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AGE

, Volume 34, Issue 5, pp 1225–1237 | Cite as

Decreased insulin sensitivity and increased oxidative damage in wasting adipose tissue depots of wild-type mice

  • Lucila Sackmann-Sala
  • Darlene E. Berryman
  • Ellen R. Lubbers
  • Clare B. Vesel
  • Katie M. Troike
  • Edward O. List
  • Rachel D. Munn
  • Yuji Ikeno
  • John J. Kopchick
Article

Abstract

Unintentional weight loss (wasting) in the elderly is a major health concern as it leads to increased mortality. Several studies have focused on muscle loss, but little is known about the mechanisms giving rise to loss of fat mass at old ages. To investigate potential mechanisms, white adipose tissue (WAT) characteristics and proteomic profiles were compared between adult (10–12-month-old) and aged (22–24-month-old) wild-type mice. Four individual WAT depots were analyzed to account for possible depot-specific differences. Proteomic profiles of WAT depots, along with body weights and compositions, plasma levels of insulin, leptin and adiponectin, insulin tolerance, adipocyte sizes, and products of oxidative damage in each WAT depot were determined. We found that lean mass remained constant while fat mass and insulin tolerance were decreased in old age, as were adipocyte sizes in the WAT depots. Proteomic results showed increased levels of enolase, pyruvate dehydrogenase E1β, NAD+−dependent isocitrate dehydrogenase α, and ATP synthase subunit β, and decreased levels of carbonic anhydrase 3 in WAT of aged mice. These data suggest increased aerobic glucose oxidation in wasting WAT, consistent with decreased insulin signaling. Also, Cu/Zn superoxide dismutase and two chaperones were increased in aged WAT depots, indicating higher stress resistance. In agreement, lipid peroxidation (HNE-His adducts) increased in old age, although protein oxidation (carbonyl groups) showed no increase. In conclusion, features of wasting WAT were similar in the four depots, including decreased adipocyte sizes and alterations in protein expression profiles that indicated decreased insulin sensitivity and increased lipid peroxidation.

Keywords

Wasting Aging White adipose tissue depots Proteomics Oxidative damage Stress resistance Insulin resistance 

Abbreviations

2DE

2-Dimensional gel electrophoresis

CA-III

Carbonic anhydrase 3

E-FABP

Epidermal fatty acid binding protein

HMW

High molecular weight

HNE

4-Hydroxynonenal

Idh3α

Isocitrate dehydrogenase [NAD+] α

ITT

Insulin tolerance test

LPL

Lipoprotein lipase

MALDI-TOF

Matrix assisted laser desorption/ionization time-of-flight

MS

Mass spectrometry

MS/MS

Tandem MS

PDHE1-B

Pyruvate dehydrogenase E1 subunit β

ROS

Reactive oxygen species

WAT

White adipose tissue

Notes

Acknowledgements

This work was supported in part by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by the National Institutes of Health (NIH) grants DK075436-01, AG019899-06, and 1P01AG031736-01A1, by the Diabetes Research Initiative and the BioMolecular Innovation and Technology Partnership at Ohio University, and by American Veterans (AMVETS). This work is MIAPE compliant.

Supplementary material

11357_2011_9304_MOESM1_ESM.pdf (647 kb)
Esm 1 Decreased insulin sensitivity and increased oxidative damage in wasting adipose tissue depots of wild-type mice (PDF 646 kb)

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Copyright information

© American Aging Association 2011

Authors and Affiliations

  • Lucila Sackmann-Sala
    • 1
    • 2
    • 3
  • Darlene E. Berryman
    • 1
    • 3
    • 4
  • Ellen R. Lubbers
    • 1
  • Clare B. Vesel
    • 1
  • Katie M. Troike
    • 1
  • Edward O. List
    • 1
  • Rachel D. Munn
    • 1
  • Yuji Ikeno
    • 6
  • John J. Kopchick
    • 1
    • 3
    • 5
  1. 1.Edison Biotechnology InstituteOhio UniversityAthensUSA
  2. 2.Department of Biological Sciences, College of Arts and SciencesOhio UniversityAthensUSA
  3. 3.Molecular and Cellular Biology ProgramOhio UniversityAthensUSA
  4. 4.School of Applied Health Sciences and Wellness, College of Health Sciences and ProfessionsOhio UniversityAthensUSA
  5. 5.Department of Biomedical Sciences, College of Osteopathic MedicineOhio UniversityAthensUSA
  6. 6.Barshop Institute for Longevity and Aging StudiesUniversity of Texas Health Science Center at San AntonioSan AntonioUSA

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