Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats

1997 ◽  
Vol 273 (2) ◽  
pp. R725-R730 ◽  
Author(s):  
B. E. Levin ◽  
A. A. Dunn-Meynell ◽  
B. Balkan ◽  
R. E. Keesey
Keyword(s):  
Glucose Tolerance ◽  
Tolerance Test ◽  
Male Rats ◽  
Oral Glucose ◽  
Chow Diet ◽  
Sprague Dawley ◽  
Fed State ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats

In outbred Sprague-Dawley rats, about one-half develop diet-induced obesity (DIO) on a diet relatively high in fat and energy (HE diet). The rest are diet resistant (DR), gaining weight and fat at the same rate as chow-fed controls. Here we selectively bred for high (DIO) and low (DR) weight gainers after 2 wk on HE diet. By the F5 generation, both male and female inbred DIO rats gained > 90% more weight than inbred DR rats on HE diets. Even on low-fat chow diet, DIO males were 31% and females were 22% heavier than their respective DR rats. Full metabolic characterization in male rats showed that weight-matched, chow-fed DIO-prone rats had similar energy intakes and feed efficiency [body weight (kg0.75)/energy intake (kcal)] but 44% more carcass fat than comparable DR-prone rats. Their basal plasma insulin and glucose levels in the fed state were 70 and 14% higher, respectively. But, when fasted, DIO-prone oral glucose tolerance results were comparable to DR-prone rats. Chow-fed DIO-prone males also had 42% greater 24-h urine norepinephrine levels than DR-prone males. During 2 wk on HE diet, DIO rats ate 25% more, gained 115% more weight, had 36% more carcass fat, and were 42% more feed efficient than comparable DR rats. Fasted HE diet-fed DIO rats developed frank glucose intolerance during a glucose tolerance test with 55 and 158% greater insulin and glucose areas under the curve, respectively. Thus the DIO and DR traits in the outbred Sprague-Dawley population appear to be due to a polygenic pattern of inheritance.

Effects of Different Fasting Durations on Glucose and Lipid Metabolism in Sprague Dawley Rats

2019 ◽  
Vol 51 (08) ◽  
pp. 546-553
Author(s):  
Elin Rakvaag ◽  
Majbritt Dam Lund ◽  
Lars Wiking ◽  
Kjeld Hermansen ◽  
Søren Gregersen
Keyword(s):  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Sprague Dawley ◽  
Glucose And Lipid Metabolism ◽  
Sprague Dawley Rats ◽  
Fat Tolerance Test ◽  
Fasting Duration

AbstractOvernight fasting of varying length is common practice when studying glucose and lipid metabolism in rats. However, prolonged fasting may influence insulin sensitivity, and it is unknown to which extent different fasting durations affect postprandial metabolism in rats. The purpose of this study was to investigate the effect of different fasting durations (6-, 12-, or 18-h) on fat tolerance and glucose tolerance in male Sprague Dawley rats. We also aimed to examine the effect of two test fats with different fatty acid composition on postprandial triglycerides. We conducted a fat tolerance test, where butterfat or rapeseed oil was administered in a crossover design (experiment 1), and an oral glucose tolerance test (experiment 2). Regarding the fat tolerance test, we found no effects of fasting duration on triglycerides or free fatty acids, whereas the 18-h fast resulted in reduced glucose and insulin area under the curves. We did not find differential effects of butterfat and rapeseed oil on the outcomes. We found decreased fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR), and increased beta-hydroxybutyric acid concentrations after 18-h fast compared with shorter fasting durations. Regarding the oral glucose tolerance test, both 12-h and 18-h fast resulted in greater peak insulin concentrations than 6-h fast, and peak glucose concentrations were higher after 18-h than 12-h fast. We found no effects of fasting on the insulin sensitivity index. In conclusion, extending the fasting duration had an impact on glucose metabolism in rats, but did not appear to influence fat tolerance.

scholarly journals Preliminary phytochemical screening and evaluation of hypoglycemic properties of the root extract of Uveria chamae

2015 ◽  
Vol 10 (2) ◽  
pp. 326 ◽  
Author(s):  
Emordi Jonathan Emeka ◽  
Agbaje Esther Oluwatoyin ◽  
Oreagba Ibrahim Adekunle ◽  
Iribhogbe Osede Ignis
Keyword(s):  
Single Dose ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Phytochemical Screening ◽  
Glucose Levels ◽  
Blood Glucose Levels

<p>The purpose of this study is to evaluate the hypoglycaemic properties and preliminary phytochemical screening of <em>Uveria chamae</em>. The hypoglycaemic properties of <em>Uveria chamae</em> was assessed on normoglycaemic rat that received single dose of the extract at 250 and 500 mg/kg body weight and blood glucose levels estimated at 2, 4, and 6 hours (single dose study). The hypoglycaemic property of the extract was also evaluated in normoglycemic rats by oral glucose tolerance test. Phytochemical screening of the extract for the presence of secondary metabolites was performed with standard methods. The extract showed a significant (p&lt;0.05) reduction in blood glucose levels at 2h and 6h compared to control.  The oral glucose tolerance test  result also showed a significant decrease (p&lt;0.05) in blood glucose levels . The study showed that the extract, <em>Uveria chamae</em> has hypoglycaemic properties which may be accounted for by the presence of the phytochemicals.</p><p> </p>

Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study

2011 ◽  
Vol 19 (4) ◽  
pp. 755-764 ◽  
Author(s):  
SS Anand ◽  
GR Dagenais ◽  
V Mohan ◽  
R Diaz ◽  
J Probstfield ◽  
...  
Keyword(s):  
Cohort Study ◽  
Glucose Tolerance ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Newly Diagnosed ◽  
Men And Women ◽  
Glucose Levels ◽  
Death Event ◽  
Lower Glucose ◽  
Artery Disease

Aims: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. Methods and results: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0–4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM ( p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13–1.22). Conclusions: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

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.

scholarly journals Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana M. Cruz ◽  
Katie M. Partridge ◽  
Yasaman Malekizadeh ◽  
Julia M. Vlachaki Walker ◽  
Paul G. Weightman Potter ◽  
...  
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Sprague Dawley ◽  
Autonomic Nervous ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Amp Activated Protein Kinase

AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.ResultsIn vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.

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