Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice

Samantha L. Hocking, Rebecca L. Stewart, Amanda E. Brandon, Eurwin Suryana, Ella Stuart, Emily M. Baldwin, Ganesh A. Kolumam, Zora Modrusan, Jagath R. Junutula, Jenny E. Gunton, Michael Medynskyj, Sinead P. Blaber, Elisabeth Karsten, Benjamin R. Herbert, David E. James, Gregory J. Cooney, Michael M. Swarbrick*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    38 Citations (Scopus)

    Abstract

    Aims/hypothesis Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood.

    Methods We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks.

    Results Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations.

    Conclusions/interpretation Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.

    Original languageEnglish
    Pages (from-to)1587-1600
    Number of pages14
    JournalDiabetologia
    Volume58
    Issue number7
    DOIs
    Publication statusPublished - Jul 2015

    Keywords

    • Adipose tissue
    • Body fat distribution
    • Fatty liver
    • Glucose intolerance
    • Inflammation
    • Insulin resistance
    • Intra-abdominal fat
    • Obesity
    • Subcutaneous fat
    • Visceral

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