Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome

Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel; Lykkegaard, Kirsten; Tang-Christensen, Mads; Hansen, Harald S.; Levin, Barry E.; Larsen, Philip J.; Knudsen, Lotte Bjerre; Fosgerau, Keld; Vrang, Niels

doi:10.1677/joe-10-0004

Cited by 140 publications

(144 citation statements)

References 42 publications

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“…Besides their weight reducing effects, and in agreement with previously published data, liraglutide was able to improve glucose tolerance [14] , and sibutramine improved the insulin sensitivity index (ISI) [10] . The latter was primarily obtained via reductions in glucose-stimulated insulin secretion.…”

Section: Wwwchinapharcom Hansen G Et Alsupporting

confidence: 90%

“…Since then, numerous DIO models have been published using the general approach whereby diets composed of alternating components of fat and carbohydrates are administered to normal, lean rats or mice over long periods [8,10,20] . The so-called cafeteria diets, where animals have a choice of various palatable foods such as chocolate, peanuts etc, encourages overeating and hence provides highly relevant models for examining human diets in rodents [15,[21][22][23] .…”

Section: Wwwnaturecom/aps Hansen G Et Almentioning

confidence: 99%

“…One such polygenic model is the diet-induced obese (DIO) and diet-resistant (DR) outbred rat models [7][8][9][10] . In the Levin DIO-rats, phenotypic differences in body weight gain, adiposity, and insulin sensitivity are only expressed between the outbred substrains when they are placed on diets of moderate fat, sucrose, and caloric content [11] .…”

Section: Introductionmentioning

confidence: 99%

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Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

2012

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Aim: To validate the gubra DIO-rats as a useful animal model of human obesity. Methods: The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 µg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d. Results: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubradiet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion. Conclusion: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference.

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Section: Wwwchinapharcom Hansen G Et Alsupporting

confidence: 90%

Section: Wwwnaturecom/aps Hansen G Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

2012

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“…For this purpose, the high-fat diet (HF)-induced obese rat model was selected, which has been shown to represent human obesity syndrome (14).…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: Role of brain mitochondrial KATP channels

Yang

Chen

Zhang

et al. 2014

Molecular Medicine Reports

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Abstract. Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning-induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet-induced obesity. Sprague-Dawley rats were fed a high-fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low-fat diet (LF; 10% kcal as fat) served as controls. The HF or LF-fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial K ATP (mitoK ATP ) channel was analyzed by the administration of a selective inhibitor of 5-hydroxydecanoate (5-HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoK ATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF-fed rats had larger infarct volumes, and lower neurological scores than the LF-fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF-fed rats. Pretreatment with 5-HD inhibited sevoflurane-induced neuroprotection in the LF-fed rats, whereas it had no effect in the HF-fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoK ATP channel component, was reduced in the brains of the HF-fed rats compared with the LF-fed rats. The results of this study indicate that diet-induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain mitoK ATP channel.

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“…DIO rats fed a high-energy (HE) diet develop the obese phenotype in contrast to diet-resistant (DR) rats that maintain normal body weight on an HE diet [18][19][20][21][22][23] .This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it is established in the DIO rat model. Among the neuronal factors regulating energy intake, a recently discovered orexigenic neuropeptide relaxin-3 [24,25] and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight.…”

Section: Introductionmentioning

confidence: 99%

The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

Lenglos

Calvez

Timofeeva

2014

Receptor Clin Invest

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Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it development in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in thead libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitumfed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype.

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Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome

Cited by 140 publications

References 42 publications

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: Role of brain mitochondrial KATP channels

The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

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