Although DMN lesions cause hypodipsia, they do not result in the reduced water/food intake ratios that are so characteristic of the VMN syndrome. DMN lesions are also followed by reduced spontaneous activity (running wheel), but this reduced activity is not accompanied by increased weight gain and accretion of adipose tissue, the latter being consistently observed in the VMN rat. Rather, carcass fat remains normal in the DMN rat and carcass protein is either normal or slightly increased. Many of the aforementioned changes in weanling rats with DMN lesions, however, are not matched by similar alterations in the intermediary metabolism of carbohydrate and lipid. Possibly this is due to a “resetting” of a central autonomic control system that makes it possible for the DMN rat to adapt more efficiently to a reduced influx of substrate, i.e. the consistent hypophagia. From a review of the literature it appears that the DMN and their circuitry are involved in only a few neuroendocrine, i.e. hypothalamohypophyseal control mechanisms. Both lesion and cervical stimulation experiments suggest an involvement of the DMN in the control of LTH. Circumstantial evidence points to the DMN as a possible formation and/or storage site of growth hormone inhibiting factor (GIF). Although DMN rats show reduced ponderal and linear growth, they have been found to have normal or elevated plasma growth hormone (GH) levels. Both lesion and stimulation studies have yielded the impression that the DMN is not involved in thyroid, i.e., thyrotropin stimulating hormone releasing factor (TSHRF) control. Electrical stimulation of the DMN has been reported to result in a positive correlation between adrenal blood flow and adrenal corticoid release in hypophysectomized dogs. This has been interpreted as a coordinated response at the level of a “dorsomedial sympathetic vasodilator relay” rather than a “true” neuroendocrine effect via corticotropin releasing factor (CRF). Experiments that failed to demonstrate a relationship between the DMN and the tonic and cyclic control of luteinizing hormone releasing factor (LHRF) are discussed. The data reviewed indicate the existence in the dorsomedial hypothalamus of an area that exerts a profound influence on many aspects of neurovisceral and some neuroendocrine control systems.

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Feeding responses of rats with dorsomedial hypothalamic lesions given ip 2DG or glucose

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1978.235.3.r168 ◽

1978 ◽

Vol 235 (3) ◽

pp. R168-R174

Author(s):

L. L. Bellinger ◽

L. L. Bernardis ◽

S. Brooks

Keyword(s):

Food Intake ◽

Feeding Behavior ◽

Food Consumption ◽

The Other ◽

Hypothalamic Nucleus ◽

Saline Control ◽

Other Hand ◽

Dorsomedial Hypothalamic Nucleus ◽

Pass Through ◽

Bilateral Lesions

The glucoprivation effects of 2-deoxy-D-glucose (2DG) on feeding behavior were studied in rats with bilateral lesions of the dorsomedial hypothalamic nucleus (DMN) and sham-operated controls. The lesioned and sham-operated rats were injected intraperitoneally with 2DG (5% wt/vol) at doses of either 150 mg/kg, 300 mg/kg, or 500 mg/kg, or with saline ("control days"). At all doses significantly more sham-operated rats ate and showed an increased food consumption during the first few hours after 2DG injection when compared to saline control days. However, their 24-h food consumption was normal or less than normal, depending on the dose of 2DG. On the other hand, rats with DMN lesions (DMN-L) did not increase their food consumption during the 4 h after the injection at any of the 2DG doses. In a second experiment DMN-L and sham-operated controls were injected intraperitoneally with glucose (1.36 g/kg body wt or 2.72 g/kg body wt) or saline after an overnight fast. Glucose loads, compared to saline injections, significantly depressed the controls' food consumption only during the first hour of refeeding. On the other hand, glucose injections did not depress food intake of the DMN-L rats. It is suggested that DMN lesions may have either destroyed glucoreceptors in the DMN that monitor glucose or the glucoprivation effects caused by 2DG and/or glucoreceptive pathways that pass through the DMN.

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PRL-Releasing Peptide Inhibits Food Intake in Male Rats via the Dorsomedial Hypothalamic Nucleus and not the Paraventricular Hypothalamic Nucleus

Endocrinology ◽

10.1210/endo.142.10.8419 ◽

2001 ◽

Vol 142 (10) ◽

pp. 4236-4243 ◽

Cited By ~ 37

Author(s):

Leighton J. Seal ◽

Caroline J. Small ◽

Waljit S. Dhillo ◽

Sarah A. Stanley ◽

Caroline R. Abbott ◽

...

