Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes

Caserta, Frank; Tchkonia, Tamara; Civelek, Vildan N.; Prentki, Marc; Brown, Nicholas F.; McGarry, Julie; Forse, R. Armour; Corkey, Barbara E.; Hamilton, James A.; Kirkland, James L.

doi:10.1152/ajpendo.2001.280.2.e238

Cited by 73 publications

(66 citation statements)

References 88 publications

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“…On the basis of these properties in model membranes, the diffusion mechanism can be considered a viable mechanism for transport of FA across cell membranes (16,25,29,37). We also extended our measurements of the transmembrane movement of FA to cells with a trapped pH dye (BCECF), both in suspension (38,40), and as single cells (41). Decreases in cytosolic pH occurred immediately after the addition of FA to the external medium, supporting the hypothesis that FA diffuse across the plasma membrane by the flip-flop mechanism.…”

supporting

confidence: 64%

Rapid Flip-flop of Oleic Acid across the Plasma Membrane of Adipocytes

Kamp

Guo

Souto

et al. 2003

Journal of Biological Chemistry

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113

111

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Nonesterified long-chain fatty acids may enter cells by free diffusion or by membrane protein transporters. A requirement for proteins to transport fatty acids across the plasma membrane would imply low partitioning of fatty acids into the membrane lipids, and/or a slower rate of diffusion (flip-flop) through the lipid domains compared to the rates of intracellular metabolism of fatty acids. We used both vesicles of the plasma membrane of adipocytes and intact adipocytes to study transmembrane fluxes of externally added oleic acid at concentrations below its solubility limit at pH 7.4. Binding of oleic acid to the plasma membrane was determined by measuring the fluorescent fatty acid-binding protein ADIFAB added to the external medium. Changes in internal pH caused by flip-flop and metabolism were measured by trapping a fluorescent pH indicator in the cells. The metabolic end products of oleic acid were evaluated over the time interval required for the return of intracellular pH to its initial value. The primary findings were that (i) oleic acid rapidly binds with high avidity in the lipid domains of the plasma membrane with an apparent partition coefficient similar to that of protein-free phospholipid bilayers; (ii) oleic acid rapidly crosses the plasma membrane by the flip-flop mechanism (both events occur within 5 s); and (iii) the kinetics of esterification of oleic acid closely follow the time dependence of the recovery of intracellular pH. Any postulated transport mechanism for facilitating translocation of fatty acid across the plasma membrane of adipocytes, including a protein transporter, would have to compete with the highly effective flip-flop mechanism.Adipocytes are highly differentiated cells specialized in handling large quantities of un-esterified long-chain fatty acids (FA).1 During lipid storage in the fed state, FA are released in the blood from chylomicrons by lipolysis or from albumin, move through the endothelium, bind to the outer leaflet of the plasma membrane, and cross the membrane bilayer. FA are trapped in the cytoplasm by conversion to acyl-CoA and stored primarily as triglycerides in lipid droplets (reviewed in Glatz et al. (1)). During lipolysis of stored triglycerides in the fasting state, FA are released from intracellular lipid droplets, move to and cross the plasma membrane, and are released into the interstitial space, where they bind to albumin. Subsequently, the FA pass through the endothelial cells or diffuse through the spaces between them to reach the blood. These large bidirectional fluxes could occur by several postulated mechanisms, both complex and simple. Cytological changes observed in adipocytes during release and deposition of intracellular lipid led to the complex model that large intracellular fluxes of FA occur by formation of vesicles from the plasma membrane of adipocytes and endothelial cells (2, 3). It has also been postulated that caveolin, a protein present in invaginations of the plasma membrane (caveolae), plays a role in FA uptake (4). There are severa...

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supporting

confidence: 64%

Rapid Flip-flop of Oleic Acid across the Plasma Membrane of Adipocytes

Kamp

Guo

Souto

et al. 2003

Journal of Biological Chemistry

Self Cite

113

111

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“…Furthermore, adipose tissue has the potential to be a source of cells for tissue engineer purposes, as it appears to contain cells able to act as functional and vascular building blocks for several tissues (Fraser et al, 2006). The potential for cellular development of adipocytes is believed to be fixed relatively early in life, with changes thereafter in either the size or number of cells that occur in proportion to the initial cell number and lipogenic proteins (Caserta et al, 2001;Pethick et al, 2004;Wang et al, 2009). Moreover, dysfunction of the adipose compartment (cells and metabolism) is central to the pathology associated with metabolic diseases such as obesity, type II diabetes (Edelman, 1998), cancer cachexia and lipodystrophies (Cristancho and Lazar, 2011).…”

Section: Introductionmentioning

confidence: 99%

Review: Animal model and the current understanding of molecule dynamics of adipogenesis

Campos

Duarte

Guimarães

et al. 2016

Animal

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Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.

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“…From a nutritional perspective, the deposition of IMF has a strong impact on nutritional and technological properties of swine meat (Wood et al, 2008). It is well known that the development of adipocytes is fixed relatively early in life and that subsequent processing affecting both size and number occurs in proportion to the initial cell number and lipogenic proteins (Caserta et al, 2001;Pethick et al, 2004). Therefore, to improve IMF, the first and foremost approach is to determine a genetically based method for accumulating more adipocytes in muscle.…”

Section: Introductionmentioning

confidence: 99%