Journal: Journal of the Endocrine Society

Article Title: Acyl-CoA Synthetase 5 Knockout and Inhibitors Protect Against Diet-Induced Obesity in Mice by Activating the Ileal Brake

doi: 10.1210/jendso/bvaf196

Figure Lengend Snippet: Effect of ACSL5 deficiency on gastric emptying and active GLP-1 levels. (A) Chow-fed male Acsl5 KO (n = 3) and WT (n = 3) mice received IV tyloxapol followed by an oral gavage of olive oil containing 3 H triolein. After 6 hours, blood, feces, and the indicated organs were collected and 3 H activity was measured in each sample. KO different from WT, ** P < .01. (B) Chow-fed male WT mice received IV tyloxapol followed by an oral gavage of olive oil containing 3 H triolein and either vehicle (n = 10), 3 mg/kg LP-911884 (884; n = 10) or 3 mg/kg LP-911888 (888; n = 10). After 6 hours, blood and stomach were collected and 3 H activity was measured in each sample. LP-911888 different from vehicle and from LP-911884 groups, *** P < .001. (C) Chow-fed male Acsl5 KO (n = 8) and WT (n = 4) mice received IV tyloxapol followed by an oral gavage of olive oil containing 3 H triolein and either vehicle (n = 4 KO mice, n = 4 WT mice) or 100 mg/kg orlistat (n = 4 KO mice). After 6 hours, blood, stomach, small intestine (Sm Int), and feces were collected and 3 H activity was measured in each sample. (D) Chow-fed male WT mice received IV tyloxapol followed by an oral gavage of olive oil containing 3 H triolein and either vehicle (n = 7), vehicle + 100 mg orlistat (n = 10), 30 mg/kg LP-856866 (n = 18), or both compounds (n = 10). After 6 hours, blood and stomach were collected and 3 H activity was measured in each sample. † Statistical analysis by Kruskal-Wallis test followed by Dunn's multiple comparisons test. For panels A-D, data reported as % of gavaged DPM. Chow-fed male (E) and female (F) Acsl5 KO and WT mice (n = 5-10/group) were fasted overnight, pretreated with either vehicle (10% solutol) or sitagliptin (30 mg/kg) by oral gavage, and then provided a liquefied 45% HFD meal by oral gavage 30 minutes later. Plasma samples for aGLP-1 levels were obtained at 5, 30, and 120 minutes after administration of the 45% HFD meal. (G) Chow-fed male WT mice (n = 5/group) were fasted overnight, pretreated with either vehicle (10% solutol), 30 mg/kg sitagliptin, 60 mg/kg LP-856866, or both compounds by oral gavage, and then provided a liquefied 45% HFD meal by oral gavage 30 minutes later. Plasma samples for aGLP-1 levels were obtained at baseline and then at 5, 10, 15, 30, 60, 120, and 240 minutes after administration of the 45% HFD meal. Data in panels E-G were analyzed by 2-way ANOVA. Interaction between LP-856866 and sitagliptin: a , P < .05; b , P < .01; c , P < .001. Sitagliptin different from vehicle: d , P < .01; e , P < .001. KO different from vehicle: f , P < .05; g , P < .001.

Article Snippet: After an overnight fast, male and female mice received 100 μL of tyloxapol (Triton WR1339, catalog #T-8761; Sigma-Aldrich, St. Louis, MO) as a 20% solution in 0.9% NaCl, by tail vein injection, followed by a 10 μL/g oral gavage bolus of olive oil containing 3 H triolein (glycerol tri [9,10 (n)- 3 H] oleate, American Radiolabeled Chemicals, St. Louis, MO), where 3 H triolein (1 μCi/μL) was mixed with olive oil at a ratio of 1 μL (1 mCi) 3 H triolein to 299 μL olive oil.

Techniques: Activity Assay, Clinical Proteomics