Possible Role of Intestinal Fatty Acid Oxidation in the Eating-Inhibitory Effect of the PPAR-α Agonist Wy-14643 in High-Fat Diet Fed Rats
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{"title"=>"Possible Role of Intestinal Fatty Acid Oxidation in the Eating-Inhibitory Effect of the PPAR-α Agonist Wy-14643 in High-Fat Diet Fed Rats", "type"=>"journal", "authors"=>[{"first_name"=>"Elnaz", "last_name"=>"Karimian Azari", "scopus_author_id"=>"55856772700"}, {"first_name"=>"Claudia", "last_name"=>"Leitner", "scopus_author_id"=>"23970655200"}, {"first_name"=>"Thomas", "last_name"=>"Jaggi", "scopus_author_id"=>"55857889100"}, {"first_name"=>"Wolfgang", "last_name"=>"Langhans", "scopus_author_id"=>"7007166439"}, {"first_name"=>"Abdelhak", "last_name"=>"Mansouri", "scopus_author_id"=>"23480427100"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369833883", "sgr"=>"84884227355", "issn"=>"19326203", "pmid"=>"24069361", "scopus"=>"2-s2.0-84884227355", "doi"=>"10.1371/journal.pone.0074869"}, "id"=>"5788646a-a33a-349f-a518-2f9409b67fe7", "abstract"=>"PPAR-α plays a key role in lipid metabolism; it enhances fatty acid oxidation (FAO) and ketogenesis. Pharmacological PPAR-α activation improves insulin sensitivity and reduces food intake, but its mechanisms of action remain unknown. We here report that intraperitoneal (IP) administration of the PPAR-α agonist Wy-14643 (40 mg/kg BW) reduced food intake in adult male rats fed a high-fat diet (HFD, 49% of the energy) mainly through an increase in the latency to eat after injection, and without inducing a conditioned taste avoidance. Also, IP administered Wy-14643 caused an acute (the first 60 min) decrease in the respiratory quotient (RQ) and an increase in hepatic portal vein β-hydroxybutyrate level (at 35 min) without affecting plasma non-esterified fatty acids. Given the known stimulatory effect of PPAR-α on FAO and ketogenesis, we measured the protein expression level of carnitine palmitoyltransferase-1 (CPT 1A) and mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMG-CoAS2), two key enzymes for FAO and ketogenesis, respectively, in liver, duodenum and jejunum. Wy-14643 induced a significant increase in the expression of CPT 1A in the jejunum and duodenum and of HMG-CoAS2 in the jejunum, but neither CPT 1A nor HMG-CoAS2 expression was increased in the liver. The induction of CPT 1A and HMG-CoAS2 expression was associated with a decrease in the lipid droplet content selectively in the jejunum. Our findings indicate that Wy-14643 stimulates FAO and ketogenesis in the intestine, in particular in the jejunum, rather than in the liver, thus supporting the hypothesis that PPAR-α activation inhibits eating by stimulating intestinal FAO.", "link"=>"http://www.mendeley.com/research/possible-role-intestinal-fatty-acid-oxidation-eatinginhibitory-effect-ppar%CE%B1-agonist-wy14643-highfat", "reader_count"=>6, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Ph. D. Student"=>3, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Ph. D. Student"=>3, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1206917"], "description"=>"<p>Carnitine palmitoyltransferase 1A (CPT 1A) (top), mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoAS2) (bottom) and β-actin in the liver (A), the duodenum (B) and the jejunum (C) were analyzed by Western blotting 1h after IP administration of Wy-14643 (40 mg/kg/ml). Panels below the graphs show representative blots; upper panels show quantification of protein levels after normalization to β-actin. Data are presented relative to the vehicle (100%) and each bar represent median with 25th/75th percentiles (* <i>P</i><0.05; Mann-Whitney U test).</p>", "links"=>[], "tags"=>["intraperitoneal", "wy-14643"], "article_id"=>801338, "categories"=>["Biological Sciences"], "users"=>["Elnaz Karimian Azari", "Claudia Leitner", "Thomas Jaggi", "Wolfgang Langhans", "Abdelhak Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074869.g005", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_intraperitoneal_IP_administration_of_Wy_14643_on_the_protein_expression_pattern_/801338", "title"=>"Effect of intraperitoneal (IP) administration of Wy-14643 on the protein expression pattern.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:44:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206912"], "description"=>"<p>IP administered Wy-14643 (40 mg/kg/ml) on meal patterns in ad libitum HFD-fed rats (n = 23). Wy-14643 increased the latency of the first meal (<b>A</b>) and decreased the second meal size (<b>E</b>), but did not significantly affect first meal size and duration (<b>B</b>, <b>C</b>), intermeal interval (<b>D</b>) and second meal duration (<b>F</b>). Data for first meal size are presented as median with percentiles and were analyzed with Wilcoxon Signed Ranks Test. Results for the other parameters (latency to eat, first meal duration, second meal size and duration) are presented as means ± SEM and were analyzed using a paired <i>t</i>-test. ** Significant difference (<i>P</i> < 0.01) compared to vehicle.</p>", "links"=>[], "tags"=>["intraperitoneally", "injected", "wy-14643"], "article_id"=>801333, "categories"=>["Biological Sciences"], "users"=>["Elnaz Karimian Azari", "Claudia Leitner", "Thomas Jaggi", "Wolfgang Langhans", "Abdelhak Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074869.