Do you know the sweetest of all natural sugars? The answer is fructose. Fructose was once highly praised as a “healthy sugar” because it was sweeter and had a lower glycemic index than other natural sugars.
but is fructose really that healthy? Not necessarily. Because it may be a driver of nonalcoholic steatohepatitis. In population studies, fructose intake is associated with increased liver fat, inflammation and fibrosis . Its ability to cause liver fat accumulation is several times that of glucose, and Nash is an important cause of liver cancer.
but researchers have never known how fructose does this. In a recent journal, researchers at the University of California, San Diego, found the mechanism .
it turns out that after a large amount of fructose enters the intestinal tract and is decomposed by fructokinase, it will cause endoplasmic reticulum stress and intestinal inflammation, resulting in intestinal barrier damage, bacterial escape, and then endotoxemia. The increased pro-inflammatory cytokines will induce lipid synthesis, accumulation and degeneration in the liver, thus promoting the occurrence of NASH.
in this study, the researchers first fed genetically engineered Nash mice with a high fructose diet, while the control group used a corn starch diet with the same total energy, and 70% of the energy came from corn starch.
the intake of mice in the two groups was similar. The high fructose group quickly showed significant liver steatosis and increased triglyceride levels, while the corn starch group did not. At 6 months, insulin resistance, steatohepatitis and liver fibrosis were observed in the high fructose group. After 12 months, the liver tumor in the high fructose group was 3 times larger than that in the corn starch group, and the tumor load was 10 times higher.
in addition, the colon of mice became shorter, indicating that there was intestinal mucosal inflammation. In addition, long-term high fructose diet also led to the damage of intestinal barrier, which was mainly manifested in the decrease of mrma level of tight junction protein and the decrease of tight junction protein. This protein is the link between cells and forms the intestinal barrier together with intestinal epithelial cells.
intestinal mucositis is one of the reasons for the decrease of tight junction protein , and what causes intestinal mucositis? They found that similar to genetic factors leading to fructose intolerance, fructose-1-phosphate, a fructose metabolite, interferes with N-glycosylation, and N-glycosylation defects trigger endoplasmic reticulum stress. The levels of several markers related to endoplasmic reticulum stress in mice increased significantly, which led to intestinal mucosal inflammation and impaired the assembly of tight junction proteins.
after the intestinal barrier was damaged, the intestinal microflora of mice escaped from the intestinal tract. Blood tests showed that endotoxemia occurred in mice. Antibiotic treatment could almost completely inhibit endotoxemia, prevent hepatic steatosis and reduce the occurrence of liver tumor.
by comparing the liver and inflammation related transcriptome of mice in high fructose group and corn starch group at different stages, the researchers found that in 9-month-old mice, the expression level of liver cancer-related specific genes increased, and the expression of genes related to wound healing, cell adhesion and innate immunity also changed significantly in 9-month-old mice.
further studies showed that the phosphorylation levels of Toll like receptor 2 and toll like receptor 4, which are related to innate immunity, increased in the liver of mice in high fructose group, and this change would disappear when treated with antibiotics. Their increased expression is most likely to occur in macrophages recruited from the liver.
activated macrophages are the main source of pro-inflammatory factors and tumor necrosis factors. In vitro culture of human primary hepatocytes, it has been shown that the hepatocytes co cultured with fructose will have stronger accumulation of lipid droplets when treated with endotoxin and TNF, and this can not be achieved if only lipopolysaccharide and no TNF.
that is to say, fructose induced intestinal barrier damage and endotoxemia are mediated by TNF secreted by macrophages.
supplement of IL-6 mediated by integrin can promote the repair of tight junction protein through matrix protein CCN1, or activate gp130 signal of intestinal epithelium, and promote repair through stat and Yap pathway. The integrity of the intestinal barrier is guaranteed, which also inhibits bacterial escape and endotoxemia caused by high fructose diet.
these mice successfully resisted the occurrence of liver tumor induced by fructose, and the mRNA expression of genes related to inflammation and lipid synthesis did not increase significantly.
researchers said that in the United States, one third of people suffer from nonalcoholic fatty liver disease. Although a certain amount of fructose a day will not cause obvious harm, only long-term excessive intake will, but the reality is that many processed foods contain fructose, and most people can’t estimate how much fructose they actually eat.
they believe that, on the one hand, it is necessary to improve people’s understanding of the harm of fructose overdose, and on the other hand, for patients with fatty liver disease who have developed into fatty liver disease, the treatment based on intestinal barrier repair may be a new potential treatment.
original title: sub issue: fructose promotes fecal bacteria to enter blood! Scientists have found that excessive fructose can cause intestinal barrier damage, increase inflammation, and promote fat deposition and degeneration in the liver=“ https://luanban.com/category/focus/#content ” target=”_ blank” rel=”noopener”>Skip to content