Impact of Chromosome 2 Obesity Loci on Cardiovascular Complications of Insulin Resistance in LDL Receptor–Deficient C57BL/6 Mice

Estrada-Smith, Daria; Collins, Alan R.; Wang, Xuping; Crockett, Craig; Castellani, Lawrence W.; Lusis, Aldons J.; Davis, Richard C.

doi:10.2337/db06-0377

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…Variation in genes identified in mice has been shown to affect the corresponding phenotypes in humans (24,52,75). These studies have also identified potential relations between MetS traits, showing that the same or nearby genes affect multiple MetS components (37,140).…”

Section: Use Of Mouse Models In Dissecting Metsmentioning

confidence: 88%

Genetics of metabolic syndrome: potential clues from wild-derived inbred mouse strains

Karunakaran

Clee

2018

Physiological Genomics

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The metabolic syndrome (MetS) is a complex constellation of metabolic abnormalities including obesity, abnormal glucose metabolism, dyslipidemia, and elevated blood pressure that together substantially increase risk for cardiovascular disease and Type 2 diabetes. Both genetic and environmental factors contribute to the development of MetS, but this process is still far from understood. Human studies have revealed only part of the underlying basis. Studies in mice offer many strengths that can complement human studies to help elucidate the etiology and pathophysiology of MetS. Here we review the ways mice can contribute to MetS research. In particular, we focus on the information that can be obtained from studies of the inbred strains, with specific focus on the phenotypes of the wild-derived inbred strains. These are newly derived inbred strains that were created from wild-caught mice. They contain substantial genetic variation that is not present in the classical inbred strains, have phenotypes of relevance for MetS, and various mouse strain resources have been created to facilitate the mining of this new genetic variation. Thus studies using wild-derived inbred strains hold great promise for increasing our understanding of MetS.

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Section: Use Of Mouse Models In Dissecting Metsmentioning

confidence: 88%

Genetics of metabolic syndrome: potential clues from wild-derived inbred mouse strains

Karunakaran

Clee

2018

Physiological Genomics

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“…In contrast, although the MOB6 congenic showed comparable glucose levels to the LDLR Ϫ/Ϫ strain, atherosclerosis was 2-fold reduced in this strain. 104 Plasma lipids and lipoprotein profiles were nearly identical between MOB6 and MOB5 strains. This study illustrates that individual traits associated with the metabolic syndrome can be separated and that insulin resistance was more important for promoting atherosclerotic lesions than elevated plasma glucose levels.…”

Section: Genome Scanningmentioning

confidence: 88%

“…103 The separation of glucose and atherosclerosis was also seen in a study of 2 congenic strains of C57BL/6 carrying loci derived from CAST/Ei (CAST). 104 Two regions of chromosome 2 alleles from CAST mice were introgressed into the C57BL/6 background and subsequently bred to LDLR Ϫ/Ϫ mice to create hyperlipidemic backgrounds for the CAST alleles. Mice fed chow and Western diets were studied for measures of glucose and lipid homeostasis and atherosclerosis.…”

Section: Genome Scanningmentioning

confidence: 99%

Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques?

Kanter

Johansson

LeBoeuf

et al. 2007

Circulation Research

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Abstract-It is becoming increasingly clear that suboptimal blood glucose control results in adverse effects on large blood vessels, thereby accelerating atherosclerosis and cardiovascular disease, manifested as myocardial infarction, stroke, and peripheral vascular disease. Cardiovascular disease is accelerated by both type 1 and type 2 diabetes. In type 1 diabetes, hyperglycemia generally occurs in the absence of elevated blood lipid levels, whereas type 2 diabetes is frequently associated with dyslipidemia. In this review article, we discuss hyperglycemia versus hyperlipidemia as culprits in diabetes-accelerated atherosclerosis and cardiovascular disease, with emphasis on studies in mouse models and isolated vascular cells. Recent studies on LDL receptor-deficient mice that are hyperglycemic, but exhibit no marked dyslipidemia compared with nondiabetic controls, show that diabetes in the absence of diabetes-induced hyperlipidemia is associated with an accelerated formation of atherosclerotic lesions, similar to what is seen in fat-fed nondiabetic mice. These effects of diabetes are masked in severely dyslipidemic mice, suggesting that the effects of glucose and lipids on lesion initiation might be mediated by similar mechanisms. Recent evidence from isolated endothelial cells demonstrates that glucose and lipids can induce endothelial dysfunction through similar intracellular mechanisms. Analogous effects of glucose and lipids are also seen in macrophages. Furthermore, glucose exerts many of its cellular effects through lipid mediators. We propose that diabetes without associated dyslipidemia accelerates atherosclerosis by mechanisms that can also be activated by hyperlipidemia. (Circ Res. 2007;100:769-781.)

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“…Studies in hypertensive rats (SHHR) and mice (eNos 3null ) have contributed a wealth of knowledge regarding how hypertension may impact morbidity and mortality either in isolation or in the context of the metabolic syndrome [5,6]. Similarly, diet-induced and spontaneous models of dyslipidemia in mice, such as the Ldlr null and ApoE null strains are providing clues to how alterations in circulating lipids may exacerbate cardiovascular disease [7,8]. Finally, models where hyperglycemia results from a genetic mutation (Ins2 Akita ), or following autoimmune attack of pancreatic beta cells (NOD Mouse, BB Rat), are providing systems to test the role of hyperglycemia in the array of pathophysiologies associated with metabolic syndrome [9,10].…”

mentioning

confidence: 98%

Animal Models of Obesity and Metabolic Syndrome: Potential Tools for Alzheimers Disease Research

Abraham

2007

CAR

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Emerging evidence suggests that components of the metabolic syndrome either in isolation or in aggregate may impact the onset or severity of neurodegenerative processes, including those physiologic changes that lead to Alzheimer's Disease (AD). Several animal models that were originally designed to interrogate the metabolic syndrome are readily available. These models can now be used to support studies that may provide new mechanistic links between the metabolic syndrome and neurodegeneration. In addition, animal strains currently being generated and phenotyped through the efforts of an array of NIDDK-supported projects are likely to provide novel and better tools to advance Alzheimer's disease research in the near future.

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Impact of Chromosome 2 Obesity Loci on Cardiovascular Complications of Insulin Resistance in LDL Receptor–Deficient C57BL/6 Mice

Cited by 9 publications

References 30 publications

Genetics of metabolic syndrome: potential clues from wild-derived inbred mouse strains

Genetics of metabolic syndrome: potential clues from wild-derived inbred mouse strains

Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques?

Animal Models of Obesity and Metabolic Syndrome: Potential Tools for Alzheimers Disease Research

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