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Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness

Xiaoxiao Peng1, Alfredo Giménez-Cassina1,2, Paul Petrus3

  • 1Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Scientific Reports
|June 28, 2016
PubMed

Insights

Thioredoxin reductase 1 (TrxR1) suppresses insulin response and fat cell development. Loss of TrxR1 enhances glucose and lipid metabolism, promoting adipogenesis and insulin sensitivity in mice and humans.

Area of Science:

  • Metabolic regulation
  • Cellular metabolism
  • Biochemistry

Background:

  • Thioredoxin reductase 1 (TrxR1) is implicated in glucose and lipid metabolism.
  • Its precise role in insulin responsiveness and adipocyte differentiation requires further elucidation.

Purpose of the Study:

  • To investigate the function of TrxR1 in regulating insulin responsiveness, anabolic metabolism, and adipocyte differentiation.
  • To determine the molecular mechanisms by which TrxR1 influences these processes.

Main Methods:

  • Utilized Txnrd1-deficient mouse embryonic fibroblasts (MEFs) to assess metabolic phenotypes.
  • Examined gene expression (PPARγ, p27, p53) and protein activation (Akt).
  • Performed TXNRD1 transcript knockdown in human primary preadipocytes and analyzed adipose tissue from women.

Main Results:

  • Txnrd1(-/-) MEFs exhibited increased metabolic flux, glycogen storage, lipogenesis, and adipogenesis.
  • Phenotype correlated with upregulated PPARγ, enhanced Akt activation, and altered cell cycle regulators (p27, p53).
  • TXNRD1 knockdown accelerated adipocyte differentiation in human cells; TXNRD1 levels inversely correlated with insulin sensitivity and lipogenesis in human adipose tissue.

Conclusions:

  • TrxR1 acts as a suppressor of anabolic metabolism and adipogenesis.
  • TrxR1 inhibits insulin signaling pathways, thereby regulating adipocyte differentiation and metabolic processes.
  • TrxR1 is a potential therapeutic target for metabolic disorders.

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