Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats

Pravenec, Michal; Landa,; Zídek,; Musilová, Alena; Křen,; Kazdová, Ludmila; Tj, Aitman; Am, Glazier; Ibrahimi, Azeddine; Na, Abumrad; Qi, Nanshan; Jm, Wang; Em, St Lezin; Tw, Kurtz

doi:10.1038/84777

Cited by 184 publications

(138 citation statements)

References 9 publications

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“…26,27 In WAT of SHR, adrenergic nerve fibers are abundantly distributed not only around vessels but also directly on parenchymal cells, including adipocytes. 26 In addition, SHR are characterized by a deletion mutation of Cd36, 47,48 which is a fatty acid transporter that mediates fatty acids uptake by adipocytes (and other cells) and is involved in cold-induced brown fat thermogenesis. 49 Because of the deletion mutation, Cd36 is undetectable in SHR adipocyte plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

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High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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Obesity has a profound adverse impact on health. In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). We studied adult males fed a HFD or normal diet (ND) for 12 weeks. At the end of the 12-week dietary intervention, HFD compared with ND rats showed significantly higher whole-body energy expenditure. HFD vs. ND rats also showed higher expression of genes involved in fatty acid oxidation, mitochondrial biogenesis and brown fat adipogenesis, as well as augmented mitochondrial mass in WAT but not in the liver or skeletal muscle. Consistent with the molecular changes, in HFD but not in ND rats, histological and immunohistochemistry-based analyses of WAT demonstrated the presence of small multilocular cells staining positively for uncoupling protein 1, indicating the emergence of brown-like adipocytes in WAT. Our results suggest that SHR may have the capacity to increase energy expenditure in response to a chronic HFD that may be linked to the emergence of brown-like adipocytes in WAT. Thus, the SHR may be an important genetic model to uncover novel mechanisms of resistance to dietary obesity.

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Section: Discussionmentioning

confidence: 99%

“…49 Because of the deletion mutation, Cd36 is undetectable in SHR adipocyte plasma membrane. 47,48 Whether this genetic alteration has a role in the observed HFD-induced brown-fat emergence in WAT requires further studies, however.…”

Section: Discussionmentioning

confidence: 99%

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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“…These rats are hypertensive, insulin resistant and have impaired fatty acid uptake (Pravenec, et al, 1999). The CD36 mutation correlates best with the impaired fatty acid uptake phenotype, which then may affect insulin resistance in this model (especially given the expression of CD36 in liver) (Pravenec, et al, 1999,Collison, et al, 2000,Pravenec, et al, 2001,Hajri, et al, 2001,Zhang, et al, 2003. Indeed, work using CD36 KO mice showed secondary effects to decreased peripheral fatty acid uptake.…”

Section: Cd36 and Insulin Resistancementioning

confidence: 94%

CD36: Implications in cardiovascular disease

Febbraio

Silverstein

2007

The International Journal of Biochemistry & Cell Biology

213

215

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CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of gram positive bacterial walls and malaria infected erythrocytes. CD36 expression on macrophages, dendritic and endothelial cells, and in tissues including muscle, heart, and fat, suggest diverse roles, and indeed, this is truly a multifunctional receptor involved in both homeostatic and pathologic conditions. Despite an impressive increase in our knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This review focuses on CD36 in cardiovascular disease-what we know, and what we have yet to learn.

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“…Genes with a potential impact on lipid metabolism in this region include neuropeptide-Y (Npy) and fatty acid binding protein 1 (Fabp1) [14]. However, it is important to note that the Cd36 (Fat) gene in which a mutation has been shown to cause defective fatty acid and glucose metabolism in SHR [15,16] lies considerably away from the region containing our QTL. On rat chromosome 8, a QTL for plasma Tg at D8Mit2 in the Otsuka Long-Evans Tokushima Fatty rat has been reported [17].…”

Section: Discussionmentioning

confidence: 99%

Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome

et al. 2003

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Aims/hypothesis. Hypertriglyceridaemia is an important risk factor for coronary heart disease, especially in the context of the insulin resistance syndrome where it often occurs with hypertension. The two phenotypes are also associated in the hereditary hypertriglyceridaemic (hHTg) rat. The aim of this study was to map quantitative trait loci that affect plasma triglyceride concentration in the hHTg rat and determine whether they co-localize with loci for blood pressure. Methods. Second filial generation progeny (n=189) from a cross of the hHTg rat with the Brown Norway rat were phenotyped for fasting plasma triglyceride, glucose and insulin concentrations, and direct unrestrained resting blood pressure. A partial genome-scan was conducted using 153 microsatellite markers that were polymorphic between the two strains. Results. A major locus (lod score 6.5) influencing plasma triglyceride concentration in a co-dominant fashion was mapped to chromosome 4 between D1Mit5 and D1Mit17. Chromosome 8 contained multiple peaks with a lod score greater than 4.0 influencing triglyceride concentration. Importantly, none of the triglyceride loci had an effect on blood pressure. The triglyceride locus on chromosome 4 co-localized with a locus for fasting plasma insulin (lod score 4.1), although the effect on insulin concentration was in the opposite direction to that on triglyceride. Conclusion/interpretation. We have mapped the major loci that affect plasma triglyceride concentration in the hHTg rat. These loci do not influence blood pressure suggesting that these commonly associated phenotypes of the insulin resistance syndrome are not be due to pleiotropic effects of the same gene(s). [Diabetologia (2003) 46:352-358]

show abstract

Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats

Cited by 184 publications

References 9 publications

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

CD36: Implications in cardiovascular disease

Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome

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