Identification of the Major Intestinal Fatty Acid Transport Protein

Stahl, Andreas; Hirsch, David J.; Gimeno, Ruth E.; Punreddy, Sandhya; Ge, Pei; Watson, Nicki; Patel, Shraddha; Kotler, Mariana; Raimondi, Alejandra; Tartaglia, Louis A.; Lodish, Harvey F.

doi:10.1016/s1097-2765(00)80332-9

Cited by 362 publications

(337 citation statements)

References 40 publications

(9 reference statements)

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“…Primary hepatocytes were prepared by two-step perfusion with liver perfusion and digestion medium, according to the manufacturer's instructions (Invitrogen), and were immediately used for uptake assays. Fluorescence-activated cell sorter-based short-term (30 sec) FA uptake assays were performed as described (24).…”

Section: Glucose Tolerance Test (Gtt)mentioning

confidence: 99%

Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity

Stiles

Wang²,

Stahl³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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396

416

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In the liver, insulin controls both lipid and glucose metabolism through its cell surface receptor and intracellular mediators such as phosphatidylinositol 3-kinase and serine-threonine kinase AKT. The insulin signaling pathway is further modulated by protein tyrosine phosphatase or lipid phosphatase. Here, we investigated the function of phosphatase and tension homologue deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, by targeted deletion of Pten in murine liver. Deletion of Pten in the liver resulted in increased fatty acid synthesis, accompanied by hepatomegaly and fatty liver phenotype. Interestingly, Pten liver-specific deletion causes enhanced liver insulin action with improved systemic glucose tolerance. Thus, deletion of Pten in the liver may provide a valuable model that permits the study of the metabolic actions of insulin signaling in the liver, and PTEN may be a promising target for therapeutic intervention for type 2 diabetes

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Section: Glucose Tolerance Test (Gtt)mentioning

confidence: 99%

Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity

Stiles

Wang²,

Stahl³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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396

416

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“…Although fatty acids are hydrophobic and are capable of rapidly diffusing through the lipid bilayer when present in high concentrations [41], a large body of evidence supports the presence of a protein-mediated carrier system that operates at low substrate concentrations [24,42]. I-FABP and FATP4 are thought to be key factors for long-chain fatty acid uptake in enterocytes [24,25], whereas NPC1L1 is thought to play a critical role in intestinal cholesterol absorption [26,27]. Our present results demonstrate that isoleucine and whey downregulated the expression of i-FABP, FATP4, and NPC1L1, with a plateau at 2.0% concentration corresponding to about 65% inhibition of i-FABP, 60% of FABP, and 70% of NPC1L1.…”

Section: Discussionmentioning

confidence: 99%

“…Three key transcription factors, designated sterol regulatory element binding proteins (SREBPs) 1a, 1c, and 2, regulate the transcription of genes involved in fatty acid and cholesterol synthesis including acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) [23]. In addition, intestinal-type fatty acid binding protein (i-FABP) and fatty acid transport protein-4 (FATP4) are thought to be important factors for long-chain fatty acid uptake in enterocytes [24,25], whereas Niemann-Pick C-1-like-1 protein (NPC1L1) is thought to be the principal intestinal cholesterol transporter [26,27].…”

