J Bioenerg Biomembr. , 2020., doi: 10.1007/s10863-020-09859-z.

Effect of alpha linolenic acid on membrane fluidity and respiration of liver mitochondria in normoglycemic and diabetic Wistar rats

Mejia-Zepeda, R Perez-Hernandez, IH

Abstract

The omega 3 fatty acids (ω3FA) have been recommended for the treatment of Type 2 Diabetes Mellitus (T2DM) and its complications, but there are studies questioning those beneficial effects. In this research, we supplemented the short-chain ω3FA, alpha-linolenic acid (ALA), to a model of rats with T2DM and normoglycemic controls, for 5 months. We were mainly interested in studying the effects of diabetes and ALA on the physicochemical properties of mitochondrial membranes and the consequences on mitochondrial respiration. We found that the Respiratory Control (RC) of diabetic rats was 46% lower than in control rats; in diabetic rats with ALA supplement, it was only 23.9% lower, but in control rats with ALA supplement, the RC was 29.5% higher, apparently improving. Diabetes also decreased the membrane fluidity, changed the thermotropic characteristics of membranes, and increased the proportion of saturated fatty acids. ALA supplement partially kept regulated the physicochemical properties of mitochondrial membranes in induced rats. Our data indicate that diabetes decreased the membrane fluidity through changes in the fatty acids composition that simultaneously affected the RC, which means that the mitochondrial respiration is highly dependent on the physicochemical properties of the membranes. Simultaneously, it was followed the effects of ALA on the progress of diabetes and we found also that the supplementation of ALA helped in controlling glycaemia in rats induced to T2DM; however, in control non-induced rats, the supplementation of ALA derived in characteristics of initial development of diabetes.

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Key Points

In this research, the effects of 5 months supplementation of  ALA, on the physicochemical properties of liver mitochondrial membranes, and its respiration in rats induced to T2DM and in normoglycemic rats.

ALA has been associated with higher plasma insulin concentrations and lower plasma glucose concentrations. In pancreatic beta cells it has been shown that ALA, as well as other essential fatty acids like the linoleic acid, can induce insulin secretion similar to glucose and arginine.

If ALA promotes insulin synthesis or release from pancreatic beta cells, it explains the results obtained here. In rats induced to T2DM with streptozotocin, due to the reduced population of pancreatic beta cells, there are lower amounts of insulin but the use of ALA promotes their synthesis and release, normalizing the glycaemia, weight gain, cholesterol, and triglycerides. In conclusion, in this research it was found that the liver mitochondrial respiration is a metabolic process closely related to the physicochemical properties of the membranes, particularly the membrane fluidity and the fatty acids composition. It was also found that the development of diabetes decreased the membrane fluidity, as well as the U/S fatty acids ratio, and the mitochondrial RC. Treatment of rats induced to diabetes with ALA, kept the physicochemical properties of the membranes close to normal and the RC too.

It was concluded that the possible beneficial effects of ALA are dependent of the physiological condition of the subjects. In diabetic rats deficient in insulin, ALA may have a beneficial effect very likely derived from promotion of insulin synthesis and release, but in normoglycemic rats, the chronical intake of ALA may drive to hyperinsulinemia and an eventual development of diabetes by insulin resistance.