Soy Proteins Deficient in the α’ Subunit of β‐Conglycinin and Various Glycinin Subunits Maintain the Ability to Modulate Hepatic Lipid and Glucose Metabolism

Abstract

Soy consumption has been associated with improved blood lipid profiles and decreased incidence of metabolic diseases. However, the involved molecular mechanism(s) and the bioactive components in soy remain unclear. This study examined the effect of soy proteins with depletion of different subunits of the two major storage proteins, β‐conglycinin and glycinin, on hepatic lipids and proteins involved in lipid and glucose metabolism as well as inflammation in rats and cultured human hepatocytes. Sprague‐Dawley rats (8 males and 8 females/group) were fed diets containing either 20% casein or 20% conventional soy proteins or soy proteins depleted in different β‐conglycinin and glycinin subunits. After 8 weeks, the rats were necropsied for collection of blood and tissue samples. Human HepG2 liver cells were treated with casein or test soy protein hydrolysates in the media containing low (5 mM) or high (25 mM) levels of glucose with or without insulin and tumour necrosis factor alpha (TNF‐α). Hepatic lipids were extracted and measured. Various modulators of lipid and glucose metabolisms in the liver and cultured human hepatocytes were determined by Western blot. Serum inflammation markers were analysed by a magnetic beads‐based multiplexing immunoassay. The results showed that the soy diets lacking glycinins reduced hepatic lipid droplet formation, total cholesterol, triglycerides, and non‐esterified fatty acids content in the male rats compared to rats on the casein control diets, and a similar trend was observed in the females. The soy diets lacking glycinins significantly attenuated serum inflammation markers and the abundance of mature hepatic sterol regulatory element binding protein ‐1 (SREBP‐1) and fatty acid synthase (FAS) in both genders and decreased hydroxymethylglutaryl‐CoA reductase (HMGCR) and low‐density lipoprotein receptor (LDL‐R) in female livers. Soy protein hydrolysates devoid of glycinins significantly increased Akt phosphorylation in high glucose concentrations. These results suggest that the remaining soy protein components other than α’ subunit of β‐conglycinin and glycinin may be associated with the health benefits of soy intake such as hypolipidemic function, improved insulin signalling and suppression of inflammation.Support or Funding InformationThis research was supported by Health Canada, Grain Farmers of Ontario Research Fund and the partnership of Agriculture and Agri‐Food Canada/Canadian Field Crops Research Alliance DIAP Fund. C.C. is supported by the National Science and Engineering Research Council (NSERC) Visiting Fellowship in Canadian Government Laboratories.