title: Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice.
abstract: Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout (KO) does not affect Western diet-induced obesity nor adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 KO mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp. These results suggest that Sort1 loss-of-function in vivo does not affect obesity development, but differentially modulates adipose glucose metabolism under fasting and insulin-stimulated states.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, KS, USA.
authors.forename: Jibiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, KS, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Matye
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, KS, USA.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, KS, USA.
authors.forename: Tiangang
authors.initials: T
authors.lastname: Li
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency* / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001481:Basal Metabolism; D002518:Ceramides / Q000378:metabolism; D066273:Diet, Western / Q000009:adverse effects; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006019:Glycolysis; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002518:Ceramides; D005227:Fatty Acids; D005947:Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000099183:Sortilin
keywords: cholesterol; diabetes; hyperlipidemia; obesity