Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking

Sandoval, Angel; Fraisl, Peter; Arias-Barrau, Elsa; DiRusso, Concetta C.; Singer, Diane; Sealls, Whitney; Black, Paul N.

doi:10.1016/j.abb.2008.06.010

Cited by 67 publications

(85 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the proteins reported to contribute to FFA uptake, FAT/CD36 has been associated with uptake in both adipocytes and cardiomyocytes (9,44,45). However, we found virtually identical transport characteristics in adipocytes, which express FAT/CD36, and preadipocytes, in which expression of FAT/CD36 is Ͻ5% that of adipocytes (12,13). Moreover, FFA transport characteristics we observed in cardiomyocytes obtained from FAT/CD36 Ϫ/Ϫ mice are largely similar to those from WT mice (Fig.…”

Section: Discussionmentioning

confidence: 44%

“…In previous studies of FFA transport we found virtually identical characteristics in adipocytes and preadipocytes, suggesting involvement of an unknown protein because FAT/ CD36, FABPpm, and FATP4 are expressed poorly or not at all in preadipocytes (2,(11)(12)(13). Transport in these studies was observed by imaging the concentration of intracellular unbound FFA (FFA i ) (11,12,14).…”

Section: From the Torrey Pines Institute For Molecular Studies San Dmentioning

confidence: 92%

See 1 more Smart Citation

Fatty Acid (FFA) Transport in Cardiomyocytes Revealed by Imaging Unbound FFA Is Mediated by an FFA Pump Modulated by the CD36 Protein

Carley

Kleinfeld

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Regulation of FFA 3 transport across the cardiomyocyte membrane is essential for cardiovascular health and dysregulation may result in myocardial lipotoxicity (1). However, the mechanisms governing FFA transport across cell membranes are not well understood (2, 3). Proposed mechanisms include rapid flip-flop through the lipid phase of the plasma membrane (4) or a protein-mediated mechanism (2, 3, 5). Proteins reported to be correlated with FFA transport in cardiac or muscle cells include FAT/CD36, FABPpm, and FATP4 (6 -10).In previous studies of FFA transport we found virtually identical characteristics in adipocytes and preadipocytes, suggesting involvement of an unknown protein because FAT/ CD36, FABPpm, and FATP4 are expressed poorly or not at all in preadipocytes (2, 11-13). Transport in these studies was observed by imaging the concentration of intracellular unbound FFA (FFA i ) (11,12,14). This allowed us to directly monitor the movement of unbound FFA (FFA u ) from the extracellular medium and into the cytosol.Because FFA transport plays a vital role in the heart and because our adipocyte/preadipocyte results raise the possibility that novel FFA transport mechanisms might exist in other tissues, we have investigated FFA transport in cardiomyocytes isolated from wild type (WT) adult C57BL/6 mice and FAT/ CD36 Ϫ/Ϫ mice on the C57BL/6 background. We used several methods to monitor FFA transport in this study, so that key findings were confirmed independently of a specific method. These methods included 1) quantitative imaging of FFA i using a sensor of FFA, ADIFAB (acrylodan-labeled rat intestinal fatty acid-binding protein), 2) using the pH indicator BCECF-AM (2Ј,7Ј-bis(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester) to monitor FFA influx and efflux, and 3) a new method to determine FFA uptake by monitoring the extracellular unbound FFA concentration (FFA o ) using ADIFAB in the extracellular medium.This study provides the first measurements of FFA i in cardiac cells and the first direct measurements of FFA influx and efflux across the cardiac plasma membrane. The results suggest that FFAs are pumped into cardiomyocytes and that FAT/CD36 interacts with the transporter/pump so that it significantly modifies the rate of efflux and, to a lesser extent, the rate of influx. The results significantly alter current views of the mechanisms of FFA transport in cardiac myocytes and may provide insights for understanding the role of FFA in cardiac dysregulation. EXPERIMENTAL PROCEDURES

show abstract

Section: Discussionmentioning

confidence: 44%

Section: From the Torrey Pines Institute For Molecular Studies San Dmentioning

confidence: 92%

Fatty Acid (FFA) Transport in Cardiomyocytes Revealed by Imaging Unbound FFA Is Mediated by an FFA Pump Modulated by the CD36 Protein

