High-Density Lipoprotein Proteomic Composition, and not Efflux Capacity, Reflects Differential Modulation of Reverse Cholesterol Transport by Saturated and Monounsaturated Fat Diets.

Circulation

From Nutrigenomics Research Group (M.O., E.D., W.G., O.F., A. McMorrow, A. Murphy, C.L., D.J., H.M.R., F.C.M.), UCD Institute of Food and Health (M.R., M.G., E.G., L.B., H.M.R., F.C.M.), Diabetes Complications Research Centre (F.C.M.), UCD Conway Institute and School of Medicine, University College Dublin, Ireland; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA (M.d.l.L.M.); and Cardiovascular Institute (M.P.R.) and Institute for Translational Medicine and Therapeutics (M.P.R.), University of Pennsylvania School of Medicine, Philadelphia.

Published: May 2016

Background: Acute inflammation impairs reverse cholesterol transport (RCT) and reduces high-density lipoprotein (HDL) function in vivo. This study hypothesized that obesity-induced inflammation impedes RCT and alters HDL composition, and investigated if dietary replacement of saturated (SFA) for monounsaturated (MUFA) fatty acids modulates RCT.

Methods And Results: Macrophage-to-feces RCT, HDL efflux capacity, and HDL proteomic profiling was determined in C57BL/6j mice following 24 weeks on SFA- or MUFA-enriched high-fat diets (HFDs) or low-fat diet. The impact of dietary SFA consumption and insulin resistance on HDL efflux function was also assessed in humans. Both HFDs increased plasma (3)H-cholesterol counts during RCT in vivo and ATP-binding cassette, subfamily A, member 1-independent efflux to plasma ex vivo, effects that were attributable to elevated HDL cholesterol. By contrast, ATP-binding cassette, subfamily A, member 1-dependent efflux was reduced after both HFDs, an effect that was also observed with insulin resistance and high SFA consumption in humans. SFA-HFD impaired liver-to-feces RCT, increased hepatic inflammation, and reduced ABC subfamily G member 5/8 and ABC subfamily B member 11 transporter expression in comparison with low-fat diet, whereas liver-to-feces RCT was preserved after MUFA-HFD. HDL particles were enriched with acute-phase proteins (serum amyloid A, haptoglobin, and hemopexin) and depleted of paraoxonase-1 after SFA-HFD in comparison with MUFA-HFD.

Conclusions: Ex vivo efflux assays validated increased macrophage-to-plasma RCT in vivo after both HFDs but failed to capture differential modulation of hepatic cholesterol trafficking. By contrast, proteomics revealed the association of hepatic-derived inflammatory proteins on HDL after SFA-HFD in comparison with MUFA-HFD, which reflected differential hepatic cholesterol trafficking between groups. Acute-phase protein levels on HDL may serve as novel biomarkers of impaired liver-to-feces RCT in vivo.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122580PMC
http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020278DOI Listing

Publication Analysis

Top Keywords

subfamily member
16
rct vivo
12
liver-to-feces rct
12
hdl
9
high-density lipoprotein
8
efflux capacity
8
differential modulation
8
reverse cholesterol
8
cholesterol transport
8
rct
8

Similar Publications

Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfamily DUBs, it performs cysteine proteolytic isopeptide bond cleavage; however, its exact catalytic mechanism is not yet resolved. In this work, we used different computational approaches to get molecular insights into the Cezanne-2 catalytic mechanism.

View Article and Find Full Text PDF

Chemotherapy resistance is a great challenge in the treatment of gastric cancer (GC), so it is urgent to explore the prognostic markers of chemoresistance. PUF60 (Poly (U)-binding splicing factor 60) is a nucleic acid-binding protein that has been shown to regulate transcription and link to tumorigenesis in various cancers. However, its biological role and function in chemotherapy resistance of GC is unclear.

View Article and Find Full Text PDF

New naphthalene-linked pyrazoline-thiazole hybrids as prominent antilung and antibreast cancer inhibitors.

Turk J Chem

November 2024

Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), pioneer members of the receptor tyrosine kinase subfamily, are frequently mutated and/or overexpressed in several types of human cancers, including nonsmall cell lung cancer (NSCLC) and breast cancer, which are leading causes of cancer-related deaths worldwide. EGFR and HER2-focused anti-NSCLC and antibreast cancer studies encouraged us to search for new potential agents. For this purpose, in the current work, naphthalene-linked pyrazoline-thiazole hybrids (- and -) were synthesized and examined for their antiproliferative effects on A549 NSCLC and MCF-7 breast cancer cell lines.

View Article and Find Full Text PDF

Dinucleases of the DEDD superfamily, such as oligoribonuclease, Rexo2 and nanoRNase C, catalyze the essential final step of RNA degradation, the conversion of di- to mononucleotides. The active sites of these enzymes are optimized for substrates that are two nucleotides long, and do not discriminate between RNA and DNA. Here, we identified a novel DEDD subfamily, members of which function as dedicated deoxydinucleases (diDNases) that specifically hydrolyze single-stranded DNA dinucleotides in a sequence-independent manner.

View Article and Find Full Text PDF

The ATP-binding cassette transporter subfamily C member 8 (ABCC8) regulates insulin secretion from β-cells. Loss- and gain-of-function variants of have been implicated in neonatal hyperinsulinemic hypoglycemia and young-onset diabetes, respectively. Although some patients with variants have been reported to exhibit both neonatal hypoglycemia and young-onset diabetes, the molecular and clinical characteristics of this atypical phenotype remain unknown.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!