Reduced norepinephrine turnover in organs and brains of obesity-prone rats

1995 ◽  
Vol 268 (2) ◽  
pp. R389-R394 ◽  
Author(s):  
B. E. Levin
Keyword(s):  
Energy Content ◽  
Sprague Dawley ◽  
Dorsomedial Nucleus ◽  
Interscapular Brown Adipose Tissue ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Lateral Area

One-half of the adult male Sprague-Dawley rats fed a diet relatively high in fat, sucrose, and energy content (HE diet) develop diet-induced obesity (DIO). The rest are diet resistant (DR). The role of peripheral and central norepinephrine (NE) activity in predisposing them to these weight gain patterns was assessed before HE diet exposure. Chow-fed male 3-mo-old Sprague-Dawley rats were separated as being prone to become DIO or DR by their high (3.06 +/- 0.14 micrograms) vs. low (1.17 +/- 0.10 micrograms; P = 0.001) 24-h urine NE output, respectively. Turnover of NE, an index of sympathetic activity, was assessed by synthesis inhibition with alpha-methyl-p-tyrosine. DIO-prone rats had significant 53 and 18% reductions in heart and pancreas NE turnover, with interscapular brown adipose tissue turnover comparable to that of DR-prone rats. Hypothalamic NE turnover was significantly decreased by 85 and 60% in the ventromedial nucleus and lateral area vs. DR-prone rats. Although present in DR-prone rats, no turnover was found in the dorsomedial nucleus of DIO-prone rats. Endogenous NE was reduced by 28% in the paraventricular nucleus, whereas arcuate/median eminence turnover was increased by 100% in DIO-prone rats. Amygdalar NE turnover was similar between phenotypes. These intrinsic differences in NE metabolism may play an important role in the development of DIO on HE diets.

Brown adipose and metabolic features of chronic diet-induced obesity

1985 ◽  
Vol 248 (6) ◽  
pp. R717-R723 ◽  
Author(s):  
B. E. Levin ◽  
M. Finnegan ◽  
J. Triscari ◽  
A. C. Sullivan
Keyword(s):  
Metabolic Efficiency ◽  
Sprague Dawley ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Plasma Insulin Levels

Half of the 3-mo male Sprague-Dawley rats fed a high-fat (DIO) diet for 5 mo became obese and had increased carcass lipid (106%) and plasma insulin levels (61%), despite 8% less total energy intake than chow-fed controls. Their interscapular brown adipose tissue (IBAT) was 52% heavier with 45% more lipid and larger uni- and multilocular cells. Norepinephrine turnover was normal in their hearts, pancreases, and aortas but undetectable in IBAT where in vitro lipolysis, but not O2 consumption (VO2), was enhanced. Half the rats fed the DIO diet ate 17% fewer calories, gained weight equally to controls, but still had 34% more carcass lipid. Their IBAT was heavier, contained 103% more protein, with no detectable norepinephrine turnover, whereas maximal lipolysis was 73% lower and maximal VO2 was the same or even lower than controls. IBAT VO2 was stimulated by switching 8-mo chow-fed controls to the DIO diet for 7 days (which caused a 480% greater weight gain) but not by switching 8-mo obese rats to chow for 3 days. Therefore metabolic efficiency was increased while BAT VO2 and norepinephrine turnover were unchanged or reduced compared with controls by either chronic obesity or a high-fat diet.

Defense of differfing body weight set points in diet-induced obese and resistant rats

1998 ◽  
Vol 274 (2) ◽  
pp. R412-R419 ◽  
Author(s):  
Barry E. Levin ◽  
Richard E. Keesey
Keyword(s):  
Body Weight ◽  
Diet Composition ◽  
Energy Homeostasis ◽  
Energy Content ◽  
Sprague Dawley ◽  
Fat Pad ◽  
Insulin Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Plasma Leptin

