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Safflower Yellow Improves Insulin Sensitivity In High-Fat Diet-Induced Obese Mice By Promoting Peroxisome Proliferator-Activated Receptor-Gamma 2 Expression In Subcutaneous Adipose Tissue

JOURNAL OF DIABETES INVESTIGATION(2020)

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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-gamma 2 (PPAR gamma 2) 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 PPAR gamma 2.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 PPAR gamma 2 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 PPAR gamma 2 promoter activities and PPAR gamma 2 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 PPAR gamma 2 mRNA levels by 39.1% in subcutaneous adipose tissue (P < 0.05). In vitro, SY and hydroxysafflor yellow A significantly enhanced PPAR gamma 2 promoter activities by 1.3-2.1-fold, and increased PPAR gamma 2 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 PPAR gamma 2 expression by stimulating PPAR gamma 2 promoter activities, further increasing the expression of insulin signaling pathway-related genes in subcutaneous adipose tissue.
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Key words
Obesity, Peroxisome proliferator-activated receptor-gamma 2, Safflower yellow
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