Keyword(s):

Food Intake ◽

Male Rats ◽

Hypothalamic Nucleus ◽

Paraventricular Hypothalamic Nucleus ◽

Dorsomedial Hypothalamic Nucleus

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Long-Evans and Sprague-Dawley rats exhibit divergent responses to refeeding after caloric restriction

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00602.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. R1468-R1476 ◽

Cited By ~ 32

Author(s):

S. A. Evans ◽

M. M. Messina ◽

W. D. Knight ◽

A. D. Parsons ◽

J. M. Overton

Keyword(s):

Food Intake ◽

Caloric Restriction ◽

Sprague Dawley ◽

Sd Rats ◽

Sprague Dawley Rats ◽

Complete Restoration ◽

Ad Libitum ◽

Long Evans ◽

Strain Dependent ◽

Stimulation Of

Mature male Sprague-Dawley (SD) and Long-Evans (LE) rats were instrumented with telemetry transmitters for measurement of heart rate (HR) and housed in room calorimeters for assessment of food intake and oxygen consumption (V̇o2) at standard laboratory temperatures (23°C) to examine physiological responses to caloric restriction (CR; 60% of baseline ad libitum calories for 2 wk) and refeeding. Ad libitum controls had stable food intake (84–88 kcal/day) and gained weight at rates of 3–4 g/day. Groups from both strains assigned to CR exhibited similar patterns of weight loss and reductions in V̇o2 and HR. Upon refeeding, SD rats exhibited a mild, transient hyperphagic response (1 day) accompanied by sustained suppression of V̇o2 and HR that remained evident 8 days after refeeding. In contrast, LE rats exhibited sustained daily hyperphagia that persisted 8 days after refeeding and was accompanied by a complete restoration of HR and V̇o2. The lower HR and V̇o2 observed during refeeding in SD rats were not due to reduced locomotor activity. The results reveal a strain-dependent divergent response to recovery from CR. We conclude that during recovery from CR, homeostatic stimulation of appetite or suppression of energy expenditure may occur selectively to restore body weight.

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Ingestive behavior of rats with ibotenic acid lesions of the dorsomedial hypothalamus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.5.r938 ◽

1987 ◽

Vol 252 (5) ◽

pp. R938-R946 ◽

Cited By ~ 2

Author(s):

L. L. Bellinger

Keyword(s):

Food Intake ◽

Ibotenic Acid ◽

Ingestive Behavior ◽

Hypothalamic Nucleus ◽

Sprague Dawley ◽

Dorsomedial Hypothalamus ◽

Reduced Body ◽

Sprague Dawley Rats ◽

Obesity Index ◽

Food And Water Intake

Rats with electrolytic or kainic acid (KA) lesions of the dorsomedial hypothalamic nucleus area (DMHA-L) are hypophagic, hypodipsic, and have a reduced body weight (BW) compared with controls. In the present study, male Sprague-Dawley rats received bilateral ibotenic acid (IBO) lesions of the DMHA (3 micrograms in 0.3 microliter) or sham (S) operations. During the next 32 days the IBO DMHA-L rats showed reduced (P less than 0.01) food and water intake, BW, and linear growth (P less than 0.03), although having a normal Lee obesity index. After a 24-h fast both groups became hyperphagic (P less than 0.01) with the DMHA-L group eating the most (P less than 0.01) during the 1st h; lost BW was regained at the same rate. In the absence of food, DMHA-L rats took less (P less than 0.01) water (data normalized) than S rats. During 24 h of water deprivation, both groups ate similar amounts of food (data normalized); following deprivation the groups were hyperdipsic. Both groups increased their food intake when given 300 mg/kg of 2-deoxy-D-glucose, which contrasts rats with electrolytic or KA DMHA-L rats. Both groups decreased their food intake when given cholecystokinin (3 micrograms/kg ip), which contrasts rats with electrolytic DMHA-L. The DMHA-L rats were not deficient in plasma glucose, insulin, growth hormone, or plasma Na+ and K+. Histology revealed many, but not all neurons, were destroyed in the DMN after IBO. The data indicate that IBO, electrolytic, or KA lesions of the DMHA produce similar but not identical physiological changes.

