Ldlr−/− Mice Display Decreased Susceptibility to Western-Type Diet-Induced Obesity Due to Increased Thermogenesis

Ngai, Ying Fai; Quong, Whitney L.; Glier, Melissa B.; Glavas, Maria M.; Babich, Sandra L.; Innis, Sheila M.; Kieffer, Timothy J.; Gibson, William T.

doi:10.1210/en.2010-0496

Cited by 26 publications

(23 citation statements)

References 47 publications

(35 reference statements)

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“…These mice also gained less weight in response to dietary intervention. Metabolic differences such as lower epididymal adipose tissue weight, lower body weight, and improved glucose tolerance under a HFD were previously reported in LDLr Ϫ/Ϫ mice and could at least be partially explained by an enhanced thermogenesis, but this observation on weight gain was not reproduced in one study with diets richer in carbohydrates, suggesting complex genetic-dietary interactions (20,24). Despite the lack of increased plasma glucose in LDLr Ϫ/Ϫ mice following prolonged high-cholesterol feeding, a study showed increased plasma insulin hinting at the existence of insulin resistance in these animals independent of weight gain (11).…”

Section: Discussionmentioning

confidence: 81%

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models

Laplante

Charbonneau

Avramoglu

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionmentioning

confidence: 81%

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models

Laplante

Charbonneau

Avramoglu

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Resistance against diet-induced obesity has also been reported for the low-density lipoprotein receptor knockout mouse model. 23 Both cholesterolemia and triglyceridemia were similarly increased in LRKOB100 and LRKOB100/ IGF mice as compared with WT on either diet ( Figure 1C and 1D). These data thus indicate that LRKOB100/IGF mice are prone to T2D, after only 6 months of feeding a diabetogenic diet.…”

Section: Metabolic Phenotypes Of Lrkob100 and Lrkob100/igf Micementioning

confidence: 79%

Early Development of Calcific Aortic Valve Disease and Left Ventricular Hypertrophy in a Mouse Model of Combined Dyslipidemia and Type 2 Diabetes Mellitus

Quang

Bouchareb

Lachance

et al. 2014

ATVB

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Objective— This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. Approach and Results— When compared with nondiabetic LDLr −/− /ApoB 100/100 , diabetic LDLr −/− /ApoB 100/100 /IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr −/− /ApoB 100/100 /IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr −/− /ApoB 100/100 mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr −/− /ApoB 100/100 /IGF-II mice when compared with LDLr −/− /ApoB 100/100 . Importantly, we found that peak aortic jet velocity was significantly increased in LDLr −/− /ApoB 100/100 /IGF-II mice versus LDLr −/− /ApoB 100/100 animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes ( anp , bnp , b-mhc ) in myocardial tissues and of osteogenic genes ( spp1 , bglap , runx2 ) in aortic tissues of diabetic mice. Conclusions— We have established the diabetes mellitus –prone LDLr −/− /ApoB 100/100 /IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis.

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“…This augmented T cell response occurred in the absence of any excess weight gain or IL-6 production, indicating that a diet-induced proinflammatory environment did not cause the altered T cell response. This is because LDLr 2/2 mice gain less weight and fat mass when fed a WHF diet compared with LDLr +/+ mice on the same background and are thus less prone to obesity and obesity-induced inflammation (45)(46)(47). Of interest, an acute dietary intervention of 1 wk did not alter the T cell response in CHS, likely because the lipid composition of T cells had not changed after 1 wk of WHF diet and/or owing to enhanced (polarized) innate inflammatory responses to the acute high-fat feeding (48), at the expense of a lower T cell response.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Pollock

Tedla

Hancock

et al. 2016

The Journal of Immunology

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Although it is recognized that lipids and membrane organization in T cells affect signaling and T cell activation, to what extent dietary lipids alter T cell responsiveness in the absence of obesity and inflammation is not known. In this study, we fed low-density lipoprotein receptor knockout mice a Western high-fat diet for 1 or 9 wk and examined T cell responses in vivo along with T cell lipid composition, membrane order, and activation ex vivo. Our data showed that high levels of circulating lipids for a prolonged period elevated CD4+ and CD8+ T cell proliferation and resulted in an increased proportion of CD4+ central-memory T cells within the draining lymph nodes following induction of contact hypersensitivity. In addition, the 9-wk Western high-fat diet elevated the total phospholipid content and monounsaturated fatty acid level, but decreased saturated phosphatidylcholine and sphingomyelin within the T cells. The altered lipid composition in the circulation, and of T cells, was also reflected by enhanced membrane order at the activation site of ex vivo activated T cells that corresponded to increased IL-2 mRNA levels. In conclusion, dietary lipids can modulate T cell lipid composition and responses in lipoprotein receptor knockout mice even in the absence of excess weight gain and a proinflammatory environment.

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Ldlr−/− Mice Display Decreased Susceptibility to Western-Type Diet-Induced Obesity Due to Increased Thermogenesis

Abstract: The low-density lipoprotein receptor (Ldlr) is a key molecule involved with lipid clearance. The Ldlr Ϫ/Ϫ mouse has been used extensively as a model for studying atherosclerosis.

Cited by 26 publications

References 47 publications

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models

Early Development of Calcific Aortic Valve Disease and Left Ventricular Hypertrophy in a Mouse Model of Combined Dyslipidemia and Type 2 Diabetes Mellitus

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

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