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

Dong-Hun Kim, Maureen A. Sartor, James R. Bain, Darleen Sandoval, Robert D. Stevens, Mario Medvedovic, Christopher B. Newgard, Stephen C. Woods, Randy J. Seeley

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2299-2310
Number of pages12
JournalDiabetes
Volume61
Issue number9
DOIs
Publication statusPublished - 2012 Sep 1

Fingerprint

Endothelium
Adipose Tissue
Apoptosis
Weights and Measures
Glucose
Peptides
Obese Mice
White Adipose Tissue
High Fat Diet
Microarray Analysis
Fatty Acids
Branched Chain Amino Acids
Adipokines
Oxidative Phosphorylation
Adiposity
Glucose Tolerance Test
Serum
Lipid Metabolism
Triglycerides
Homeostasis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. / Kim, Dong-Hun; Sartor, Maureen A.; Bain, James R.; Sandoval, Darleen; Stevens, Robert D.; Medvedovic, Mario; Newgard, Christopher B.; Woods, Stephen C.; Seeley, Randy J.

In: Diabetes, Vol. 61, No. 9, 01.09.2012, p. 2299-2310.

Research output: Contribution to journalArticle

Kim, D-H, Sartor, MA, Bain, JR, Sandoval, D, Stevens, RD, Medvedovic, M, Newgard, CB, Woods, SC & Seeley, RJ 2012, '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, pp. 2299-2310. https://doi.org/10.2337/db11-1579
Kim, Dong-Hun ; Sartor, Maureen A. ; Bain, James R. ; Sandoval, Darleen ; Stevens, Robert D. ; Medvedovic, Mario ; Newgard, Christopher B. ; Woods, Stephen C. ; Seeley, Randy J. / Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. In: Diabetes. 2012 ; Vol. 61, No. 9. pp. 2299-2310.
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