The Combinatorial Effect of Acetate and Propionate on High-Fat Diet Induced Diabetic Inflammation or Metaflammation and
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ORIGINAL ARTICLE
The Combinatorial Effect of Acetate and Propionate on High-Fat Diet Induced Diabetic Inflammation or Metaflammation and T Cell Polarization Dipeeka K. Mandaliya,1 Sweta Patel,1 and Sriram Seshadri
1,2
Abstract— High-fat diet (HFD) alters the gut microbiota and its fermentation products mainly acetate, propionate, and butyrate. Butyrate is well studied as a regulator of host metabolism and inflammation while acetate and propionate still need to be studied. Therefore, we aim to decipher the role of acetate and propionate alone and in combination in HFD-induced diabetic mice. HFD was given to mice for 4 months followed by treatment of butyrate, acetate, and propionate as well as acetate + propionate in combination for 1 month. Diabetic outcome was confirmed by evaluating fasting glucose, lipid profile, oral glucose tolerance test, % HbA1c, fasting insulin, and glucagon. To check the immune response, spleen and mesenteric lymph node–specific T cell polarization and serum cytokine profile were studied. HFD-fed mice showed increased body weight and diabetic characteristics while treatment with acetate and propionate regulated their levels in a healthy manner similar to butyrate. In HFD-fed mice, Th1 and Th17 cells were increased while Treg cells were decreased along with increased pro-inflammatory cytokines and decreased IL-10 in serum. The T cell polarization and cytokine profile was reversed by the treatment of acetate and propionate alone and in combination. Acetate reduced the levels of IL-1β and IL-6 and acetate + propionate reduced IL-6 more significantly than butyrate. Although, we did not find any synergistic effect in combination group, the results were better compared with acetate, propionate, and butyrate. In conclusion, acetate + propionate effectively reduced inflammation and improved insulin sensitivity in HFD-induced diabetic mice. KEY WORDS: inflammation; T regulatory (Treg) cells; insulin resistance; type II diabetes (TIID); T cell polarization.
INTRODUCTION
Dipeeka K Mandaliya is the first author. 1 2
Institute of Science, Nirma University, Ahmedabad, Gujarat, India To whom correspondence should be addressed at Institute of Science, N i r m a Un i v e r si t y , A h m e da b a d, G uj a r at , I nd i a. E - ma i l: [email protected]
The gut microbiota influences host immunity and metabolism and is associated with various metabolic diseases such as obesity and diabetes. The gut microbiota are thought to interact with host via its fermentation products, i.e., short chain fatty acids (SCFAs) mainly acetate, propionate, and butyrate. Butyrate has been well studied for its anti-inflammatory potential in case of various
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Mandaliya, Patel, and Seshadri inflammatory diseases like inflammatory bowel disease, cancer, obesity, and diabetes. Butyrate regulates inflammation by influencing immune cell migration, adhesion, and inflammatory cytokine secretion [16]. Saemann et al. showed c
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