Effects of short chain fatty acids on metabolism of glucose and lipid in obese mice induced by high fat diet

Abstract

Abstract: Objective To observe the effects of short chain fatty acids (SCFAs) on metabolism of glucose and lipid in obese mice induced by high fat diet (HFD), and to investigate the possible mechanisms from the perspective of intestinal epithelial barrier function. Methods Forty C57BL/6J mice were equally randomly divided into normal diet (ND) group, HFD model group, SCFAs treatment (HFD+SCFAs) group and lactulose (LA) treatment (HFD+LA) group. Mice were fed a HFD for 14 weeks, and treated with corresponding drugs or distilled water since week 10. After 4-week treatment, mice were sacrificed for observing body weight, food intake, liver weight, ratio of liver weight to body weight, morphology and diameter of adipocytes after epididymis, fasting plasma glucose (FBG), fasting serum insulin (FINS), homeostatic model assessment insulin resistance (HOMA-IR), serum triglyceride (TG), serum cholesterol (TC), low density lipoprotein, hepatic TG, serum alanine aminotransferase, aspartate aminotransferase, and hepatic and colonic tissue pathological changes. Results The body weight, liver weight, ratio of liver weight to body weight, FBG, FSI, HOMA-IR, serum TG, serum TC and hepatic TG in HFD+SCFAs group were significantly lower than those in the HFD group (P<0.01). SCFAs was superior to LA in reducing FSI, HOMA-IR, serum TG, serum TC, and hepatic TG (P<0.01 or P<0.05). Moreover, hepatic steatosis, inflammation and ballooning were significantly improved in HFD+SCFAs group than those in HFD group, and disease activity score was decreased (P<0.01). SCFAs intervention could significantly improve colonic pathology, including colonic epithelial damage, glandular disorder and inflammatory cell infiltration induced by HFD. Conclusion SCFAs can effectively reduce body weight, improve the metabolism of glucose and lipid and decrease hepatic fat deposition in obese mice induced by HFD. Reducing intestinal inflammatory response and enhancing intestinal epithelial barrier function maybe one of the possible mechanisms.

Key words: Short chain fatty acids, Obesity, Metabolism of glucose and lipid, Fatty liver

LIU Qian, CHENG Chen, XIN Xin, HU Yi-yang, FENG Qin. Effects of short chain fatty acids on metabolism of glucose and lipid in obese mice induced by high fat diet[J]. Chinese Hepatolgy, 2018, 23(7): 591-595.

References

[1] Maruvada P, Leone V, Kaplan LM, et al. The Human Microbiome and Obesity: Moving beyond Associations.Cell Host Microbe, 2017,22: 589-599.
[2] 杨蕊旭,周达,范建高.靶向肠道菌群代谢产物防治非酒精性脂肪性肝病.实用肝脏病杂志,2017, 20: 643-646.
[3] Tan J, McKenzie C, Potamitis M, et al. The role of short chain fatty acids in health and disease. Adv Immunol, 2014,121:91-119.
[4] Chambers ES, Viardot A, Psichas A, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut, 2015,64: 1744-1754.
[5] Lin HV, Frassetto A, Kowalik EJ, Jr., et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One, 2012,7: e35240.
[6] den Besten G, Bleeker A, Gerding A, et al. Short-Chain Fatty Acids Protect Against High-fat Diet-induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation. Diabetes, 2015,64: 2398-2408.
[7] Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 2005,41: 1313-1321.
[8] Brown JM, Hazen SL. Targeting of microbe-derived metabolites to improve human health: The next frontier for drug discovery.J Biol Chem, 2017,292: 8560-8568.
[9] Barroso E, Montilla A, Corzo N, et al.Effect of lactulose-derived oligosaccharides on intestinal microbiota during the shift between media with different energy contents. Food Res Int, 2016,89: 302-308.
[10] Schachter J, Martel J, Lin CS, et al.Effects of obesity on depression: Arole for inflammation and the gut microbiota.Brain Behav Immun, 2017,S0889-1591: 30415-30424.
[11] Chen T, Kim CY, Kaur A, et al.Dietary fibre-based SCFAmixtures promote both protection and repair of intestinal epithelial barrier function in a Caco-2 cell model.Food Funct, 2017,8: 1166-1173.