Medicinal chemistry Ali and Ranneh, Med chem 2013, 3:4 http://dx.doi.org/10.4172/2161-0444.1000151 Research Article Open Access Med chem ISSN: 2161-0444 Med chem, an open access journal Volume 3(4): 276-281 (2013) - 276 Angiopoietin-like Protein 4 and the level of Free Fatty Acids in Human Blood Plasma: Is there a link? Faisal H H Ali 1,2 * and Yazan Ranneh 1 1 Department of Nutrition and Dietetics, Faculty of medicine and health sciences, Nutrigenomics Programme, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia 2 Metabolism and genomics group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands Abstract Background: Angiopoietin-like protein 4 (Angptl4) is a new circulating protein of the Angiopoietin-like family, predominantly expressed in adipose tissue and liver. A link between Angptl4 and the levels of free fatty acids in human blood plasma remains unclear. Therefore, we hypothesized that any alteration in the concentration of plasma Angptl4 may be mediated by changes in plasma free fatty acid levels in healthy individuals. Methods: To examine the effect of plasma free fatty acid levels on Angptl4 concentrations in humans, ELISA method was developed and used for the quantitative determination of human Angptl4 in plasma samples with known free fatty acid concentrations. Results: It was clearly observed that there were signiicant (P. value<0.01) positive correlation between plasma Angptl4 concentrations and plasma levels of free fatty acid (0.905 ≤ r ≤ 1.00) and the standard curve using the human recombinant Angptl4 fragments yielded a consistent r 2 value>0.993. Raising plasma fatty acids resulted in an increase in the levels of Angptl4. While, lowering plasma fatty acids resulted in a decrease in the levels of Angptl4. Conclusion: The results of this study indicate that changes in plasma free fatty acid levels are associated with alterations in the concentrations of Angptl4. *Corresponding author: Faisal H H Ali, Metabolism and genomics group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands, Tel: +60389472435, Fax: +60389426769; E-mail: sshrmany@yahoo.co.uk Received September 05, 2013; Accepted September 27, 2013; Published September 30, 2013 Citation: Ali FHH, Ranneh Y (2013) Angiopoietin-like Protein 4 and the level of Free Fatty Acids in Human Blood Plasma: Is there a link? Med chem 3: 276-281. doi:10.4172/2161-0444.1000151 Copyright: © 2013 Ali FHH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: Angptl4; FFAs; Human blood plasma; ELISA; Dyslipidemia Introduction Dyslipidemia (abnormality of lipid metabolism) is the major risk factor of metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus [1]. It is characterized by elevated level of plasma triglyceride (TG), increased levels of low-density lipoprotein (LDL), and decreased high-density lipoprotein cholesterol (HDL-C). Furthermore, high plasma TG also called hypertriglyceridemia is the major health problems in the world and afecting about 47 million (24%) of the U.S adult population [2]. So, efective therapeutic approaches to combat it are currently of interest. More recently, a family of proteins structurally similar to the angiogenic regulating factors angiopoietins has been identiied and designated “angiopoietin-like proteins” (Angptls) or angiopoietin-related proteins. Several studies in mice show that Angptls family proteins play an important role in the regulation of plasma lipid, and energy metabolism independently of angiogenic efects [3-8]. Angiopoietin-like 4 (Angptl4) is one of the recently secreted Angptls with a predicted molecular weight of approximately 50 kDa that belongs to the angiopoietin family and is involved in angiogenesis and metabolism regulation [9-13]. Angptl4 was discovered by three diferent groups at the same year by diferent names, e.g., PGAR [peroxisome proliferator-activated receptor γ (PPAR γ) angiopoietin related], FIAF (fasting-induced adipose factor), or HFARP (hepatic ibrinogen/ angiopoietin-related protein) [14-16]. A number of studies reported that Angptl4 protein can be detected in various mouse and human tissues where it is produced as well as in mouse and human blood plasma [15,17]. In addition, the metabolic role of Angptl4 has been extensively studied in a variety of tissues particularly in mice. Indeed, it has been reported that Angptl4 plays an important role in the regulation of lipoprotein metabolism, adiposity both in vivo and in vitro. Furthermore, subsequent studies in mice have been shown that Angptl4 potently elevates triglycerides-rich lipoprotein in plasma [10,17-23]. In pathophysiology, elevated plasma fatty acids concentrations are associated with metabolic syndrome and its accompanying disorders such as diabetes and obesity [1,2]. In normal state, high fatty acid concentrations in plasma are highly connected with prolonged fasting and exercise [24]. Non etseriied fatty acids (NEFAs) or free fatty acids (FFAs) are derived from either lipolysis of adipose tissue TG or chylomicrons of dietary fat [24-26]. Currently, it has become increasingly clear from the collective data using experimental animals that Angptl4 plays an important role in the regulation of free fatty acids concentration in blood plasma via stimulating adipose tissue lipolysis [4,5,17]. Importantly, functional tests indicated that Angptl4 Prevents the clearance of triglycerides from the TG-rich lipoproteins VLDL and chylomicrons, most likely by inhibiting lipoprotein lipase, a key regulatory enzyme in fatty acid metabolism that is synthesized mainly in muscle and adipose tissue. Decreased LPL activity leads to higher plasma TG levels and thereby, increases of TG lipolysis in adipose tissue into free fatty acids and glycerol [10-12]. Rising in plasma FFAs in transgenic mice can be explained by adipose tissue lipolysis and thereby prevent fat storage and stimulate the mobilization of adipose TGs. For this reason Angptl4 has been considered as a new modulator of plasma FFAs level in mice [5,8]. However, in human, the physiological and nutritional role of the later regulation remains unclear. Interestingly, the genetic evidence has