Among outbred Sprague-Dawley rats, approximately one-half develop diet-induced obesity (DIO) and one-half are diet resistant (DR) on a diet relatively high in fat and energy content (HE diet). Here we examined the defense of body weight in these two phenotypes. After HE diet for 13 wk, followed by chow for 6 wk, DR rats gained weight comparably but their plasma leptin levels fell to 54% of chow-fed controls. When a palatable liquid diet (Ensure) was added for 13 wk, other DR rats became obese. But when switched to chow, their intakes fell by 60%, and body and retroperitoneal (RP) fat pad weights and plasma leptin and insulin levels all declined for 2 wk and then stabilized at control levels after 6 wk. In contrast, comparably obese DIO rats decreased their intake by only 20%, and their weights plateaued when they were switched to chow after 13 wk on HE diet. When a subgroup of these DIO rats was restricted to 60% of prior intake, their weights fell to chow-fed control levels over 2 wk. But their leptin and insulin levels both fell disproportionately to 30% of controls. When no longer restricted, their intake and feed efficiency rose immediately, and their body and RP pad weights and leptin and insulin levels rose to those of unrestricted DIO rats within 2 wk. Thus diet and genetic background interact to establish high (DIO) or low (DR) body weight set points, which are then defended against subsequent changes in diet composition and/or energy availability. If leptin affects energy homeostasis, it does so differentially in DIO vs. DR rats since comparably low and high levels were associated with differing patterns of weight change between the two phenotypes.

Altered sympathetic activity during development of diet-induced obesity in rat

1983 ◽  
Vol 244 (3) ◽  
pp. R347-R355 ◽  
Author(s):  
B. E. Levin ◽  
J. Triscari ◽  
A. C. Sullivan
Keyword(s):  
Adipose Tissue ◽  
Lipid Content ◽  
Sympathetic Activity ◽  
Turnover Rates ◽  
Sprague Dawley ◽  
Interscapular Brown Adipose Tissue ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Obese Rats ◽  
Relative Body Weight

Sprague-Dawley rats developed diet-induced obesity (DIO) after 3 mo on a high-fat, high-sucrose diet (DIO diet), with associated increases in total body and interscapular brown adipose tissue (IBAT) lipid content. After 7 days on the DIO diet, rats had increased levels of tyrosine hydroxylase (TH; 34%), norepinephrine (NE; 34%), and NE turnover (94%; estimated by alpha-methyl-p-tyrosine inhibition of TH) in their IBAT compared with chow-fed controls. After 3 mo on the DIO diet, NE levels and/or turnover were reduced by 27–50% in aortas, hearts, and pancreata in obese rats. While IBAT NE turnover was normal, TH inhibition failed to increase the lipid content of IBAT in obese rats as it did in controls, suggesting a postsynaptic defect in basal NE-stimulated lipolysis in this thermogenically active tissue. When obese rats were switched from the DIO diet to rat chow for 3 days, NE levels remained depressed in their hearts (25%) and aortas (14%) but were increased by 36–45% in IBAT, pancreata, and white adipose tissue. NE turnover rates and/or constants were increased by 37–110% in hearts, aortas, pancreata, and IBAT of these obese rats while there were increased IBAT TH (20%) and dopamine-beta-hydroxylase (87%) activities compared with chow-fed controls. Therefore, sympathetic activity varied markedly as a function of both dietary composition and relative body weight during the development of DIO.

scholarly journals Defense of body weight depends on dietary composition and palatability in rats with diet-induced obesity

2002 ◽  
Vol 282 (1) ◽  
pp. R46-R54 ◽  
Author(s):  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell
Keyword(s):  
Body Weight ◽  
Energy Content ◽  
Selective Reduction ◽  
High Energy ◽  
Hypothalamic Nucleus ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Background Diet ◽  
Sprague Dawley Rats ◽  
Body Weights

Sprague-Dawley rats selectively bred for diet-induced obesity (DIO) or diet resistance (DR) were characterized on diets of differing energy content and palatability. Over 10 wk, DR rats on a high-energy (HE) diet (31% fat) gained weight similarly to DR rats fed chow (4.5% fat), but they became obese on a palatable liquid diet (Ensure). DIO rats gained 22% more weight on an HE diet and 50% more on Ensure than chow-fed DIO rats. DIO body weight gains plateaued when switched from HE diet to chow. But, Ensure-fed DIO rats switched to chow spontaneously reduced their intake and weight to that of rats switched from HE diet to chow. They also reduced their hypothalamic proopiomelanocortin and dynorphin but not neuropeptide Y mRNA expression by 17–40%. When reexposed to Ensure after 7 wk, they again overate and matched their body weights to rats maintained on Ensure throughout. All Ensure-fed rats had a selective reduction in dynorphin mRNA in the ventromedial hypothalamic nucleus. Thus genetic background, diet composition, and palatability interact to produce disparate levels of defended body weight and central neuropeptide expression.

