The role of apolipoprotein A5 in obesity and the metabolic syndrome

Abstract

Apolipoprotein A5 (apoA5) has an important role in lipid metabolism, specifically for triglyceride-rich lipoproteins. Recently, evidence has emerged for an association between genetic variability at the APOA5 locus and increased risk of obesity and metabolic syndrome. However, its mechanism of action remains to be fully elucidated. Importantly, an intracellular role of apoA5 has been indicated since apoA5 is associated with cytoplasmic lipid droplets and affects intrahepatic triglyceride accumulation, as well as affecting intravascular triglyceride metabolism. Given that adipocytes provide the largest storage depot for energy in the form of triglyceride within the lipid droplets, and play a crucial role in the development of obesity, we highlight recent findings discussing the interaction of apoA5 with adipocytes or adipose tissue, indicating that apoA5 may act as a novel regulator to modulate triglyceride storage in adipocytes. We review the association of APOA5 gene polymorphisms with obesity and metabolic syndrome, and propose potential mechanisms by which apoA5 may increase susceptibility to these conditions. This review provides new insights into the physiological role of apoA5 and identifies a potential therapeutic target for obesity and associated disorders.

Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population

“…The association of the rare allele of both SNPs with increased triglyceride levels was also demonstrated in other studies [26,28,30e32]. Zheng at al [33]. observed that most of the studies evaluating the association of APOA5 SNPs with metabolic syndrome or its components lacked the correction for triglyceride levels or that the association disappeared after this correction.…”

Association of rs662799 variant and APOA5 gene haplotypes with metabolic syndrome and its components: a meta-analysis in North Africa

“…Rs662799 was strongly associated with MetS OR = 3.622 (1.2-10.936) p = 0.02 for the Hungarian population [21]. The minor C allele of this SNP was associated with an approximately 50% higher risk of MetS in Chinese population [30]; and for the Greek population a strong correlation was also found OR = 3.514 (1.065-11.585) p = 0.035 [31]. In addition a metanalysis study performed with 13863 individuals from Europe, Asia, and Latin America reported that the carrier of the rs662799 C allele had a 33% increased risk of developing MetS [32].…”

Single-nucleotide polymorphisms and DNA methylation markers associated with central obesity and regulation of body weight

“…The most significant association with a central adiposity measurement was that between the variant rs2266788 in APOA5 and waist circumference‐triglycerides. APOA5 encodes a protein found in chylomicrons, which regulates the plasma triglyceride levels, as well as very low‐density lipoprotein and HDLc . The CETP gene, associated with the binary trait HDLc‐waist circumference, has a functional role in the transfer of cholesterol esters between lipoproteins.…”