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Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.

Publication ,  Journal Article
Kim, D-H; Sartor, MA; Bain, JR; Sandoval, D; Stevens, RD; Medvedovic, M; Newgard, CB; Woods, SC; Seeley, RJ
Published in: Diabetes
September 2012

A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. Glucose tolerance tests were performed on days 2 and 3 of treatment with vehicle (HF-V) or proapoptotic peptide (HF-PP) and mice pair-fed to HF-PP (HF-PF) in obese mice on a high-fat diet (HFD). Serum metabolic variables, including lipid profile, adipokines, individual fatty acids, and acylcarnitines, were measured. Microarray analysis was performed in epididymal fat of lean or obese mice treated with vehicle or proapoptotic peptide (PP). PP rapidly and potently improved glucose tolerance of obese mice in a weight- and food intake-independent manner. Serum insulin and triglycerides were decreased in HF-PP relative to HF-V. Levels of fatty acids and acylcarnitines were distinctive in HF-PP compared with HF-V or HF-PF. Microarray analysis in AT revealed that pathways involved in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation were changed by exposure to HFD and were reversed by PP administration. These studies suggest a novel role of the AT vasculature in glucose homeostasis and lipid metabolism.

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Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

September 2012

Volume

61

Issue

9

Start / End Page

2299 / 2310

Location

United States

Related Subject Headings

  • Triglycerides
  • Peptides
  • Mitochondria
  • Mice, Inbred C57BL
  • Mice
  • Metabolic Networks and Pathways
  • Male
  • Lipid Metabolism
  • Intercellular Signaling Peptides and Proteins
  • Homeostasis
 

Citation

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Kim, D.-H., Sartor, M. A., Bain, J. R., Sandoval, D., Stevens, R. D., Medvedovic, M., … Seeley, R. J. (2012). Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes, 61(9), 2299–2310. https://doi.org/10.2337/db11-1579
Kim, Dong-Hoon, Maureen A. Sartor, James R. Bain, Darleen Sandoval, Robert D. Stevens, Mario Medvedovic, Christopher B. Newgard, Stephen C. Woods, and Randy J. Seeley. “Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.Diabetes 61, no. 9 (September 2012): 2299–2310. https://doi.org/10.2337/db11-1579.
Kim D-H, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, et al. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012 Sep;61(9):2299–310.
Kim, Dong-Hoon, et al. “Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.Diabetes, vol. 61, no. 9, Sept. 2012, pp. 2299–310. Pubmed, doi:10.2337/db11-1579.
Kim D-H, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, Newgard CB, Woods SC, Seeley RJ. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012 Sep;61(9):2299–2310.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

September 2012

Volume

61

Issue

9

Start / End Page

2299 / 2310

Location

United States

Related Subject Headings

  • Triglycerides
  • Peptides
  • Mitochondria
  • Mice, Inbred C57BL
  • Mice
  • Metabolic Networks and Pathways
  • Male
  • Lipid Metabolism
  • Intercellular Signaling Peptides and Proteins
  • Homeostasis