Abstract
Purpose : To further explore the effect of 5-aminosalicylic acid (5-ASA) treatment on lipid levels in mice fed different diets. Methods: Groups of 9 - 10 mice each were randomly assigned to 6 different diets, low-fat diet (LFD) with or without 5-ASA, high-fat diet (HFD) with or without 5-ASA, and high-fat high-cholesterol diet (HFC) with or without 5-ASA for 12 weeks. Results: There were changes in gut microbiota of 5-ASA-treated mice, although gut permeability was similar between treated and non-treated groups. The level of fasting blood glucose, fasting plasma insulin and the curve of glucose tolerance test (GTT) in mice fed LFD, HFD or HFC diet were not affected by 5-ASA treatment. Although plasma lipid levels were similar between 5-ASA consuming and non-5-ASA groups in mice fed LFD and HFD, improved lipid profile was seen in mice that received HFC+5-ASA when compared with mice fed only HFC. Conclusion: These results indicate that targeting gut inflammation and dysbiosis with 5-ASA neither improves gut barrier nor insulin resistance (IR). Thus, results from therapies for metabolic disorder based on anti-gut inflammation should be interpreted with caution. Keywords : 5-Aminosalicylic acid, Small intestine, High-fat, High-cholesterol diet, Dyslipidemia, Glucose tolerance
Highlights
Obesity is emerging as one of the most harmful global public health problem
All the mice were able to access to food and water freely. They were randomly assigned to 6 groups, each having 10 mice, and fed either lowfat diet (LFD; the diet supplier is USA Research Diets, 10 % of energy coming from fat), low-fat diet (LFD) + 5-aminosalicylic acid (5ASA), high-fat diet (HFD; the diet supplier is USA Research Diets, 60 % of energy coming from fat ), HFD+5-aminosalicylic acid (5-ASA), high-fat high-cholesterol diet (HFC; the diet supplier is USA Research Diets, 60 % of energy coming from fat and plus 0.25 % cholesterol) or HFC+5-ASA for 12 weeks. 5-ASA powder (Sigma-Aldrich, USA) was mixed homogenously with LFD, HFD and HFC diets as appropriate, and presented at 1,500 mg/kg/day
Reverses insulin resistance (IR) through improvement of fasting blood glucose, insulin levels and glucose tolerance [21]. These are at variance with the data acquired in this study, which showed that 5ASA treatment did not have a specific effect on fasting blood glucose levels, fasting plasma insulin levels and glucose tolerance test (GTT) response in mice fed either LFD, HFD or HFC
Summary
The disease is associated with a series of metabolic complications, including insulin resistance (IR), and type 2 diabetes (T2DM), dyslipidemia. Numerous studies show that systemic inflammatory reaction has a vital role in the early stage of obesity and promotes obesityassociated complications [1,2,3]. Several conditions lead to systemic inflammation, and in recent years, gut inflammation and gastrointestinal flora have attracted more attention than ever before due to their relationship with the immune system and IR. High fat diet (HFD) is reported to induce lowgrade intestinal inflammation and dysbiosis of gut microbiota [7,8]. Intestinal inflammation and dysbiosis are believed to be related to broken and dysfunction of the intestinal wall, which may activate and further prompt systemic IR
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