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

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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.

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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

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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.

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Authors and Affiliations

  1. Edison Biotechnology Institute, Ohio University, 1 Water Tower Dr., The Ridges, Athens, OH, 45701, USA

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

  2. Department of Biological Sciences, College of Arts and Sciences, Ohio University, 1 Water Tower Dr., The Ridges, Athens, OH, 45701, USA

    Lucila Sackmann-Sala

  3. Molecular and Cellular Biology Program, Ohio University, 1 Water Tower Dr., The Ridges, Athens, OH, 45701, USA

    Lucila Sackmann-Sala, Darlene E. Berryman & John J. Kopchick

  4. School of Applied Health Sciences and Wellness, College of Health Sciences and Professions, Ohio University, 1 Water Tower Dr., The Ridges, Athens, OH, 45701, USA

    Darlene E. Berryman

  5. Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, 1 Water Tower Dr., The Ridges, Athens, OH, 45701, USA

    John J. Kopchick

  6. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX, 78245, USA

    Yuji Ikeno

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  1. Lucila Sackmann-Sala
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  2. Darlene E. Berryman
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  3. Ellen R. Lubbers
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  7. Rachel D. Munn
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  8. Yuji Ikeno
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  9. John J. Kopchick
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Correspondence to John J. Kopchick.

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Sackmann-Sala, L., Berryman, D.E., Lubbers, E.R. et al. Decreased insulin sensitivity and increased oxidative damage in wasting adipose tissue depots of wild-type mice. AGE 34, 1225–1237 (2012). https://doi.org/10.1007/s11357-011-9304-7

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