Fatty Acid- and Cholesterol Transporter Protein Expression along the Human Intestinal Tract
et al. (2010) Fatty Acid- and Cholesterol Transporter Protein Expression along the Human
Intestinal Tract. PLoS ONE 5(4): e10380. doi:10.1371/journal.pone.0010380
Fatty Acid- and Cholesterol Transporter Protein Expression along the Human Intestinal Tract
Christiaan J. Masson 0
Jogchum Plat 0
Ronald P. Mensink 0
Andrzej Namiot 0
Wojciech Kisielewski 0
Zbigniew Namiot 0
Joachim Fu llekrug 0
Robert Ehehalt 0
Jan F. C. Glatz 0
Maurice M. A. L. Pelsers 0
Hendrik W. van Veen, University of Cambridge, United Kingdom
0 1 Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre
1 , Maastricht , The Netherlands
Background: Protein distribution profiles along the human intestinal tract of transporters involved in the absorption of cholesterol and long-chain fatty acids (LCFA) have been scarcely evaluated. Methodology/Principal Findings: In post-mortem samples from 11 subjects, intestinal transporter distribution profiles were determined via Western Blot. Differences in transporter protein levels were statistically tested using ANOVA and Tukey's Post Hoc comparisons. Levels in all segments were expressed relative to those in duodenum. Except for ABCG5 and FATP4, levels (mean6SEM) were the highest in the ileum. For ABCA1, ileal levels (1.8060.26) differed significantly from those in duodenum (P = 0.049) and proximal colon (0.9260.14; P = 0.029). ABCG8 levels in ileum (1.9160.30) differed from those in duodenum (P = 0.041) and distal colon (0.8460.22; P = 0.010) and jejunum (1.6460.26) tended to be higher than distal colon (0.8460.22; P = 0.087). Ileal NPC1L1 levels (2.5660.51) differed from duodenum levels (P = 0.019) and from distal colon (1.0960.22; P = 0.030). There was also a trend (P = 0.098) for higher jejunal (2.2360.37) than duodenal NPC1L1 levels. The levels of ABCG5 did not correlate with those of ABCG8. FAT/CD36 levels in ileum (2.0360.42) differed from those in duodenum (P = 0.017), and proximal and distal colon (0.8960.13 and 0.9760.15 respectively; P = 0.011 and P = 0.014). FABPpm levels in ileum (1.0460.13) differed from proximal (0.6460.07; P = 0.026) and distal colon (0.6660.09; P = 0.037). Conclusions/Significance: The distribution profiles showed a bell-shape pattern along the GI-tract with the highest levels in ileum for ABCA1, ABCG8, NPC1L1, FATCD36 and FABPm, suggesting a prominent role for ileum in transporter-mediated uptake of cholesterol and LCFAs.
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Funding: The study was partially funded by grant 313556 L by the Medical University of Bialystok and partially by the Dutch Dairy Association (NZO). The
funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
The incidence of the metabolic syndrome (MS) has rapidly
increased over the last few decades [1,2]. MS is a clustering of
metabolic risk markers, including abdominal obesity, elevated
plasma glucose levels, and an atherogenic lipid profile, which
altogether contribute to the development of cardiovascular disease
(CVD) [3,4]. Patients suffering from the MS often show
disturbances in fatty acid (FA) metabolism [5] leading to elevated
plasma free fatty acid levels which negatively influence
insulinmediated glucose uptake [6,7]. The disturbances in lipoprotein
profiles most likely originate from an elevated hepatic production
of large triacylglycerol-rich VLDL1 particles, which in
combination with increased cholesterylester transfer protein (CETP)
mediated lipid fluxes and decreased lipoprotein lipase (LPL)
mediated lipolysis results in hypertriglyceridemia and low serum
HDL cholesterol concentration [8,9,10]. However, it becomes
more and more evident that lipoprotein metabolism is also
regulated by absorption characteristics of cholesterol and FA in the
intestine. For example, it was recently shown that the level of
cholesterol absorption from the intestine was inversely related to
reverse cholesterol transport from peripheral tissue macrophages
into the feces [11].
Concerning the MS, there is an ongoing discussion whether these
patients are characterized by elevated and/or accelerated intestinal
cholesterol absorption or not. In this respect, Miettinen et al. [12]
have proposed, that subjects can be characterized as cholesterol
absorbers (with a low cholesterol synthesis) or as cholesterol
synthesizers (with a low cholesterol absorption). Based on circulating
levels of plant sterols which can be used as markers for fractional
cholesterol absorption, it has been suggested that subjects with the
MS are rather cholesterol synthesizers than absorbers [13]. Indeed,
obese subjects displayed increased cholesterol synthesis and a
decreased fractional cholesterol absorption [14].
Intestinal cholesterol absorption is tightly regulated by a number
of transporter proteins and whether an individual is a cholesterol
absorber or cholesterol s (...truncated)