High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity

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  • Pal, Anandita
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
  • Lin, Chien-Te
    • Other Affiliation: East Carolina University
  • Boykov, Ilya
    • Other Affiliation: East Carolina University
  • Benson, Emily
    • Other Affiliation: Cleveland Clinic
  • Kidd, Grahame
    • Other Affiliation: Cleveland Clinic
  • Fisher-Wellman, Kelsey H.
    • Other Affiliation: East Carolina University
  • Neufer, P. Darrell
    • Other Affiliation: East Carolina University
  • Shaikh, Saame Raza
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Diet-induced obesity impairs mitochondrial respiratory responses in tissues that are highly metabolically active, such as the heart. However, less is known about the impact of obesity on the respiratory activity of specific cell types, such as splenic B cells. B cells are of relevance, as they play functional roles in obesity-induced insulin resistance, inflammation, and responses to infection. Here, we tested the hypothesis that high-fat-diet (HFD)-induced obesity could impair the mitochondrial respiration of intact and permeabilized splenic CD19+ B cells isolated from C57BL/6J mice and activated ex vivo with lipopolysaccharide (LPS). High-resolution respirometry was used with intact and permeabilized cells. To reveal potential mechanistic targets by which HFD-induced obesity dysregulates B cell mitochondria, we conducted proteomic analyses and 3D serial block face scanning electron microscopy (SBFEM). High-resolution respirometry revealed that intact LPS-stimulated B cells of obese mice, relative to controls, displayed lower ATP-linked, as well as maximal uncoupled, respiration. To directly investigate mitochondrial function, we used permeabilized LPS-stimulated B cells, which displayed increased H2O2 emission and production with obesity. We also examined oxidative phosphorylation efficiency simultaneously, which revealed that oxygen consumption and ATP production were decreased in LPS-stimulated B cells with obesity relative to controls. Despite minimal changes in total respiratory complex abundance, in LPS-stimulated B cells of obese mice, three of the top ten most downregulated proteins were all accessory subunits of respiratory complex I. SBFEM showed that B cells of obese mice, compared to controls, underwent no change in mitochondrial cristae integrity but displayed increased mitochondrial volume that was linked to bioenergetic function. Collectively, these results establish a proof of concept that HFD-induced obesity dysregulates the mitochondrial bioenergetic metabolism of activated splenic B cells.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Nutrients
Journal volume
  • 15
Journal issue
  • 22
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  • 4807
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  • English
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  • 2072-6643
Publisher
  • MDPI

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