The Δ9 Fatty Acid Desaturation Index as a Predictor of Metabolic Disease

Abstract

There is a tremendous need for improved biomarkers that can be used in the clinical setting to aid in the early detection of metabolic diseases. Of particular interest is the metabolic syndrome, or insulin resistance syndrome, a condition that is often clinically diagnosed as a cluster of risk factors including abdominal obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, impaired glucose tolerance, and increased fasting glucose (1)(2). This constellation of phenotypes greatly increases the risk for the development of chronic conditions such as diabetes and several cardiovascular diseases. The root cause of the metabolic syndrome is insulin resistance, a condition in which the pancreas increases insulin secretion to compensate for the decreased ability of insulin-sensitive tissues to perform insulin-stimulated glucose uptake to maintain euglycemia (1). Therefore, the development of new tests that focus on the early detection of insulin resistance could help identify at-risk patients so that the benefits of lifestyle and pharmacological interventions can be maximized and progression to overt metabolic disease can be prevented. Insulin resistance is not limited to defects in carbohydrate metabolism, but is also associated with major perturbations in lipid metabolism (2). For example, adipocytes increase the release of free fatty acids (FFA)1 into the circulation, resulting in subsequent FFA uptake by the liver and other peripheral tissues, processes that may further exacerbate insulin resistance (2)(3). Although hepatic insulin resistance contributes to hyperglycemia by causing an inappropriate elevation in hepatic glucose production, the branch of insulin signaling responsible for stimulating de novo fatty acid biosynthesis in the liver remains intact (2)(4). Additionally, high-carbohydrate diets, especially those enriched in rapidly absorbed refined carbohydrates such as glucose and fructose, are able to potently stimulate de novo lipogenesis (DNL) (5). The effects of insulin and dietary carbohydrate occur via the transcriptional activation of …