Effects of diet and obesity on brown adipose metabolism

1984 ◽  
Vol 246 (5) ◽  
pp. E418-E425
Author(s):  
B. E. Levin ◽  
M. B. Finnegan ◽  
E. Marquet ◽  
J. Triscari ◽  
K. Comai ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Metabolic Activation ◽  
Mitochondrial Morphology ◽  
Sprague Dawley ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Obese Rats ◽  
And Control

The effect of diet-induced obesity on interscapular brown adipose tissue (IBAT) was assessed after feeding male Sprague-Dawley rats a high-fat diet for 3-5 mo beginning at 3 mo of age. IBAT pads in 6-mo-old obese rats were heavier (22%), had more lipid (71%), and larger unilocular cells (38%) than chow-fed controls. Mitochondrial morphology, beta-adrenergic receptor binding ([ 125I]iodocyanopindolol), and norepinephrine-stimulated lipolysis were similar in IBAT from obese and control rats. When 8-mo-old chow-fed rats were switched to the high-fat diet for 7-14 days, IBAT pads became hypercellular without cell hypertrophy and with a 70% increase in norepinephrine-induced lipolysis. However, when 8-mo-old obese rats that had been on the high-fat diet for 5 mo were switched to chow for 3 days, IBAT cellularity was unchanged, but norepinephrine-induced lipolysis was increased 70%. Therefore, in lean and obese 6- to 8-mo-old rats, short-term dietary manipulation led to metabolic activation, whereas chronic diet-induced obesity on a stable diet was associated with a return of IBAT metabolism to control levels.

Neostigmine in the hippocampus increases thermogenesis and T4-to-T3 conversion

1996 ◽  
Vol 270 (6) ◽  
pp. R1215-R1219 ◽  
Author(s):  
M. Monda ◽  
A. Papa ◽  
G. Brizzi ◽  
B. DeLuca
Keyword(s):  
Firing Rate ◽  
Blood Level ◽  
Sympathetic Nerves ◽  
O2 Consumption ◽  
Saline Injection ◽  
Sprague Dawley ◽  
Interscapular Brown Adipose Tissue ◽  
Sprague Dawley Rats ◽  
Brown Adipose ◽  
Baseline Values

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and TC), and O2 consumption were monitored in urethan-anesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a neostigmine (5 x 10(-7) mol) or saline injection in the hippocampus. The blood level of 3,5,3'-triiodothyronine and L-thyroxine (T3 and T4) and the 5'-deiodinating activity of IBAT, liver, and kidneys were determined in other rats with neostigmine or saline injection. The results showed that neostigmine injection increased firing rate, TIBAT, TC, O2 consumption, blood level of T3, and 5'-deiodinating activity of IBAT. No change was found in the T4 level and in 5'-deiodinating activity of the liver and kidneys. These findings suggest that neostigmine injection in the hippocampus increases heat production by stimulating sympathetic nerves to IBAT and by elevating the blood level of T3.

Lysine acetylsalicylate modifies aphagia and thermogenic changes induced by lateral hypothalamic lesion

1996 ◽  
Vol 271 (6) ◽  
pp. R1638-R1642 ◽  
Author(s):  
M. Monda ◽  
A. Sullo ◽  
E. De Luca ◽  
M. P. Pellicano
Keyword(s):  
Food Intake ◽  
Firing Rate ◽  
Intraperitoneal Injection ◽  
Intraperitoneal Administration ◽  
Sprague Dawley ◽  
Interscapular Brown Adipose Tissue ◽  
Sprague Dawley Rats ◽  
Brown Adipose ◽  
Before And After ◽  
Lysine Acetylsalicylate

These experiments test the effect of intraperitoneal injection of lysine acetylsalicylate on 1) food intake and 2) the sympathetic and thermogenic changes induced by lesion of the lateral hypothalamus (LH). Food intake, firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), and IBAT and colonic temperatures (TIBAT and TC) were monitored in male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after intraperitoneal injection of lysine acetylsalicylate. The same variables were also monitored in 1) lesioned rats with intraperitoneal administration of saline, 2) sham-lesioned animals with intraperitoneal injection of lysine acetylsalicylate, and 3) sham-lesioned rats with intraperitoneal injection of saline. The results show that lysine acetylsalicylate modifies the aphagia by increasing food intake and also reduces the enhancements in firing rate, TIBAT, and TC induced by LH lesion. These findings suggest that prostaglandin synthesis plays a key role in the control of eating behavior in LH-lesioned rats by acting on the sympathetic and thermogenic changes induced by LH lesion.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Plasma Catecholamines ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Prolonged Administration ◽  
Chronic Stimulation ◽  
Sustained Hypertension ◽  
Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate on Carbon tetrachloride Intoxicated Rats Model

2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Injury ◽  
Antioxidant Properties ◽  
Hepatic Necrosis ◽  
Protective Role ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Isolated Compound

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.

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