Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice

Abstract

Aim: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D).

Methods: Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA(1.5%) and SA(15%) , respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA(15%) groups.

Results: After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA(15%) group compared with the other groups showing a beneficial effect of SA on hyperglycaemia. During OGTT, plasma glucose area under the curve was reduced after SA(15%) compared with the other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA(15%) compared with Ctrl suggesting a reduced hepatic glucose output induced by SA.

Conclusion: Dietary supplementation of SA largely improves glycaemic control in a mouse model of T2D. This beneficial effect may be due to (i) an improved glucose-induced insulin secretion and (ii) a reduced hepatic glucose output.

Figure 1

Fasting blood glucose measured weekly during the study after a 6-h food deprivation. Open circle: Ctrl, black diamond: SA_1.5% and black square: SA_15%. ^*p value < 0.05, ^**p value < 0.01 as compared to control group.

Figure 2

Oral glucose tolerance test measurements performed at the end of the supplementation period: (A) blood glucose, (B) area under the curve (AUC) blood glucose, (C) plasma insulin and (D) insulin AUC. Open circle: Ctrl, black diamond: SA_1.5% and black square: SA_15%. ^*p value < 0.05, ^**p value < 0.01 as compared to control group.