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.

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.

Ontogeny of diet-induced obesity in selectively bred Sprague-Dawley rats

2003 ◽  
Vol 285 (3) ◽  
pp. R610-R618 ◽  
Author(s):  
Matthew R. Ricci ◽  
Barry E. Levin
Keyword(s):  
Leptin Receptor ◽  
Splice Variants ◽  
Caloric Intake ◽  
High Energy ◽  
Sprague Dawley ◽  
Low Fat Diet ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Sprague Dawley Rats ◽  
Plasma Leptin

Outbred Sprague-Dawley rats selectively bred for their propensity to develop diet-induced obesity (DIO) become heavier on low-fat diet than those bred to be diet resistant (DR) beginning at ∼5 wk of age. Here we assessed the development of metabolic and neural functions for insights into the origins of their greater weight gain. From week 5 to week 10, chow-fed DIO rats gained 15% more body weight and ate ∼14% more calories but had only slightly greater adiposity and plasma leptin than DR rats. From day 3 through week 10, DIO and DR rats had similar mRNA expression of arcuate nucleus neuropeptide Y, proopiomelanocortin, agouti-related peptide, and all splice variants of the leptin receptor (OB-R). When fed a high-energy (HE; 31% fat) diet, 7-wk-old DIO rats had a 240% increase in plasma leptin levels after only 3 days. Despite this early leptin rise, they maintained a persistent hyperphagia and became more obese than chow-fed DIO rats and DR rats fed chow or HE diet. Their failure to reduce caloric intake, despite high levels of leptin, suggests that selectively bred DIO rats might have reduced leptin sensitivity similar to that seen in the outbred DIO parent strain.

scholarly journals Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity

2019 ◽  
Vol 8 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Anna C Simcocks ◽  
Kayte A Jenkin ◽  
Lannie O’Keefe ◽  
Chrishan S Samuel ◽  
Michael L Mathai ◽  
...  
Keyword(s):  
Body Weight ◽  
G Protein ◽  
High Fat Diet ◽  
Chow Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
G Protein Coupled Receptor ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
G Protein Coupled

Atypical cannabinoid compounds O-1602 and O-1918 are ligands for the putative cannabinoid receptors G protein-coupled receptor 55 and G protein-coupled receptor 18. The role of O-1602 and O-1918 in attenuating obesity and obesity-related pathologies is unknown. Therefore, we aimed to determine the role that either compound had on body weight and body composition, renal and hepatic function in diet-induced obesity. Male Sprague–Dawley rats were fed a high-fat diet (40% digestible energy from lipids) or a standard chow diet for 10 weeks. In a separate cohort, male Sprague–Dawley rats were fed a high-fat diet for 9 weeks and then injected daily with 5 mg/kg O-1602, 1 mg/kg O-1918 or vehicle (0.9% saline/0.75% Tween 80) for a further 6 weeks. Our data demonstrated that high-fat feeding upregulates whole kidney G protein receptor 55 expression. In diet-induced obesity, we also demonstrated O-1602 reduces body weight, body fat and improves albuminuria. Despite this, treatment with O-1602 resulted in gross morphological changes in the liver and kidney. Treatment with O-1918 improved albuminuria, but did not alter body weight or fat composition. In addition, treatment with O-1918 also upregulated circulation of pro-inflammatory cytokines including IL-1α, IL-2, IL-17α, IL-18 and RANTES as well as plasma AST. Thus O-1602 and O-1918 appear not to be suitable treatments for obesity and related comorbidities, due to their effects on organ morphology and pro-inflammatory signaling in obesity.

Initiation and perpetuation of obesity and obesity resistance in rats

1989 ◽  
Vol 256 (3) ◽  
pp. R766-R771 ◽  
Author(s):  
B. E. Levin ◽  
S. Hogan ◽  
A. C. Sullivan
Keyword(s):  
High Energy ◽  
The Body ◽  
Sprague Dawley ◽  
Fat Pad ◽  
Intravenous Glucose ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Fat Pads

A search was made for predisposing factors and sequelae of diet-induced obesity (DIO) or resistance to DIO (DR). During 3 mo on a high-energy (CM) diet, two-thirds of the male Sprague-Dawley rats ate 16% more calories over the first 30 days and developed DIO. The remaining one-third were DR, gaining the same amount of weight as chow-fed controls. Basal and norepinephrine (NE)-stimulated in vivo O2 consumption, performed before rats were placed on the CM diet, was the same in those rats that later became DR or DIO after 3 mo on the CM diet. DR rats were 4% lighter, whereas DIO rats were equal to chow-fed rats before their exposure to the CM diet. When CM-fed rats were switched to chow, DIO rats took 14 wk to reduce their body and retroperitoneal fat pad weights to those of chow-fed controls, whereas DR rats gained only 40% of the body weight, and fat pads were 34% lighter than controls. After 14 wk, DIO rats were neither hyperinsulinemic nor insulin resistant, whereas DR rats had 64% reduced areas under their insulin curves after intravenous glucose (1 g/kg) compared with controls. Unlike younger rats, animals here had inconsistent plasma NE responses to intravenous glucose. Therefore the CM diet produces DR and DIO states that tend to become self-perpetuating once established.

