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

Levin, Barry E.; Dunn-Meynell, Ambrose A.; Balkan, Börk; Keesey, Richard E.

doi:10.1152/ajpregu.1997.273.2.r725

Cited by 402 publications

(553 citation statements)

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“…6,7,14,18,[46][47][48][49] They have also been detected in adult OP rats at normal weight, although endogenous NPY, in addition to a suppression, may show no change or even an increase, depending in part on its level of sensitivity to the inhibitory actions of leptin and insulin. [7][8][9]16,50 These findings demonstrate that rats, identified as OP before puberty based on their slightly elevated weight gain, exhibit as adults a typical phenotype associated with obesity.…”

Section: Discussionmentioning

confidence: 99%

“…For example, in adult SpragueDawley rats on pure macronutrient or fat-rich diets, measures of weight gain, energy intake or fat preference are found to vary considerably in direct proportion to ultimate body fat accrual, [1][2][3][4][5] with the weight-gain measure providing the basis for selective breeding of rats prone vs resistant to obesity. 6,7 This variability has enabled investigators to identify measures in adult rats, at normal body weight, that can accurately and reproducibly differentiate distinct subgroups that are obesity-prone (OP) or obesity-resistant (OR). These markers of obesity include initial weight gain during the first few days on a high-fat diet, 1,8 levels of leptin after a single high-fat meal in rats maintained on a lab chow diet, 9 meal-induced release of insulin 10 and fasting levels of triglycerides or basal growth hormone secretion in rats on chow.…”

Section: Introductionmentioning

confidence: 99%

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Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight

et al. 2007

Int J Obes

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Objective: Male Sprague-Dawley rats maintained from birth on a high-fat diet were examined to determine whether a specific measure before puberty can identify and allow one to characterize prepubertal rats at normal weight with high vs low risk for adult obesity. Materials and methods: Measures from weaning (day 21) to around puberty (day 45) were taken of weight gain, absolute body weight and daily energy intake on a high-fat diet and related to the amount of body fat accumulated at maturity (80-100 days of age). Rats identified by a specific prepubertal measure as obesity-prone (OP) vs obesity-resistant (OR) were then characterized before and after puberty. Results: Prepubertal weight gain from days 30 to 35 of age was the strongest and earliest positive correlate of ultimate body fat accrual in adult rats. The highest (8-10 g/day) compared to lowest (5-7 g/day) weight-gain scores identified accurately and reproducibly distinct OP and OR subgroups at day 35 that became obese or remained lean, respectively, as adults. The OP rats with rapid prepubertal weight gain and 50% greater adiposity at maturity (day 100) exhibited the expected phenotype of already-obese rats. These included elevated levels of leptin, insulin, triglycerides and glucose, increased galanin (GAL) peptide levels in the paraventricular nucleus (PVN) and reduced neuropeptide Y (NPY) levels in the arcuate nucleus (ARC). Before puberty (day 35), the OP rats with normal fat pad weights, energy intake and endocrine profile similar to OR rats exhibited these disturbances characteristic of obese rats. They had decreased capacity for fat oxidation in muscle, increased GAL expression in PVN and reduced expression of NPY and agouti-related protein in ARC. Conclusion: Prepubertal weight gain can identify OP rats on day 35 when they have minimal body fat but exhibit specific metabolic and neurochemical disturbances expected to promote obesity and characteristics of already-obese adult rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight

et al. 2007

Int J Obes

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“…Acute studies (meal pattern analyses and locomotor activity) used male Harlan SpragueDawley rats (Harlan, Indianapolis, IN, USA) maintained on a moderately high-fat diet (32% kcal from fat; D12266B, Research Diets, New Brunswick, NJ, USA). Sustained infusion studies were conducted using in-bred male DIO-prone 19 male rats (Charles Rivers Labs, Wilmington, MA, USA) that were fattened for 6 weeks on a moderately high-fat diet (32% kcal from fat; Research Diets no. D12266B) and maintained ad libitum on this diet during testing.…”

Section: Methodsmentioning

confidence: 99%

“…To test this, we examined the individual and combined effects of these agents on changes in food intake, body weight and adiposity in DIO rats, an accepted surrogate model of human obesity. 19 …”

