Transplantation of adipose tissue lacking PAI-1 improves glucose tolerance and attenuates cardiac metabolic abnormalities in high-fat diet-induced obesity

ABSTRACT

Adipose tissue is an important metabolic organ, and transplantation of white adipose tissue plays crucial roles in glucose homoeostasis and energy metabolism. However, how adipose tissue affects glucose utilization is poorly understood. PAI-1-knockout (PAI-1KO) mice were previously shown to be resistant to a high-fat diet and obesity. We used microPET/CT (positron emission tomography/computed tomography), gene microarray, and biochemical assays to measure changes in systemic and myocardial glucose metabolism in mice subjected to transplantation of adipose tissue from PAI-1KO and wild-type mice. Here, we show that transplanting subcutaneous white adipose tissue (scWAT) from PAI-1KO mice into high-fat diet (HFD)-fed mice reduced levels of serum total cholesterol and triglycerides, and improved glucose tolerance in the HFD-fed mice. microPET/CT imaging revealed that cardiac glucose uptake was increased in the heart but not in the liver, hindlimb muscles, or abdominal subcutaneous white adipose tissue in HFD-fed mice transplanted with PAI-1KO scWAT, suggesting that the transplanted PAI-1KO scWAT exerted endocrine effects in the heart. In addition, transplantation of scWAT from PAI-1KO mice upregulated mitochondrial gene expression in cardiac muscle, increased the expression of glucose transporters 1 and 4 in cardiac tissues and was associated with an increased NAD⁺/NADH ratio. Together, these findings suggest that modulating PAI-1 in scWAT may provide a promising approach for intervening in glucose metabolism.

KEYWORDS:

• PAI-1
• transplantation
• adipose tissue
• glucose
• high-fat diet

Author contributions

S. L. and R. L. designed and performed experiments, analyzed data, and wrote the manuscript; Y. L., X. F., K. L., C. X., L. Z., M. L., and L. W. performed animal experiments; R. L., and J. W. designed and analyzed experiments and wrote the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplemental material

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Additional information

Funding

This work was supported by the National Natural Science Foundation of China Grant [81570263, 81402431].