Abstract
Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m², age 23-33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = -0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans.
Highlights
Animal studies have suggested that angiopoietinlike 4 (Angptl4) regulates adiposity through central and peripheral mechanisms
We studied the relationship between Angptl4 and fibroblast growth factor 21 (FGF21), a fasting-induced hormone that shares similarities in gene regulation [21,22,23] and has been reported to correlate with s-Angptl4 levels [24], as well as Angptl3, a structurally related protein that does not correlate with s-Angptl4 levels [13]
In the whole-study population, s-Angptl4 levels were significantly correlated only with serum free fatty acid (FFA) (r = 0.15, P = 0.01), and this correlation was independent of gender, zygosity, or body mass index (BMI)
Summary
Animal studies have suggested that angiopoietinlike 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl are associated with obesity-related parameters in humans. Serum Angptl (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. Intra-pair differences in s-Angptl levels were inversely correlated with intra-pair differences in BMI (r = ؊0.27, P = 0.003). Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins.
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