CD36 Protein Influences Myocardial Ca2+ Homeostasis and Phospholipid Metabolism

Pietka, Terri; Sulkin, Matthew S.; Kuda, Ondřej; Wang, Wei; Zhou, Dequan; Yamada, Kathryn A.; Yang, Kui; Su, Xiong; Gross, Richard W.; Nerbonne, Jeanne M.; Efimov, Igor R.; Abumrad, Nada A.

doi:10.1074/jbc.m112.413609

Cited by 27 publications

(34 citation statements)

References 75 publications

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“…Enhanced phospholipid deacylation associates with VLDL production and might be important for sorting the lipid to the secretory pool and/or for VLDL particle maturation (45)(46)(47). CD36-mediated signaling infl uences phospholipase activation and phospholipid remodeling ( 19,20,48 ), resulting in the generation of PG, with additional effects on ionic fl ux and lipid turnover ( 49,50 ). Thus CD36 expression in the liver might play dual roles: facilitating FA fl ux under conditions of high FA supply ( 11,12 ) and transducing intracellular signals that regulate phospholipid deacylation and eicosanoid production, events that would infl uence assembly and secretion of VLDL particles.…”

Section: Discussionmentioning

confidence: 99%

“…Recent data documented the role of CD36-mediated signaling in FA metabolism via affecting cellular calcium ( 18,19 ) and the MAPK ERK1/2 pathway ( 20,21 ). An important consequence of CD36's ability to signal to intracellular calcium was its regulation of the formation and release of prostaglandins (PG) ( 20 ), bioactive compounds with pleiotropic effects that include inhibition of hepatic VLDL secretion ( 22,23 ).…”

Section: Hepatic Triglyceride and Apob Secretion And Microsomal Triglmentioning

confidence: 99%

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CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

Nassir

Adewole

Brunt

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org novo FA synthesis or de novo lipogenesis (DNL), decreased FA oxidation, and reduced secretion of VLDLs ( 1, 2 ).CD36 is a class B scavenger receptor that plays an important role in several pathways of FA utilization. The protein is expressed in many cell types, including lingual taste bud cells, enterocytes, adipocytes, myocytes, and immune cells. On taste bud cells, CD36 is important for FA recognition and fat perception ( 3, 4 ). In skeletal muscle, heart, and adipose tissue, CD36 facilitates tissue FA uptake and utilization ( 5, 6 ). In the small intestine, it is important for chylomicron secretion ( 7 ) and for FA-induced release of secretin and cholecystokinin ( 8 ). In the liver, CD36 is expressed on endothelial, parenchymal, and Kupffer cells ( 9 ). Basal expression of liver CD36 is low but increases in experimental models of hepatic steatosis, such as genetic obesity and highfat feeding ( 10, 11 ) or following activation of the prosteatotic transcription factors liver X receptor (LXR), pregnane X receptor (PXR), and aryl hydrocarbon receptor (AHR) by xenobiotics, bacteria, or cytokines ( 12 ). Mice fed a highfat diet have increased liver CD36 expression associated with enhanced hepatic FA uptake and TG accumulation, and these are prevented by CD36 deletion ( 11 ). Interestingly, however, the prosteatotic effects of a high-fructose diet, which enhances DNL and TG accumulation in the liver ( 13 ), are exacerbated by CD36 deletion ( 14 ).In humans with nonalcoholic fatty liver disease (NAFLD), hepatic CD36 positively correlates with liver fat content ( 15 ), but its relationship to output of VLDL suggests that its impact on hepatic FA metabolism might not be limited to enhancing FA fl ux and TG accumulation. NAFLD is Abstract Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was reduced in vitro using incubated liver slices. The effect of CD36 deletion was mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2. Treatment of CD36-defi cient slices with inhibitors of cyclooxygenases reversed the reduction in triglyceride secretion. We also examined the effect of CD36 deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 ( ob-CD36 ؊ / ؊ ) were generated and studied for hepatic triglyceride accumulation and VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the steatosis by impairing hepatic triglyceride and apoB secretion through increasing prostaglandin levels. These fi ndings suggest an unappreciated role of CD36 in reg...

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Section: Discussionmentioning

confidence: 99%

Section: Hepatic Triglyceride and Apob Secretion And Microsomal Triglmentioning

confidence: 99%

CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

Nassir

Adewole

Brunt

et al. 2013

Journal of Lipid Research

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“…CD36 regulation of cytosolic Ca ++ can be dependent (19, 22, 90) or independent (43, 73) of direct FA interaction with CD36. Increases in free cytoplasmic Ca ++ induced by the binding of an extracellular ligand to its surface receptor are a major cellular route for information relay and usually involve the release of stored calcium coupled with calcium influx across the plasma membrane.…”

Section: Cd36 Signaling Coordinates Fat Metabolismmentioning

confidence: 99%

Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

et al. 2014

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CD36 is a scavenger receptor that functions in high affinity tissue uptake of long chain fatty acids (FA) and contributes under excessive fat supply to lipid accumulation and metabolic dysfunction. This review describes recent evidence regarding the CD36 FA binding site and a potential mechanism for FA transfer. It also presents the view that CD36 and FA signaling coordinate fat utilization based on newly identified CD36 actions that involve oral fat perception, intestinal fat absorption, secretion of the peptides cholecystokinin and secretin, regulation of hepatic lipoprotein output, activation of beta oxidation by muscle and regulation of the production of the FA derived bioactive eicosanoids. Thus abnormalities of fat metabolism and the associated pathology might involve dysfunction of CD36-mediated signal transduction in addition to the changes of FA uptake.

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“…Figure 2A shows the digital design and printed chamber for a vertical Langendorff-perfused mouse heart, where optical imaging is done through the side glass window. Unlike imaging a horizontally oriented heart from the surface (5), optical mapping of a vertically submerged preparation reduces artifact of the rippling fluid created by a superfusion pump (9). Figure 2B displays two examples of electrode holders that slide over the columns of the tissue restrainer (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Optical mapping of transmembrane potential (V m) and calcium transients (CaT) was done as previously described (5,9). Briefly, tissue was stained with voltagesensitive dye (RH-237; 5 l in 1 mg/ml DMSO; Life Technologies, Carlsbad, CA) and immobilized by addition of blebbistatin (10 M; Tocris Bioscience, Ellisville, MO) to reduce motion artifact.…”

Section: Methodsmentioning

confidence: 99%

Three-dimensional printing physiology laboratory technology

Sulkin

Widder

Shao

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Since its inception in 19th-century Germany, the physiology laboratory has been a complex and expensive research enterprise involving experts in various fields of science and engineering. Physiology research has been critically dependent on cutting-edge technological support of mechanical, electrical, optical, and more recently computer engineers. Evolution of modern experimental equipment is constrained by lack of direct communication between the physiological community and industry producing this equipment. Fortunately, recent advances in open source technologies, including three-dimensional printing, open source hardware and software, present an exciting opportunity to bring the design and development of research instrumentation to the end user, i.e., life scientists. Here we provide an overview on how to develop customized, cost-effective experimental equipment for physiology laboratories.

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CD36 Protein Influences Myocardial Ca2+ Homeostasis and Phospholipid Metabolism

Abstract: Background: Myocardial function during fasting was examined in wild-type and CD36Ϫ/Ϫ mice.

Cited by 27 publications

References 75 publications

CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

Three-dimensional printing physiology laboratory technology

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