Enhanced stem cell engraftment and modulation of hepatic reactive oxygen species production in diet-induced obesity.

Nyamandi VZ, Johnsen VL, Hughey CC, Hittel DS, Khan A, Newell C, Shearer J
Obesity (Silver Spring). 2014 22 (3): 721-9

PMID: 23894091 · DOI:10.1002/oby.20580

OBJECTIVE - The impact of dietary-induced obesity (DIO) on stem cell engraftment and the respective therapeutic potential of stem cell engraftment in DIO have not been reported. The objectives of this study were to examine the impact of DIO on the survival and efficacy of intravenous bone marrow-derived mesenchymal stem cell (MSC) administration in the conscious C57BL/6 mouse.

METHODS - Male mice consumed either a chow (CH) or high fat (HF, 60% kcal) diet for 18 weeks and were subsequently treated with MSC over a 6-day period. Key measurements included tissue-specific cell engraftment, glucose and insulin sensitivity, inflammation, and oxidative stress.

RESULTS - MSC administration had no effect on inflammatory markers, glucose, or insulin sensitivity. DIO mice showed increases in MSC engraftment in multiple tissues compared with their CH counterparts. Engraftment was increased in the HF liver where MSC administration attenuated DIO-induced oxidative stress. These liver-specific alterations in HF-MSC were associated with increases in stanniocalcin-1 (STC1) and uncoupling protein 2 (UCP2), which contribute to cell survival and modulate mitochondrial bioenergetics.

CONCLUSION - Results suggest that MSC administration in DIO promotes engraftment and mitigates hepatic oxidative stress. These data invite further exploration into the therapeutic potential of stem cells for the treatment of DIO oxidative stress in the liver.

© 2013 The Obesity Society.

MeSH Terms (18)

Administration, Intravenous Animals Blood Glucose Diet, High-Fat Glycoproteins Inflammation Insulin Resistance Ion Channels Liver Male Mesenchymal Stem Cells Mice Mice, Inbred C57BL Mitochondrial Proteins Obesity Oxidative Stress Reactive Oxygen Species Uncoupling Protein 2

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