Safflower yellow improves insulin sensitivity in high-fat diet-induced obese mice by promoting peroxisome proliferator-activated receptor-γ2 expression in subcutaneous adipose tissue

J Diabetes Investig. 2020 Nov;11(6):1457-1469. doi: 10.1111/jdi.13285. Epub 2020 Jun 5.

Abstract

Aims/introduction: Safflower yellow (SY) and its main component, hydroxysafflor yellow A, have been demonstrated to show anti-obesity effects. Peroxisome proliferator-activated receptor-γ2 (PPARγ2) is a critical transcription factor in adipose tissue metabolism. The aim of the present study was to explore the effects of SY in high-fat diet-induced obese mice, and further investigate the mechanism involving PPARγ2.

Methods: High-fat diet-induced obese mice were given 120 mg/kg/day SY for 8 weeks. Glucose and insulin tolerance tests were carried out. Fat mass and serum levels of glucose and insulin were measured. The expression of insulin signaling pathway-related genes and PPARγ2 in the adipose tissue was measured. In vitro, the effects of SY (0-500 mg/L) and hydroxysafflor yellow A (0-100 mg/L) on PPARγ2 promoter activities and PPARγ2 messenger ribonucleic acid (mRNA) levels in 3T3-L1 preadipocytes or adipocytes were also detected.

Results: Safflower yellow reduced fat mass, decreased glucose levels and improved insulin sensitivity in obese mice. SY also increased the mRNA levels of insulin signaling pathway-related genes, and increased PPARγ2 mRNA levels by 39.1% in subcutaneous adipose tissue (P < 0.05). In vitro, SY and hydroxysafflor yellow A significantly enhanced PPARγ2 promoter activities by 1.3-2.1-fold, and increased PPARγ2 mRNA levels by 1.2-1.6-fold in 3T3-L1 preadipocytes or adipocytes (P < 0.05).

Conclusions: SY could reduce fat mass, decrease glucose levels and improve insulin sensitivity in high-fat diet-induced obese mice. The probable mechanism is to increase PPARγ2 expression by stimulating PPARγ2 promoter activities, further increasing the expression of insulin signaling pathway-related genes in subcutaneous adipose tissue.

Keywords: Obesity; Peroxisome proliferator-activated receptor-γ2; Safflower yellow.

MeSH terms

  • Animals
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology
  • Diet, High-Fat
  • Gene Expression Regulation*
  • Insulin Resistance*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Obese
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Obesity / pathology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Subcutaneous Fat / drug effects*
  • Subcutaneous Fat / metabolism
  • Subcutaneous Fat / pathology

Substances

  • PPAR gamma
  • safflower yellow
  • Chalcone