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_intraperitoneally_IP_injected_Wy_14643_on_meal_pattern_/801333", "title"=>"Effect of intraperitoneally (IP) injected Wy-14643 on meal pattern.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:44:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206919"], "description"=>"<p>The picture shows a representative photographic representation of lipid droplets (green) within the cytosol (pink) of the intestinal mucosa of the jejunum (<b>A</b>) of a rat treated with IP Wy-14643 (40 mg/kg/ml, right) or vehicle (1 ml/kg, DMSO: saline 70:30, left) (Color: blue = nuclei). Each bar represent median with 25th/75th percentiles of 19 rat of the number of lipid droplets (<b>B</b>) within the cytosol [cytosol expressed as area per pixel (px<sup>2</sup>)] and the area occupied by lipid droplets (<b>C</b>) of the liver and intestinal mucosa in percent. * Significantly different from vehicle (<i>P</i>< 0.05).</p>", "links"=>[], "tags"=>["intraperitoneal", "wy-14643", "lipid"], "article_id"=>801340, "categories"=>["Biological Sciences"], "users"=>["Elnaz Karimian Azari", "Claudia Leitner", "Thomas Jaggi", "Wolfgang Langhans", "Abdelhak Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074869.g006", "stats"=>{"downloads"=>3, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_intraperitoneal_IP_administration_of_Wy_14643_on_lipid_droplets_/801340", "title"=>"Effects of intraperitoneal (IP) administration of Wy-14643 on lipid droplets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:44:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206916"], "description"=>"<p>Respiratory quotient (<b>A</b>), spontaneous locomotor activity (<b>B</b>), energy expenditure and body temperature (<b>C</b>, <b>D</b>) were assessed during 12 h following IP administration of Wy-14643 (40 mg/kg/ml). * and** significantly different from vehicle (*<i>P</i> < 0.05, **<i>P</i> < 0.01; Wilcoxon Signed Ranks Test, data presented as median with 25th/75th percentiles.</p>", "links"=>[], "tags"=>["intraperitoneal", "wy-14643"], "article_id"=>801337, "categories"=>["Biological Sciences"], "users"=>["Elnaz Karimian Azari", "Claudia Leitner", "Thomas Jaggi", "Wolfgang Langhans", "Abdelhak Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074869.g004", "stats"=>{"downloads"=>2, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_intraperitoneal_IP_administration_of_Wy_14643_on_energy_homeostasis_/801337", "title"=>"Effect of intraperitoneal (IP) administration of Wy-14643 on energy homeostasis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:44:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206913"], "description"=>"<p>β-hydroxybutyrate (BHB) (<b>A</b>) and non-esterified fatty acids (NEFA) (<b>B</b>) levels were assessed 45 min before (baseline), 35 and 70 min after treatment (Wy-14643, 40 mg/kg/ml) and 3g HFD test meal. ** Significant difference compared to vehicle (<i>P</i> < 0.01; Wilcoxon Signed Ranks Test, data are presented as median with 25th/75th percentiles.</p>", "links"=>[], "tags"=>["intraperitoneal", "wy-14643", "plasma"], "article_id"=>801334, "categories"=>["Biological Sciences"], "users"=>["Elnaz Karimian Azari", "Claudia Leitner", "Thomas Jaggi", "Wolfgang Langhans", "Abdelhak Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074869.g003", "stats"=>{"downloads"=>2, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_intraperitoneal_IP_administration_of_Wy_14643_on_plasma_metabolites_/801334", "title"=>"Effects of intraperitoneal (IP) administration of Wy-14643 on plasma metabolites.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:44:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206909"], "description"=>"<p>(<b>A</b>) IP injected Wy-14643 (10, 20, 40 or 80 mg/kg/ml) dose-dependently reduced cumulative food intake (FI) in ad libitum HFD-fed rats (n=23). * Less than vehicle (<i>P</i> < 0.05), ** less than vehicle (<i>P</i> < 0.01), Mann-Whitney U test. (<b>B</b>) IP administered Wy-14643 (40 mg/kg/ml, n=10) did not reduce saccharin solution intake (% of total fluid intake) vs. water in a two-bottle preference test, whereas LiCl (60 mg/kg in 9.4 ml/kg H<sub>2</sub>O, n = 3) did. The height of each bar represents the median and the top and bottom of each bar shows 75th and 25th percentile respectively. * Significantly different from vehicle (<i>P</i> = 0.05).</p>", "links"=>[], "tags"=>["intraperitoneally", "injected", "wy-14643"], "article_id"=>801330, "categories"=>["Biological Sciences"], "users"=>["Elnaz Karimian Azari", "Claudia Leitner", "Thomas Jaggi", "Wolfgang Langhans", "Abdelhak Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074869.g001", "stats"=>{"downloads"=>2, "page_views"=>55, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_intraperitoneally_IP_injected_Wy_14643_on_food_intake_/801330", "title"=>"Effect of intraperitoneally (IP) injected Wy-14643 on food intake.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-17 01:44:06"}

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Relative Metric

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