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Deep brain stimulation for treatment of obesity in rats

Journal of Neurosurgery ◽

10.3171/jns-07/10/0809 ◽

2007 ◽

Vol 107 (4) ◽

pp. 809-813 ◽

Cited By ~ 65

Author(s):

Sepehr Sani ◽

Kirk Jobe ◽

Adam Smith ◽

Jeffrey H. Kordower ◽

Roy A. E. Bakay

Keyword(s):

Weight Loss ◽

Weight Gain ◽

Deep Brain Stimulation ◽

Food Intake ◽

Brain Stimulation ◽

Hypothalamic Nucleus ◽

Control Group ◽

Sprague Dawley ◽

Treatment Of Obesity ◽

Deep Brain

Object Given the success of deep brain stimulation (DBS) in a variety of applications (for example, Parkinson disease and essential tremor), other indications for which there is currently little effective therapy are being evaluated for clinical use of DBS. Obesity may be one such indication. Studies of the control of feeding and appetite by neurosurgical lesioning have been completed previously. This study was conducted to test the authors' hypothesis that continuous bilateral stimulatory inhibition of the rat lateral hypothalamic nucleus (LH) would lead to significant and sustained decrease in food intake and subsequent weight loss. Methods Sixteen Sprague–Dawley rats were maintained on a high-fat diet. Daily food intake and weight gain were measured for 7 days, at which time the animals underwent stereotactic placement of 0.25-mm-diameter bipolar stimulating electrodes bilaterally in the LH. On postoperative Day 7, eight animals began to receive continuous stimulation of the LH. The remaining eight animals were left unstimulated as the control group. Individual animal weight, food intake, and water intake were monitored daily and continuously throughout the experiment until postoperative Day 24. Results There was a decreased rate of weight gain after surgery in all animals, but the unstimulated group recovered and resumed a linear weight gain curve. The stimulated group, however, failed to show weight gain and remained below the mean baseline for body mass. There was a significant weight loss between the stimulated and unstimulated groups. On postoperative Day 24, compared with the day of surgery (Day 0), the unstimulated group had a mean weight gain of 13.8%, whereas the stimulated group had a 2.3% weight loss on average (p = 0.001), yielding a 16.1% weight difference between the two groups. Conclusions Bilateral electrical stimulatory inhibition of the LH is effective in causing significant and sustained weight loss in rats.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00118.2014 ◽

2014 ◽

Vol 307 (6) ◽

pp. R737-R745 ◽

Cited By ~ 43

Author(s):

Emily E. Noble ◽

Charles J. Billington ◽

Catherine M. Kotz ◽

ChuanFeng Wang

Keyword(s):

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Taste Aversion ◽

Conditioned Taste Aversion ◽

Negative Regulator ◽

Hypothalamic Nucleus ◽

Sprague Dawley ◽

Ventromedial Hypothalamic Nucleus ◽

Oxytocin Receptors

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.

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Differences in brown adipose tissue thermogenic responses between Long-Evans and Sprague-Dawley rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.1.r59 ◽

1992 ◽

Vol 263 (1) ◽

pp. R59-R69

Author(s):

J. Thornhill ◽

I. Halvorson

Keyword(s):

Adipose Tissue ◽

Electrical Stimulation ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Hypothalamic Nucleus ◽

Sprague Dawley ◽

Sd Rats ◽

Brown Adipose ◽

Long Evans ◽

Thermogenic Capacity

Temperature experiments of 4- and 21 degrees C-acclimated conscious and anesthetized Sprague-Dawley (SD) and Long-Evans (LE) rats revealed that the LE groups or SD rats acclimated to 4 degrees C had significant increases in intracapsular brown adipose tissue (IBAT) temperature above core after ventromedial hypothalamic nucleus (VMH) electrical stimulation or after norepinephrine (NE) infusion (50 micrograms/kg total dose), whereas IBAT temperatures of SD rats (acclimated to 21 degrees C) rose only after intravenous NE. Another study of 21- or 4 degrees C-acclimated SD rats revealed that only the 4 degrees C-acclimated group showed graded increases in IBAT temperature after VMH electrical stimulation as current amplitude or total current duration (not pulse frequency) of the electrical stimulus was increased. In vitro analysis of isolated IBAT tissues of age-matched anesthetized LE or SD rats acclimated to 21 degrees C showed that many indicators of thermogenic capacity including mitochondrial uncoupling protein were significantly lower in the SD group. The results demonstrate that lean male SD rats acclimated to 21 degrees C have suppressed IBAT temperature responses to VMH electrical stimulation compared with lean LE rats due to a reduced thermogenic capacity of that tissue.

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