Beta-Carotene Reduces Body Adiposity of Mice via BCMO1

Evidence from cell culture studies indicates that β-carotene-(BC)-derived apocarotenoid signaling molecules can modulate the activities of nuclear receptors that regulate many aspects of adipocyte physiology. Two BC metabolizing enzymes, the BC-15,15′-oxygenase (Bcmo1) and the BC-9′,10′-oxygenase (Bcdo2) are expressed in adipocytes. Bcmo1 catalyzes the conversion of BC into retinaldehyde and Bcdo2 into β-10′-apocarotenal and β-ionone. Here we analyzed the impact of BC on body adiposity of mice. To genetically dissect the roles of Bcmo1 and Bcdo2 in this process, we used wild-type and Bcmo1-/- mice for this study. In wild-type mice, BC was converted into retinoids. In contrast, Bcmo1-/- mice showed increased expression of Bcdo2 in adipocytes and β-10′-apocarotenol accumulated as the major BC derivative. In wild-type mice, BC significantly reduced body adiposity (by 28%), leptinemia and adipocyte size. Genome wide microarray analysis of inguinal white adipose tissue revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. Despite β-10′-apocarotenoid production, this effect of BC was absent in Bcmo1-/- mice, demonstrating that it was dependent on the Bcmo1-mediated production of retinoids. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARγ activity in adipocyte

Improved resistance to serum oxidation in Gilbert's Syndrome: a mechanism for cardiovascular protection

Bilirubin is a potent antioxidant, however, uncertainty surrounds its physiological importance. Individuals with Gilbert’s syndrome (GS)have increased circulating bilirubin and a reduced prevalence of cardiovascular disease (CVD). The aim of this study was to investigate mechanisms that may link bilirubin to protection from CVD seen in GS by examining markers of antioxidant and oxidative stress status and the susceptibility of serum to oxidation. Nine individuals with GS and twelve controls, matched for age, height and weight, were assessed for plasma antioxidant status, red blood cell antioxidant enzyme activities, plasma malondialdehyde, the susceptibility of serum to copper (Cu2+) induced oxidation and blood lipid profile. Individuals with GS had significantly elevated unconjugated bilirubin (GS: 26.0±6.4; control: 9.7±3.0!mol/L; P < 0.001), increased trolox equivalent antioxidant capacity (GS: 1.59±0.07; control: 1.52±0.07 mmol/L trolox Equ; P = 0.035) and ferric reducing ability of plasma (GS: 1.09±0.16; control: 0.92±0.14 mmol/L Fe2+ Equ; P = 0.024). The lag phase of serum oxidation was significantly longer in the GS group (GS: 121.4±10.5; control: 106.8±14.6 min; P = 0.020) and was positively correlated with the bilirubin concentration (r = 0.451, P = 0.040). A trend toward elevated HDL:LDL ratio was observed in GS (GS 0.96±0.31; control: 0.73±0.21; P = 0.072). In summary, individuals with GS have an increased circulating antioxidant status and an improved resistance to serum oxidation which may partially explain their reduced prevalence of CVD