Matt's mapping is actively involved in various metabolomics clinical studies and is dedicated to precision medicine based on metabolomics. Recent studies have found that elevated levels of free fatty acids can lead to insulin resistance through increased lipid metabolites, increased release of inflammatory factors, endoplasmic reticulum stress, and oxidative stress. Insulin resistance is closely related to T2DM, hypertension, and dyslipidemia.
Studies have also found that bile acids not only play a role in nutrient absorption, but are also important signaling molecules that activate signaling pathways and regulate gene expression by activating bile acid receptors, in bile acid metabolism, lipid metabolism, glucose metabolism, and energy homeostasis. It plays an important role. But with the development of obesity and its associated diabetes, changes in bile acid levels and their interaction with fatty acids are still not well understood.
In order to clarify the effects of the interaction of fatty acids and bile acids on the metabolism of obese individuals, the study used the targeted metabolomics method of Meite's mapping, including 199 normal people, 78 overweight/obese patients and A case-control study of 66 patients with overweight/obese T2DM and quantitative metabolic testing and systematic analysis of serum bile acid and fatty acid profiles in obese diabetic patients undergoing metabolic surgery. Further possible mechanisms are elucidated by animal and cell experiments.
Significance of serum fatty acids in obesity-related metabolic diseases
Insulin resistance is the core of the pathogenesis of type 2 diabetes. Free fatty acids are closely related to the development of obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. Long-term exposure to high concentrations of fatty acids, insulin function of islet β cells will be impaired, resulting in lipotoxic effects. High levels of fatty acids in the circulation exceed the storage capacity of adipose tissue and the ability of peripheral tissues to oxidize fatty acids. Excess free fatty acids are deposited in the form of triglycerides in non-adipose tissues such as myocytes, hepatocytes and islet beta cells. This results in insulin resistance, nonalcoholic fatty liver disease and type 2 diabetes.
Therefore, changes in fatty acid levels are important features of obesity-related metabolic syndrome and cardiovascular disease. Systematic analysis of changes in fatty acid levels in metabolic disease populations is important for disease risk prediction, early diagnosis and treatment.
Significance of serum bile acids in obesity-related metabolic diseases
Bile acid is synthesized in the liver and is the main way to clear cholesterol in the body. After eating, bile acids are secreted into the small intestine, which digest and absorb lipids and fat-soluble vitamins. Bile acids not only play a role in nutrient absorption, but also serve as important signaling molecules that play important roles in sugar metabolism, lipid metabolism, and energy homeostasis by activating different bile acid receptors.
Activation of the bile acid membrane receptor can promote the release of GLP-1 from intestinal endocrine cells, thereby exerting effects on the regulation of glucose metabolism and insulin sensitivity. In addition, it is also possible to increase the activity of brown fat cells in humans and animals, resulting in an increase in energy expenditure, thereby inhibiting the occurrence of obesity. Activation of bile acid nuclear receptors can inhibit hepatic gluconeogenesis, increase insulin sensitivity in peripheral tissues such as muscle and fat, and also induce insulin release from islet beta cells in the second phase. On the other hand, its activation inhibits the synthesis of fatty acids and triglycerides in the liver, regulates the expression of lipoprotein and fatty acid uptake genes, and induces an increase in fatty acid oxidation. Therefore, the search for changes in bile acid levels and composition is of great significance for the prevention and treatment of metabolic diseases such as obesity, type 2 diabetes, and nonalcoholic fatty liver.
The ratio of di- gamma- linolenic acid to deoxycholic acid bile acid is a molecular marker of metabolic abnormality in obese individuals.
The study found that compared with non-diabetic patients, the serum bile acid profile of DCA species decreased significantly and was significantly associated with clinical indicators; serum free fatty acids were significantly elevated, especially some polyunsaturated Fatty acids, of which di-high-gamma-linolenic acid (DGLA) is the most prominent, have the strongest correlation with various clinical indicators. Moreover, there was a significant negative correlation between the two, and the ratio of DGLA/DCA species gradually increased with obesity and diabetes. In patients undergoing metabolic surgery, both DCA species and DGLA had significant outcomes, and the ratio was also significantly reduced. In addition, the ratio is significantly correlated with various clinical indicators. The results of the study on the liver tissue of mice with obesity and impaired glucose tolerance induced by high-fat diet are consistent with the human body, suggesting that the changes in the circulation may be caused by abnormal metabolism of liver tissue. Furthermore, we have studied liver cells and found that DCA and its tauro-binding TDCA may affect DGLA metabolism by inhibiting the fatty acid uptake gene FATP5. Therefore, this study demonstrates that abnormalities in bile acid and fatty acid metabolism and their interactions cause obesity-related metabolic disorders. The ratio of DGLA/DCA species can well reflect the metabolic status of unhealthy obesity and can serve as a potential molecular marker for metabolic abnormalities in overweight or obese patients. The findings were recently published in the international academic journal The FASEB Journal.
Document source
1. Lei, S., Huang, FJ, Zhao, A. H, Chen, TL, Chen, W. L, Xie, G. X, Zheng, XJ, Zhang, YJ, Yu, HY, Zhang, P., Rajani, C., Bao, YQ, Jia, WP, Jia, W. The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity. FASEB J. 2017, 31.
2. Geoffrey Porez, Janne Prawitt, Barbara Gross, Bart Staels. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease, J Lipid Res. 2012, 53(9): 1723–1737.
3. Mi-Jeong Lee, Yuanyuan Wu, Susan K. Fried. Adipose Tissue Heterogeneity: Implication of depot differences in adipose tissue for Obesity Complications. Mol Aspects Med, 2013, 34(1): 1–11.
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