Carley

Kleinfeld

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…FATP2 is expressed primarily in liver and kidney (183,191,226,366) as well as in the intestines (190), whereas FATP3 has a more restricted distribution being expressed in liver, lung, testis, and skin (191,328,375). FATP4 is expressed in intestine, brain, kidney, liver, skin, lung, heart, and skeletal muscle (107, 153, 181, 185-187, 191, 219, 315, 375).…”

Section: Fatty Acid Transport Proteinsmentioning

confidence: 99%

Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease

Glatz

Luiken

Bonen

2010

Physiological Reviews

627

662

View full text Add to dashboard Cite

Long-chain fatty acids and lipids serve a wide variety of functions in mammalian homeostasis, particularly in the formation and dynamic properties of biological membranes and as fuels for energy production in tissues such as heart and skeletal muscle. On the other hand, long-chain fatty acid metabolites may exert toxic effects on cellular functions and cause cell injury. Therefore, fatty acid uptake into the cell and intracellular handling need to be carefully controlled. In the last few years, our knowledge of the regulation of cellular fatty acid uptake has dramatically increased. Notably, fatty acid uptake was found to occur by a mechanism that resembles that of cellular glucose uptake. Thus, following an acute stimulus, particularly insulin or muscle contraction, specific fatty acid transporters translocate from intracellular stores to the plasma membrane to facilitate fatty acid uptake, just as these same stimuli recruit glucose transporters to increase glucose uptake. This regulatory mechanism is important to clear lipids from the circulation postprandially and to rapidly facilitate substrate provision when the metabolic demands of heart and muscle are increased by contractile activity. Studies in both humans and animal models have implicated fatty acid transporters in the pathogenesis of diseases such as the progression of obesity to insulin resistance and type 2 diabetes. As a result, membrane fatty acid transporters are now being regarded as a promising therapeutic target to redirect lipid fluxes in the body in an organ-specific fashion.

show abstract

“…Assays were conducted in the presence of the quenching agent trypan blue, as described elsewhere (40). After excitation at 490 nm, fluorescence at 520 nm was determined using a fluorescent plate reader.…”

Section: Bodipy Assaymentioning

confidence: 99%

Increased Mitochondrial Activity in BMP7-Treated Brown Adipocytes, Due to Increased CPT1- and CD36-Mediated Fatty Acid Uptake

Townsend

Ding

Lynes

et al. 2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Aims: Brown adipose tissue dissipates chemical energy in the form of heat and regulates triglyceride and glucose metabolism in the body. Factors that regulate fatty acid uptake and oxidation in brown adipocytes have not yet been fully elucidated. Bone morphogenetic protein 7 (BMP7) is a growth factor capable of inducing brown fat mitochondrial biogenesis during differentiation from adipocyte progenitors. Administration of BMP7 to mice also results in increased energy expenditure. To determine if BMP7 is able to affect the mitochondrial activity of mature brown adipocytes, independent of the differentiation process, we delivered BMP7 to mature brown adipocytes and measured mitochondrial activity. Results: We found that BMP7 increased mitochondrial activity, including fatty acid oxidation and citrate synthase activity, without increasing the mitochondrial number. This was accompanied by an increase in fatty acid uptake and increased protein expression of CPT1 and CD36, which import fatty acids into the mitochondria and the cell, respectively. Importantly, inhibition of either CPT1 or CD36 resulted in a blunting of the mitochondrial activity of BMP7-treated cells. Innovation: These findings uncover a novel pathway regulating mitochondrial activities in mature brown adipocytes by BMP7-mediated fatty acid uptake and oxidation. Conclusion: In conclusion, BMP7 increases mitochondrial activity in mature brown adipocytes via increased fatty acid uptake and oxidation, a process that requires the fatty acid transporters CPT1 and CD36. Antioxid. Redox Signal. 19,[243][244][245][246][247][248][249][250][251][252][253][254][255][256][257]

show abstract

Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking

Cited by 67 publications

References 38 publications

Fatty Acid (FFA) Transport in Cardiomyocytes Revealed by Imaging Unbound FFA Is Mediated by an FFA Pump Modulated by the CD36 Protein

Fatty Acid (FFA) Transport in Cardiomyocytes Revealed by Imaging Unbound FFA Is Mediated by an FFA Pump Modulated by the CD36 Protein

Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease

Increased Mitochondrial Activity in BMP7-Treated Brown Adipocytes, Due to Increased CPT1- and CD36-Mediated Fatty Acid Uptake

Contact Info

Product

Resources

About