Characterization of Obesity Phenotypesin <i>Psammomys Obesus</i> (Israeli Sand Rats)

Walder, Ken; Fahey, R. P.; Morton, G.; Zimmet, Paul; Collier, Greg R.

doi:10.1155/edr.2000.177

Cited by 54 publications

(46 citation statements)

References 25 publications

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“…However, when housed in a laboratory setting and given ad libitum access to standard rodent laboratory diet, a proportion of the animals develop a range of metabolic abnormalities, including insulin resistance, obesity, type 2 diabetes, and dyslipidemia (6 -12). The distributions of body weight, blood glucose, and plasma insulin concentrations are continuous across the population of P. obesus (7,10) and closely approximate the distributions observed in human cross-sectional data (13,14).…”

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confidence: 65%

Tanis: A Link Between Type 2 Diabetes and Inflammation?

et al. 2002

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Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P ‫؍‬ 0.010) and insulin levels (P ‫؍‬ 0.004) and in direct proportion with plasma triglyceride concentrations (P ‫؍‬ 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P ‫؍‬ 0.006) as well as in several other cell types (P ‫؍‬ 0.001-0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.

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confidence: 65%

Tanis: A Link Between Type 2 Diabetes and Inflammation?

et al. 2002

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“…We have been investigating the development of obesity and type 2 diabetes in Psammomys obesus for several years, and the results of this study add to our contention that these rodents are an excellent polygenic animal model of obesity and type 2 diabetes. 12,13 Our investigations in Psammomys obesus now include concerted attempts to identify skeletal muscle substrates of CAPN3 that may be involved in the development of obesity and type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Classification as obese or lean was based on previously published criteria. 13 Part 2. To further investigate the relationship between calpain 3 gene expression in skeletal muscle and metabolism, a separate group of 22 non-diabetic Psammomys obesus was studied.…”

Section: Calpain 3 Obesity and Insulin Resistance K Walder Et Almentioning

confidence: 99%

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Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance

et al. 2002

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OBJECTIVE:To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance. DESIGN: Cross-sectional studies in 27 non-diabetic human subjects and in Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes. MEASUREMENTS: Expression of CAPN3 in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic -hyperinsulinemic clamp. In Psammomys obesus, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry. RESULTS: In human subjects, calpain 3 gene expression was negatively correlated with total (P ¼ 0.022) and central abdominal fat mass (P ¼ 0.034), and with blood glucose concentration in non-obese subjects (P ¼ 0.017). In Psammomys obesus, calpain 3 gene expression was negatively correlated with circulating glucose (P ¼ 0.013) and insulin (P ¼ 0.034), and with body fat mass (P ¼ 0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (P ¼ 0.009) and energy expenditure (P ¼ 0.013). CONCLUSION=INTERPRETATION: Lower levels of expression of calpain 3 in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of calpain 3 in both humans and Psammomys obesus was associated with phenotypes related to obesity and insulin resistance.

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“…[14][15][16][17] This model has been used to identify genes and metabolic pathways that influence the development of metabolic syndrome and have demonstrated associations with these traits in large human cohorts including ubiquitin-like 5 (refs 18,19) and selenoprotein S. 20 SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) was first discovered by differential display PCR analysis of hypothalamus RNA from lean and obese P. obesus and was found to be exclusively expressed in the central nervous system. 16 SGIP1 expression was increased in the hypothalamus of obese P. obesus and the encoded 828 amino-acid protein colocalized with POMC and NPY, two neuropeptides involved in the regulation of energy balance.…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

et al. 2011

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Objective: The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease. Subjects: We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass. Results: Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P ¼ 4.7 Â 10 À5 ). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele. Conclusions: Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans.

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Characterization of Obesity Phenotypesin Psammomys Obesus (Israeli Sand Rats)

Cited by 54 publications

References 25 publications

Tanis: A Link Between Type 2 Diabetes and Inflammation?

Tanis: A Link Between Type 2 Diabetes and Inflammation?

Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance

Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

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