Depot-specific adipocyte-extracellular matrix metabolic crosstalk in murine obesity

ABSTRACT

Subcutaneous (SAT) and visceral (VAT) adipose tissues have distinct metabolic phenotypes. We hypothesized that the extracellular matrix (ECM) regulates depot-specific differences in adipocyte metabolic function in murine obesity. VAT and SAT preadipocytes from lean or obese mice were subject to adipogenic differentiation in standard 2D culture on plastic tissue culture plates or in 3D culture in ECM, followed by metabolic profiling. Adipocytes from VAT relative to SAT manifested impaired insulin-stimulated glucose uptake and decreased adipogenic capacity. In 3D-ECM-adipocyte culture, ECM regulated adipocyte metabolism in a depot-specific manner, with SAT ECM rescuing defects in glucose uptake and adipogenic gene expression in VAT adipocytes, while VAT ECM impaired adipogenic gene expression in SAT adipocytes. These findings demonstrate that ECM-adipocyte crosstalk regulates depot-specific differences in adipocyte metabolic dysfunction in murine obesity.

KEYWORDS:

• Adipocyte
• extracellular matrix
• depot
• visceral
• subcutaneous
• adipose tissue
• obesity
• adipogenesis
• insulin resistance
• glucose uptake

Acknowledgments

The University of Michigan Microscopy/Image Analysis Laboratory performed scanning electron microscopy analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Institutes of Health [R01DK090262]; U.S. Department of Veterans Affairs (US) [I01CX001811]; National Institutes of Health (US) [R01DK115190].