Section: Introductionmentioning

confidence: 99%

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

Roth¹,

Trevaskis²,

Wilson³

et al. 2008

Int J Obes

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Objective: To characterize the interactive effects of amylin with phentermine or sibutramine on food intake, body weight/ composition and gene expression in diet-induced obese (DIO) rats. Design: DIO rats were intraperitoneally injected with a single dose of amylin (10 mg kg À1 ) and/or phentermine (1 mg kg À1 ) or chronically infused with amylin (100 mg kg À1 d À1 ) or vehicle with or without phentermine (0.5-10 mg kg À1 d À1 ) or sibutramine (3 mg kg À1 d À1 ) using two surgically implanted subcutaneous osmotic mini-pumps. Measurements: Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, phentermine or amylin þ phentermine). Body weight and composition (for amylin and/or sibutramine or phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (b-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or phentermine) after sustained infusion (2 weeks). Results: Acute co-administration of amylin (10 mg kg À1 ) and phentermine (1 mg kg À1 ) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain (B4-8%). Phentermine's anorexigenic (10-17%) and weightreducing effects (B0-5%) were only evident at the highest dose tested (10 mg kg À1 d À1 ). Combination of amylin (100 mg kg À1 d À1 ) and phentermine reduced food intake (30-43%), body weight (8-12%) and adiposity to a greater extent than either monotherapy. Amylin prevented phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin þ sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin þ phentermine treatment, amylin þ sibutramine mediated weight loss was attributable to significant reductions in fat mass. Conclusions: Combined treatment of DIO rats with the pancreatic b-cell hormone amylin and phentermine or sibutramine resulted in additive anorexigenic, weight-and fat-reducing effects.

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“…Both diets were custom-prepared (Teklad Corporation, Madison, WI, USA; TD.85 080: LFCC diet, TD.83 402: HFS diet; Table 1) and were selected based on prior research (19,20,21) . Diets were designed to differ in energy density in order to address differences in bone mechanical properties between a high-energy-dense diet (HFS) and a lowenergy-dense diet (LFCC).…”

Section: Dietary Regimenmentioning

confidence: 99%

High-fat, sucrose diet impairs geometrical and mechanical properties of cortical bone in mice

et al. 2009

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Exposure to diets high in fat and sucrose can induce hyperinsulinaemia, affect Ca and Mg metabolism, and alter bone mineralisation and mechanical properties. The present study assessed morphological and mechanical changes in a murine model exposed to a high-fat/sucrose (HFS) diet, as well as corresponding molecular and endocrine markers of bone turnover. Female C57BL/6 mice (aged 9 weeks) consumed either a low-fat, complex carbohydrate diet or an HFS diet for 10 weeks. At the end of the 10 weeks, serum was collected for biochemical analysis. Tibiae from half the mice (n 15) were randomly selected to be micro-computed tomography scanned and tested to failure in cantilever bending, while the remaining half were prepared for real-time PCR analysis. Serum tartrate-resistant acid phosphatase was significantly elevated in HFS mice, while osteocalcin remained unchanged. Both body mass and percentage body fat were greater in mice fed HFS diet. After adjusting for body mass, tibial structural and morphological properties were adversely affected in the HFS cohort. Cortical thickness, cross-sectional area, and load at maximum were all significantly lower in mice fed HFS diet. Receptor activator of nuclear factor kb ligand (RANKL) mRNA was significantly upregulated in HFS mice, but osteoprotegerin/RANKL mRNA ratio remained unchanged between cohorts. Moreover, cyclo-oxygenase-2 mRNA tended to be increased in HFS. Thus, ingestion of an HFS diet had a significant adverse effect on mouse bone morphology and mechanics, and these effects were likely due to elevated osteoclast activity associated with the inflammatory state of obesity, and not necessarily osteoclast recruitment/ proliferation.Cortical bone: High-fat/sucrose diet: Biomechanics: C57BL/6 mice The changing face of disease aetiology over the past century has brought to the forefront the need to examine the environmental or modifiable risk factors that have influenced the epidemic of chronic disease afflicting a majority of the Western world. Nutritional status is a readily modifiable risk factor linked to numerous chronic conditions, including CHD, cancer, obesity, diabetes and osteoporosis (1,2) . Nonetheless, despite the prevalence of research linking poor dietary choices to chronic disease status, the nutritional patterns presently dominating most Western nations continue to be high in saturated fats, Na and refined carbohydrates from sugars, cereals and dairy products, and low in fruits, vegetables and lean protein (3) .Considerable effort has focused on discovering the underlying nutritional factors that predispose an individual to osteopenia or osteoporosis and subsequent fracture (4) . Much research has concentrated on the role of Ca and vitamin D metabolites influencing bone morphology and mechanics; however, macronutrients such as fat, protein and carbohydrate also play a vital role in bone health (5) . Considered independently, consumption of diets composed of large amounts of saturated fat has been documented to cause the formation of insoluble soap complexe...

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

Cited by 402 publications

References 0 publications

Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight

Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

High-fat, sucrose diet impairs geometrical and mechanical properties of cortical bone in mice

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