Diet cycling and age alter weight gain and insulin levels in rats

1994 ◽  
Vol 267 (2) ◽  
pp. R527-R535 ◽  
Author(s):  
B. E. Levin
Keyword(s):  
Weight Gain ◽  
Body Weight Gain ◽  
High Energy ◽  
Sprague Dawley ◽  
Insulin Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Plasma Insulin Levels ◽  
Diet Intake

For assessment of the effect of diet cycling on body weight gain patterns, 3-mo-old male Sprague-Dawley rats were either cycled from chow to a high-energy condensed milk (CM) diet, back to chow, and then back to CM diet at 3-mo intervals (cyclers) or were fed chow to 9 mo of age and then CM diet for 3 mo (noncyclers). Nine of 21 cyclers developed diet-induced obesity (DIO), gaining 36, 59, and 281% more weight than chow-fed controls (CF) at each cycle, respectively. Twelve cycled rats were diet-resistant (DR) with comparable weight gain to CF rats after the first CM diet and chow cycles. However, they gained 202% more than CF rats and 50% more, with 29% heavier retroperitoneal fat pads, than noncycled DR rats after their second CM diet cycle begun at 9 mo of age. Enhanced weight gain in DR cyclers was probably due to enhanced food efficiency in the last few weeks of CM diet intake. Plasma insulin levels were 70% higher in cycled vs. noncycled DIO and DR rats, and both were higher than CF rats. Unlike 6-mo-old DR rats in a prior study, 12-mo-old noncycled DR rats after 3 mo on CM diet here had 45-172% higher alpha 2-adrenoceptors binding in 6 of 17 brain areas than noncycled DIO and/or CF rats. Thus age, diet cycling, and brain alpha 2-adrenoceptors interact to affect long-term changes in weight gain and metabolism.

Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats

2000 ◽  
Vol 278 (1) ◽  
pp. R231-R237 ◽  
Author(s):  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell
Keyword(s):  
Caloric Restriction ◽  
High Energy ◽  
The Body ◽  
Male Rats ◽  
Sprague Dawley ◽  
Insulin Levels ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Plasma Leptin ◽  
Adipose Mass

Half of Sprague-Dawley rats develop and defend diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy (HE) diet. Here, adult male rats were made DIO or DR after 10 wk on HE diet. Then half of each group was food restricted for 8 wk on chow to maintain their body weights at 90% of their respective baselines. Rate and magnitude of weight loss were comparable, but maintenance energy intake and the degree of sympathetic activity (24-h urine norepinephrine) inhibition were 17 and 29% lower, respectively, in restricted DR than DIO rats. Restricted DIO rats reduced adipose depot weights, plasma leptin, and insulin levels by 35%. Restricted DR rats reduced none of these. When fed ad libitum, both DR and DIO rats returned to the body weights of their respective chow-fed phenotype controls within 2 wk. This was associated with increased adipose mass and leptin and insulin levels only in DIO rats. Thus DR rats appear to alter primarily their lean body mass, whereas DIO rats primarily alter their adipose mass during chronic caloric restriction and refeeding.

scholarly journals Melatonin Reduces Body Weight Gain in Sprague Dawley Rats with Diet-Induced Obesity

Endocrinology ◽  
2003 ◽  
Vol 144 (12) ◽  
pp. 5347-5352 ◽  
Author(s):  
Bénédicte Prunet-Marcassus ◽  
Mathieu Desbazeille ◽  
Arnaud Bros ◽  
Katie Louche ◽  
Philippe Delagrange ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats

scholarly journals Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats

2015 ◽  
Vol 225 (2) ◽  
pp. 113-124 ◽  
Author(s):  
Kayte A Jenkin ◽  
Lannie O'Keefe ◽  
Anna C Simcocks ◽  
Esther Grinfeld ◽  
Michael L Mathai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Obese Rats ◽  
Renal Tubular ◽  
Plasma Leptin

Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established; however, the direct effects of cannabinoid receptor 1 (CB1) antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO. Male Sprague–Dawley rats were fed a low- or high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks to elicit DIO (n=9). In a different cohort, rats were fed a HFD for 15 weeks. After 9 weeks consuming a HFD, rats were injected daily for 6 weeks with 3 mg/kg AM251 (n=9) or saline via i.p. injection (n=9). After 10 weeks consuming a HFD, CB1 and megalin protein expression were significantly increased in the kidneys of obese rats. Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats. Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinaemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGFA, TGFB1 and collagen IV in the kidney. This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats.

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.

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.

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