Relationship between Carnitine, Fatty Acids and Insulin Resistance

Abstract

Increased plasma free fatty acid (FFA) levels are a feature of insulin resistance and type 2 diabetes. The aim of the present study was to assess the effect of L-carnitine supplementation on plasma lipids and the expression of enzymes in peripheral mononucleated cells (PMNC) involved in the regulation of fatty acid and glucose oxidation. L-Carnitine supplementation of 2 g/day resulted in a significant decrease in plasma FFA and in a less pronounced diminution of the plasma triacylglycerols. In addition, a concomitant increase in the relative mRNA abundances of carnitine acyltransferases (5- to 10-fold) and of the carnitine carrier OCTN2 (12-fold) in PMNC of pregnant women was found. The results of the present study provide evidence that L-carnitine supplementation in pregnancy (2 g/day) avoids a striking increase in plasma FFA, which are thought to be the main cause of insulin resistance and consequently gestational diabetes mellitus.

Lipid Composition of Cell Membranes and Its Relevance in Type 2 Diabetes Mellitus

“…Third, we looked at the relationship between GDM and type 2 diabetes [ 1 ]. One of the characteristics of the second half of pregnancy is an appreciable increase in the maternal plasma concentration of free fatty acids, which is thought to be the main cause of a decrease in insulin sensitivity and in the unsaturation index [ 57 - 59 ]. We suggest that a reduction in the unsaturation index in pregnant women with GDM is the summation of two indexes: the typical temporal decrease in index seen in late pregnancy, and a more chronic decrease seen in the prediabetic stage of type 2 diabetes mellitus (Fig.…”

“…Reductions in basal rates of mitochondrial ATP synthesis in skeletal muscle due to decreased mitochondrial activity or a relative short supply of ATP in maternal circulation during pregnancy because of foetal growth are early events [ 76 - 78 ] and serve to drive hepatic lipogenesis. This leads to a gradual elevation of plasma free fatty acids [ 58 , 59 , 79 - 81 ] to yield more energy (in the form of ATP), which develops a shift from unsaturated towards saturated fatty acyl chains of membrane phopholipids and a harmful increase in membrane stiffness which results in a reduction in both successful insertions of insulin-independent GLUTs into plasma membrane and fusions of insulin-dependent GLUT4 containing vesicles with plasma membrane. The net effect would be a decreased flux of glucose into cells which causes a further stimulus to hepatic fatty acid production.…”

Membrane Flexibility and Exercise: A Guide to Type 2 Diabetes Mellitus

“…Regarding the aetiology of type 2 diabetes mellitus, we recapitulate that already in the pre-diabetic phase, reductions in basal rates of mitochondrial ATP synthesis in skeletal muscle caused by decreased mitochondrial activity [15][16][17] serve to drive hepatic lipogenesis. This process leads to the gradual elevation of plasma free fatty acids [18,19] to yield more energy in the form of ATP, which develops a shift of membrane phospholipids from unsaturated fatty acyl chains toward saturated fatty acyl chains, resulting in decreased flexibility and consequently in a decreased flux of glucose into the cells. What is clinically exciting is that the regulation of membrane flexibility may reverse the incidence of type 2 diabetes in high-risk individuals.…”

Customized Nutritional Enhancement for Pregnant Women Appears to Lower Incidence of Certain Common Maternal and Neonatal Complications: An Observational Study

“…For example, maternal carnitine insufficiency treated with 2000 mg of carnitine avoids a striking rise in free fatty acids, which are thought to be the main cause of insulin resistance and gestational diabetes. 8 Because GDM is associated with LGA offspring and because these offspring experience a greater than average risk for adult disease, especially adult onset DM (AODM), it is reasonable to expect a reduced incidence of chronic disease if maternal carnitine insufficiency is recognized and treated. Iron status, more commonly assessed in pregnancy, is not only important in hematopoesis and neurological and cognitive development 9 but plays a crucial role in carnitine synthesis, 10 although carnitine precursors may be more important.…”