Fatty acid uptake

PPARy is strongly expressed in adipocytes, and stimulation by TZDs promotes adipogenesis, predominantly in preadipocytes from subcutaneous depots. Increased transcription of transporters and enzymes involved in fatty acid uptake and lipogenesis increases the deposition of lipid in these adipocytes (Table 2). This appears to facilitate a reduction in hyperglycaemia by reducing circulating concentrations of non-esterified... 

Biological actions Adipocyte differentiation fatty acid uptake lipogenesis glucose uptake other effects on nutrient metabolism which lower hepatic glucose production... 

Uptake of LCFAs across the lipid-bilayer of most mammalian cells occurs through both a passive diffusion of LCFAs and a protein-mediated LCFA uptake mechanism. At physiological LCFA concentrations (7.5 nM) the protein-mediated, saturable, substrate-specific, and hormonally regulated mechanism of fatty acids accounts for the majority (>90%) of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle, adipose tissue, liver,... 

Fatty Acid Transporters. Figure 2 Quencher-based real-time fatty acid uptake assay with a fluorescently labeled FFA analogue (C1-Bodipy-C12). Predominantly protein-mediated fatty acid uptake by 3T3-L1 adipocytes (diamonds) was compared with diffusion-driven uptake by fibroblasts (squares) using the QBT Fatty Acid Uptake reagent (Molecular Devices Corp., CA, USA), which contains C1-Bodipy-C12 as substrate in conjunction with a cell impermeable quencher. Uptake kinetics was recorded using a Gemini fluorescence plate reader. Error bars indicate the standard deviations from 12 independent wells. RFU relative fluorescence units. 

In vitro and ex vivo studies have shown that FATPs transport LCFAs and very long-chain fatty acids (VLCFAs) but no medium-chain fatty acids, fatty acid esters, or lipid-soluble vitamins [4]. LCFA transport is inhibited by prior protease treatment. Synthetic substrates for FATPs include 14C-labeled fatty acids and the fluorescently labeled fatty acid analogue C1 -BODEP Y-Cl 2. Using the latter substrate, differences in fatty acid uptake kinetics between FATP expressing 3T3 LI adipocytes and 3T3 LI fibroblasts, which are devoid of FATPs, can be readily appreciated (Fig. 2). 

Knockout mice have been reported for several FATPs [1]. As insulin desensitization has been closely linked to excessive fatty acid uptake and intracellular diacylgly-cerol and TG accumulation, these animal models were particularly evaluated in the context of protection from diet-induced type 2 diabetes ( Type 2 Diabetes Mellitus (T2DM)). In addition, studies on human subjects have also established genetic links between polymorphisms in FATP genes and metabolic alterations [1]. 

Liver t Fatty acid uptake into hepatocytes l VLDL production... 

After uptake by the liver, free fatty acids are either P Oxidized to COj or ketone bodies or esterified to triacylglycerol and phospholipid. There is regulation of entry of fatty acids into the oxidative pathway by carnitine palmitojdtransferase-I (CPT-I), and the remainder of the fatty acid uptake is esterified. CPT-I activity is... 

Triacylglycerols must be hydrolyzed by a lipase to their constiment fatty acids and glycerol before further catab-ohsm can proceed. Much of this hydrolysis (hpolysis) occurs in adipose tissue with release of free fatty acids into the plasma, where they are found combined with semm albumin. This is followed by free fatty acid uptake into tissues (including hver, heart, kidney, muscle, lung, testis, and adipose tissue, but not readily by brain), where they are oxidized or reesterified. The uti-hzation of glycerol depends upon whether such tissues... 

The free fatty acid uptake by tissues is related directly to the plasma free fatty acid concentration, which in turn is determined by the rate of lipolysis in adipose tissue. After dissociation of the fatty acid-albumin complex at the plasma membrane, fatty acids bind to a membrane tty acid transport protein that acts as a transmembrane cotransporter with Na. On entering the cytosol, free fatty acids are bound by intracellular fatty acid-binding proteins. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids. 

Trotter, P. J. et al. (1996). Fatty acid uptake by Caco-2 human intestinal cells. J. Lipid Res. 37(2) 336-346. 

Abumrad, N., C. Coburn, and A. Ibrahimi. Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells CD36, FATP and FABPm. Biochim. Biophys. Acta 1999, 3443, 4-13. 

Trotter, P.J. and Storch, J., Fatty acid uptake and metabolism in a human intestinal cell line (Caco-2) comparison of apical and basolateral incubation, /. Lipid Res., 32, 293,1991. 

M.T. Maki, M. Haaparanta, P. Nuutila, V. Oikonen, M. Luotolahti, O. Eskola, J.M. Knuuti, Free fatty acid uptake in the myocardium and skeletal muscle using fluorine-18-fluoro-6-thia heptadecanoic acid, J. Nucl. Med. 39 (1998) 1320-1327. 

H. Tuunanen, J. Kuusisto, J. Toikka, P. Jaaskelainen, P. Maijamaki, K. Peuhkurinen, T. Viljanen, P. Sipola, K.Q. Stolen, J. Hannukainen, P. Nuutila, M. Laakso, J. Knuuti, Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene A positron emission tomography study, J. Nucl. Cardiol. 14(2007) 354-365. 

The hormone adiponectin stimulates fatty acid uptake and oxidation and inhibits fatty acid synthesis. Its actions are mediated by AMPK. 

In addition to the longitudinal pH gradient, there is a pH gradient starting with the lumen to the absorbing surface [109,110]. Because of this gradient, the pH at the mucosal surface of the small intestine is different from that of the luminal content (a decrease of at least 1 pH unit, e.g., from 7.1 to 6.1) [111,112]. It was shown that the acidic microclimate is an essential determinant in fatty acid uptake after micellization [113]. The presence of a low-pH compartment facilitates the dissociation of mixed micelles made up of taurocholate and oleic acid. The rate of fatty acid diffusion in the mucin layer was estimated to be 400% of that in a buffer solution [114]. 

Shiau, Y.F. 1990. Mechanism of intestinal fatty acid uptake in the rat The role of an acidic microclimate. J Physiol 421 463. 

Kerkhoff C, Sorg C, Tandon NN, Nacken W. 2001. Interaction of S100A8/S100A9-arachidonic acid complexes with the scavenger receptor CD36 may facilitate fatty acid uptake by endothelial cells. Biochemistry 40(l) 241-248. 

Schurer, N.Y., Stremmel, W., Grundmann, J.-U. et al., Evidence for a novel keratinocyte fatty acid uptake mechanism with preference for linoleic acid comparison of oleic and linoleic acid uptake by... 

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