Multi-omics integrative analysis to access role of coiled-coil domain-containing 80 in lipid metabolism.

Coiled-coil domain-containing 80 (Ccdc80) is closely linked to energy homeostasis. However, the molecular mechanism remains unclear. This study aims to uncover the potential mechanism of Ccdc80 in modulating lipid metabolism by accessing the metabolic and transcriptional consequences of removing Ccdc80. We established a Ccdc80 knockout model (Ccdc80-/-) in C57BL/6 mouse. Serum and liver samples from Ccdc80+/+ (n = 8) and Ccdc80-/- (n = 8) male mice were obtained at the age of week 10. The serum metabolites and lipids were analyzed by gas chromatography-mass spectrometry and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, respectively. RNA expression microarray was performed in the livers of the same mice. Results showed that a total of 58 metabolites and 30 lipids were altered between the Ccdc80+/+ and Ccdc80-/- mice. A total of 873 hepatic differentially expressed genes (DEGs) were identified. The enrichment analysis of discriminant metabolites and lipids reflected alterations in α-linolenic acid and linoleic acid metabolism. Reactome pathway analysis of DEGs revealed a decreased hydroxylation of arachidonic acid in Ccdc80-/- mice. The Kyoto Encyclopedia of Genes and Genomes pathway result suggested a decrease of PPAR signaling and fatty acid degradation by Ccdc80-knockout. The joint pathway analysis integrating metabolomics, lipidomics and transcriptomics indicated that Ccdc80-knockout could down-regulate arachidonic acid and α-linolenic acid metabolism. These results provide new insights into the role of Ccdc80 in fatty acid metabolism.

Medium Chain Triglycerides Promote the Uptake of ß-Carotene in O/W Emulsions via Intestinal Transporter SR-B1 in Caco-2 Cells.

This study aimed to elucidate the impacts of carrier oil types (long chain triglycerides (LCT), medium chain triglycerides (MCT), and orange oil (indigestible oil)) on the micellization and cellular uptake of ß-carotene (BC) formulated in O/W emulsions, with an emphasis on the role of intestinal transporters. The micellization and cellular uptake of BC in the gastrointestinal tract were evaluated via an in vitro digestion model and a Caco-2 cell monolayer. And the interactions between lipids and intestinal transporters were monitored by nontargeted lipidomics, RT-PCR, and Western blot. The BC micellization rates followed a decreasing trend in emulsions: corn oil (69.47 ± 4.19%) > MCT (22.22 ± 0.89%) > orange oil (11.01 ± 2.86%), whereas the cellular uptake rate of BC was significantly higher in MCT emulsion (56.30 ± 20.13%) than in corn oil emulsion (14.01 ± 1.04%, p < 0.05). The knockdown of SR-B1 led to a 31.63% loss of BC cellular uptake from MCT micelles but had no effect on corn oil micelles. Lipidomics and transporter analysis revealed that TG (10:0/10:0/12:0) and TG (10:0/12:0/12:0) might be the fingerprint lipids that promoted the cellular absorption of BC-MCT micelles via stimulating the mRNA expression of SR-B1.

Deficiency of coiled-coil domain containing 80 increases plasma cholesterol by decreasing fecal sterols excretion in hypercholesterolemic mice.

Disorders in cholesterol and bile acid metabolism have been acknowledged as critical in pathogenesis of hypercholesterolemia. Coiled-coil domain containing 80 (CCDC80) has been closely linked to lipid homeostasis in mice, with its role in cholesterol metabolism yet to be fully elucidated. This study aims to uncover the regulatory mechanisms of CCDC80 in diet-induced hypercholesterolemia. We generated a CCDC80 knockout (CCDC80-/-) model in C57BL/6 mouse. The initial transcriptional and metabolic consequences of removing CCDC80 were accessed at baseline by gene expression microarrays and gas chromatography-mass spectrometry / ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, respectively. The hepatic cholesterol was investigated in both CCDC80+/+ and CCDC80-/- male mice at baseline and after feeding a high-cholesterol diet for 12 weeks. The regulatory effects of CCDC80 on gene expressions and protein masses were measured by RT-qPCR and western blot, respectively. At baseline, the KEGG pathway enrichment analysis combining metabolomics, lipidomics and transcriptomics, revealed a down-regulation of hepatic bile acid biosynthesis by CCDC80-knockout, especially for primary bile acids. In the hypercholesterolemic models, our results showed that deficiency of CCDC80 increased plasma and liver cholesterol levels, but decreased fecal neutral and acidic sterols excretion in mice. Mechanistically, we found that such effects were partly mediated by attenuating the alternative pathway of bile acid synthesis catalyzed by oxysterol 7-alpha-hydroxylase (CYP7B1). In conclusion, our results suggest CCDC80 as a novel modulator of cholesterol homeostasis in male mice. Deficiency of CCDC80 could further impair fecal sterols excretion in diet-induced hypercholesterolemia.