Edited by Dennis R. VoelkerAcyl-CoA binding domain-containing 5 (ACBD5) is a peroxisomal protein that carries an acyl-CoA binding domain (ACBD) at its N-terminal region. The recent identification of a mutation in the ACBD5 gene in patients with a syndromic form of retinal dystrophy highlights the physiological importance of ACBD5 in humans. However, the underlying pathogenic mechanisms and the precise function of ACBD5 remain unclear. We herein report that ACBD5 is a peroxisomal tail-anchored membrane protein exposing its ACBD to the cytosol. Using patient-derived fibroblasts and ACBD5 knock-out HeLa cells generated via genome editing, we demonstrate that ACBD5 deficiency causes a moderate but significant defect in peroxisomal ␤-oxidation of very-long-chain fatty acids (VLCFAs) and elevates the level of cellular phospholipids containing VLCFAs without affecting peroxisome biogenesis, including the import of membrane and matrix proteins. Both the N-terminal ACBD and peroxisomal localization of ACBD5 are prerequisite for efficient VLCFA ␤-oxidation in peroxisomes. Furthermore, ACBD5 preferentially binds very-long-chain fatty acyl-CoAs (VLC-CoAs). Together, these results suggest a direct role of ACBD5 in peroxisomal VLCFA ␤-oxidation. Based on our findings, we propose that ACBD5 captures VLC-CoAs on the cytosolic side of the peroxisomal membrane so that the transport of VLC-CoAs into peroxisomes and subsequent ␤-oxidation thereof can proceed efficiently. Our study reclassifies ACBD5-related phenotype as a novel peroxisomal disorder.

Background: Little is known as to the associations between childhood obesity and chronic low-grade inflammation, circulatory, hepatic, metabolic and haematological abnormalities. Methods and Results: A total of 1,871 boys and 1,810 girls were measured anthropometric data, white blood cell (WBCC), platelet count, blood pressure, plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and highdensity (HDL) lipoprotein cholesterol,. The subjects were classified into three body mass index categories depending on the international standard definition for child overweight and obesity. WBCC, platelet counts, systolic blood pressure, serum levels of aminotransferases,TG and HDL-cholesterol were related with body composition in both boys and girls. Obese girls had high risks of having abnormal levels of WBCC, platelet count, systolic blood pressure (SBP), ALT, TG, HDL-cholesterol. Obese boys had high risks of having abnormal levels of WBCC, haemobobin concentration, platelet count, SBP, diastolic blood pressure, AST, ALT, TG, and HDL-cholesterol. Conclusions: Childhood obesity is related with chronic inflammation, hypercoagulability, as well as circulatory, metabolic, and hepatic abnormalities.

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