Soy protein compared with whey protein ameliorates insulin resistance by regulating lipid metabolism, AMPK/mTOR pathway and gut microbiota in high-fat diet-fed mice

Abstract

The findings of soy protein <i>versus</i> whey protein supplementation on glycemic regulation are inconsistent. The aim of the present study was to investigate the preventive effect of soy protein isolate (SPI) and whey protein isolate (WPI) on a high-fat diet (HFD) induced insulin resistance and its potential molecular mechanisms. Male C57BL/6J mice were randomly divided into seven groups (<i>n</i> = 12): normal control, HFD plus 10% SPI, HFD plus 20% SPI, HFD plus 30% SPI, HFD plus 10% WPI, HFD plus 20% WPI, and HFD plus 30% WPI. After 12 weeks of feeding, compared with the WPI groups, serum concentration of insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and liver weight were significantly lower in the SPI groups. Compared with the WPI groups, the mRNA levels of <i>CD36</i>, <i>SLC27A1</i>, <i>PPARγ</i> and <i>AMPKα</i> were significantly higher, and those of <i>LPL</i>, <i>SREBP1c</i>, <i>FASN</i> and <i>ACC1</i> were significantly lower in the liver in the SPI groups. In the liver or gastrocnemius muscle, compared with the WPI groups, the mRNA levels of <i>GLUT4</i>, <i>IRS-1</i>, <i>PI3K</i> and <i>AKT</i> were significantly higher, and those of <i>mTOR</i> and <i>S6K1</i> were significantly lower, and the protein levels of GLUT4, p-AMPKα/AMPKα, p-PI3K/PI3K and p-AKT/AKT were significantly higher, and those of p-IRS-1^Ser307/IRS-1, p-mTOR/mTOR and p-S6K1/S6K1 were significantly lower in the SPI groups. The Chao1 and ACE indices were higher, and the relative abundance of <i>Staphylococcus</i> and <i>Weissella</i> was lower in the SPI groups than those in the WPI groups. In conclusion, soy protein was more effective than whey protein in preventing IR in HFD-fed mice by regulating lipid metabolism, the AMPK/mTOR pathway, and gut microbiota.