Section: Introductionmentioning

confidence: 99%

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Chen¹,

Reimer²

2009

Nutrition

143

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Objective-A growing body of evidence supports an antiobesity effect of dairy products; however, the mechanisms remain unclear. The objective of this study was to explore possible intestinal mechanisms by which dairy delivers an antiobesity effect. The human intestinal cell line, NCI-H716, was used to test the hypothesis that branched-chain amino acids and dairy proteins regulate satiety hormone secretion and modulate genes involved in fatty acid and cholesterol metabolism.Methods-In dose-response (0.5%, 1.0%, 2.0%, and 3.0%) studies, the effect of leucine, isoleucine, valine, skim milk, casein, and whey on glucagon-like peptide-1 release and the expression of selected genes were tested.Results-Leucine, isoleucine, skim milk, and casein stimulated glucagon-like peptide-1 release (P < 0.05). Isoleucine and whey downregulated the expression of intestinal-type fatty acid binding protein (i-FABP), fatty acid transport protein 4 (FATP4), Niemann-Pick C-1-like-1 protein (NPC1L1), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein-2 (SREBP-2), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR; P < 0.05). Leucine and valine downregulated the expression of NPC1L1, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Casein downregulated the expression of i-FABP, FATP4, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Skim milk downregulated the expression of ACC, FAS, and SREBP-2, but not i-FABP, FATP4, and NPC1L1.Conclusion-This work suggests that the antiobesity effect of dairy may be mediated, at least in part, by integration of events that promote glucagon-like peptide-1 secretion and inhibit expression of genes involved in intestinal fatty acid and cholesterol absorption and synthesis.

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“…However, the expression was significantly reduced in the jejunum (fc: 21.87, DON5). In primary enterocytes treated with SLC27A4 antisense, palmitate and oleate uptake were reduced simultaneously (Stahl et al, 1999). Maresca et al (2002) reported an increased palmitate uptake by 35% in their study after challenging HT-29-D4 cells with DON.…”

Section: Nutrient Transportmentioning

confidence: 91%

Fusarium mycotoxin-contaminated wheat containing deoxynivalenol alters the gene expression in the liver and the jejunum of broilers

Dietrich

Neuenschwander

Bucher

et al. 2012

Animal

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The effects of mycotoxins in the production of animal feed were investigated using broiler chickens. For the feeding trial, naturally Fusarium mycotoxin-contaminated wheat was used, which mainly contained deoxynivalenol (DON). The main effects of DON are reduction of the feed intake and reduced weight gain of broilers. At the molecular level, DON binds to the 60 S ribosomal subunit and subsequently inhibits protein synthesis at the translational level. However, little is known about other effects of DON, for example, at the transcriptional level. Therefore, a microarray analysis was performed, which allows the investigation of thousands of transcripts in one experiment. In the experiment, 20 broilers were separated into four groups of five broilers each at day 1 after hatching. The diets consisted of a control diet and three diets with calculated, moderate concentrations of 1.0, 2.5 and 5.0 mg DON/kg feed, which was attained by exchanging uncontaminated wheat with naturally mycotoxin-contaminated wheat up to the intended DON concentration. The broilers were held at standard conditions for 23 days. Three microarrays were used per group to determine the significant alterations of the gene expression in the liver (P , 0.05), and qPCR was performed on the liver and the jejunum to verify the results. No significant difference in BW, feed intake or feed conversion rate was observed. The nutrient uptake into the hepatic and jejunal cells seemed to be influenced by genes: SLC2A5 (fc: 21.54, DON2.5), which facilitates glucose and fructose transport and SLC7A10 (fc: 11.49, DON5), a transporter of D-serine and other neutral amino acids. In the jejunum, the palmitate transport might be altered by SLC27A4 (fc: 21.87, DON5) and monocarboxylates uptake by SLC16A1 (fc: 21.47, DON5). The alterations of the SLC gene expression may explain the reduced weight gain of broilers chronically exposed to DON-contaminated wheat. The decreased expressions of EIF2AK3 (fc: 21.29, DON2.5/5) and DNAJC3 (fc: 21.44, DON2.5) seem to be related to the translation inhibition. The binding of DON to the 60 S ribosomal subunit and the subsequent translation inhibition might be counterbalanced by the downregulation of EIF2AK3 and DNAJC3. The genes PARP1, MPG, EME1, XPAC, RIF1 and CHAF1B are mainly related to single-strand DNA modifications and showed an increased expression in the group with 5 mg DON/kg feed. The results indicate that significantly altered gene expression was already occurring at 2.5 mg DON/kg feed.

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Identification of the Major Intestinal Fatty Acid Transport Protein

Cited by 362 publications

References 40 publications

Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity

Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Fusarium mycotoxin-contaminated wheat containing deoxynivalenol alters the gene expression in the liver and the jejunum of broilers

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