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% (SA1.5% and SA15%, 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 SA15% groups.Results: After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA15% 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 SA15% 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 SA15% 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.

The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells

“…(Membrez et al . ). Consequently, SH‐SY5Y cells were exposed, in an identical manner to the incubations involving C10, to sebacic acid.…”

“…This latter process generates the dicarboxylic acid form of C10, sebacic acid, which has been shown to exhibit biological activity including improving glucose tolerance (Membrez et al . ). In contrast to such studies, sebacic acid in our experimental system showed no effect which again suggests the specificity of C10 with regards to causing mitochondrial proliferation.…”

Use of dicarboxylic acids in type 2 diabetes

“…When the diet of db/db mice was supplemented with 15% of the energy deriving from sebacic acid over a period of 6 weeks, glycaemic control was significantly improved in comparison with the control group [37]. Indeed, fasting plasma glucose and glycated haemoglobin dropped to Dicarboxylic acids for type 2 diabetes values 40 and 25%, respectively, lower than in control animals (P < 0.01) and became comparable to that of lean healthy db/+ animals.…”

Whole Grain Consumption Increases Gastrointestinal Content of Sulfate-Conjugated Oxylipins in Pigs − A Multicompartmental Metabolomics Study

“…Higher plants, such as rye and other grains, are natural sources of dicarboxylic acids, and the increased gastrointestinal content is therefore most likely derived from the microbial fermentation of the aleurone matrix. In addition, increased urinary secretion of dicarboxylic acids has been described in response to rye rich diets. , The role of dicarboxylic acids in human nutrition remains to be elucidated in further detail; however, oral supplementation of sebacic acid in type-2 diabetic mice have been shown to improve glycemic control by increasing insulin-mediated glucose clearance and reducing fasting plasma glucose concentrations compared to control animals . An increased intake of rye resulting in increased absorption of dicarboxylic acids could therefore partly explain the beneficial effects of rye on insulin sensitivity.…”