CHAMPAIGN, Ill. – A protein in soybeans blocks production of a liver enzyme involved in the metabolism of triglycerides and low-density lipoprotein, scientists found in a recent study.

Consuming soy flour rich in the protein B-conglycinin has the potential to reduce low-density lipoprotein – LDL – cholesterol levels and reduce the risk of metabolic diseases such as atherosclerosis and fatty liver disease, said Elvira de Mejia, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign.

Scientists have long known of soybeans’ cholesterol-reducing properties and lipid-regulating effects. Researchers in the recent project at the University of Illinois investigated two soy proteins thought to be responsible for the outcomes – glycinin and B-conglycinin. They found the latter to be particularly significant.

“Soybeans’ effects on cholesterol metabolism are associated with their protein concentrations and composition,” de Mejia said. “They’re also associated with peptides embedded in them that are released during gastrointestinal digestion.”

The team defatted and ground into flour 19 soybean varieties, each of which contained differing proportions of the two proteins. The proportion of glycinin in the varieties ranged from 22 percent to 60 percent. The proportion of the B-conglycinin ratio ranged from 22 percent to 52 percent.

Using a simulation of the human digestive process validated by other studies, the team sequentially mixed the defatted soybean flours with various fluids and enzymes to mimic the oral, gastric, intestinal and colonic phases of digestion. They identified 13 bioactive peptides produced during digestion, most of which came from glycinin and B-conglycinin.

When testing the digested materials’ capacity to inhibit the activity of HMGCR, a protein that controls the rate of cholesterol synthesis, the researchers found their inhibitory properties were two-to-seven times less potent than simvastatin, a drug used to treat high LDL cholesterol and fat levels in the blood. Simvastatin was used as a control in the study.

After classifying the soybean varieties by their glycinin and B-conglycinin composition and their HMGCR inhibitory properties, the team selected five varieties for further analysis.

“We started with cells that were already exposed to fatty acids to mimic fatty liver disease and tried to understand the role of the digested soy proteins,” de Mejia said. “We measured several parameters associated with cholesterol and lipid metabolism and various other markers – proteins and enzymes – that positively or negatively affect lipid metabolism.”

The markers included HMGCR and angiopoietin-like 3 – ANGPTL3 – a protein secreted primarily by the liver that’s a critical modulator of lipid metabolism, de Mejia said.

ANGPTL3 inhibits the enzymes involved in the metabolism of triglycerides, LDL cholesterol and high-density lipoprotein cholesterol, which is sometimes called “good cholesterol.” Both HMGCR and ANGPTL3 are overexpressed in fatty liver disease, the researchers found.

Secretion of ANGPTL3 more than tripled after the liver cells were exposed to the fatty acids, de Mejia said. But the team found that peptides from three of the digested soybean varieties reduced ANGPTL3 secretion by 41 percent to 81 percent in correlation with their glycinin and B-conglycinin ratios.

Although the fatty acids reduced the liver cells’ absorption of LDL cholesterol by more than one-third, the soybean digests reversed that by inhibiting the expression of a protein. The digests increased the cells’ uptake of LDL by 25 percent to 92 percent, depending on the soybean variety and its glycinin and B-conglycinin proportions.

“One of the key risk factors of atherosclerosis is oxidized LDL cholesterol so we investigated the preventive effects of the soybean digests at eight different concentrations,” de Mejia said. “Each of them reduced the LDL oxidation rate in a dose-dependent manner, inhibiting formation of both early and late oxidation products associated with the disease.”

Greater concentrations of B-conglycinin in the digests correlated with larger reductions in oxidized LDL, esterified cholesterol, triglycerides and HMGCR levels in plasma.

“The digested soybeans’ peptides were able to reduce lipid accumulation by 50 percent to 70 percent,” de Mejia said. “That was comparable to the statin, which reduced it by 60 percent. We also saw different markers influenced by key enzymes that regulate hepatic lipogenesis – the development of a fatty liver.”

ANGPTL3’s circulating levels are associated with relatively high hepatic impairment and inflammation, de Mejia said.

“Our role as food scientists is to find bioactive compounds that could regulate this in plasma," she said. "It’s easy to measure to prevent hyperlipidemia and atherosclerosis."

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