Estimated Stearoyl-CoA-desaturase (SCD)-1 and Elongase of Very Long Chain Fatty Acids (Elovl) 6 Activities From Serum Fatty Acids Are Reciprocally Associated with Visceral Fat Area in Type 2 Diabetic Patients

Abstract

Introduction: Abdominal visceral fat accumulation can cause insulin resistance in type 2 diabetic patients. We investigated the association between serum fatty acid levels and the visceral fat area (VFA). Materials and methods: In this retrospective study we evaluated relationship between the serum levels of 24 fatty acids and the abdominal VFA measured by computed tomography in 32 patients with type 2 diabetes who had been hospitalized. Results: Of the 24 fatty acids evaluated, the serum palmitoleic acid (C16:1 n-7) level had a moderate positive correlation (r = 0.565) with VFA while the serum arachidic acid (C:20:0) level had a very weak negative correlation (r = -0.351);no significant correlations with the VFA were found for the remaining 22 fatty acids. On the other hand, we discovered 5 significant correlations in 18 estimated activity indices of elongases and desaturases, which were calculated with ratios of corresponding fatty acid concentrations. The palmitoleic acid (C16:1 n-7) /palmitic acid (C16:0) (r = 0.719, stearoyl-CoA-desaturase (SCD)-1 (16)) index and the oleic acid (C18:1 n-9) / stearic acid (C18:0) (r = 0.534, SCD-1(18) index had moderate to strong correlations with the VFA, whereas stearic acid (C18:0) /palmitic acid (C16:0) (r = 0.495, elongase of very long chain fatty acids (Elovl) 6 index exhibited a significant negative correlation. Conclusions: The serum palmitoleic acid (C16:1 n-7) level and some estimated activity indices significantly correlated with the VFA in the type 2 diabetic patients. SCD-1 indices and an Elovl6 index were reciprocally associated with the VFA. The SCD-1(16) index, which showed the strongest correlation with the VFA along with the negative association of the Elovl6 index, might be useful in estimating the VFA. 1 Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan 2 Department of Clinical Nutrittion, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan 3 Division of Energy Metabolism Research, Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan 4 International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan. 5 Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki, Japan 6 Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Chiyoda-ku, Tokyo, Japan *Corresponding author: Shigeru Yatoh, Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-0031, Japan, Tel: +81-29-853-3053; Fax: +81-29-853-3174; E-mail: yatou-endo@umin.ac.jp Citation: Yatoh, S., et al. Estimated Stearoyl-CoA-desaturase (SCD)-1 and Elongase of Very Long Chain Fatty Acids (Elovl) 6 Activities From Serum Fatty Acids Are Reciprocally Associated with Visceral Fat Area in Type 2 Diabetic Patients. (2018) J diab Obes 5(1): 4147. Received Date: June 20, 2018 Accepted Date: July 11, 2018 Published Date: July 16, 2018 Introduction Abdominal visceral fat accumulation can cause insulin resistance in persons with type 2 diabetes. We hypothesized that desaturase or elongase activities could reflect the visceral fat area (VFA), thus minimizing the need for measurements of the VFA by computed tomography. Because direct measurement of tissue desaturase activities is difficult in humans, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies. Estimated D9(or stearoyl-CoA-desaturase (SCD)-1), D6and D5-desaturase activities have been associated with the percentage of body fat[1], metabolic syndrome[2], myocardial infarction[3] and improvements in insulin sensitivity after lifestyle interventions[4]. Research Article DOI: 10.15436/2376-0494.18.1911 Vol 5:1 pp 41/47 Copyright: © 2018 Yatoh, S. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License. Citation: Yatoh, S., et al. Estimated Stearoyl-CoA-desaturase (SCD)-1 and Elongase of Very Long Chain Fatty Acids (Elovl) 6 Activities From Serum Fatty Acids Are Reciprocally Associated with Visceral Fat Area in Type 2 Diabetic Patients. (2018) J diab Obes 5(1): 4147. www.ommegaonline.org Vol 5:1 pp 42/47 We have investigated roles of elongases and desaturases with regard to physiology and pathology in mice .We reported[5] that loss of elongase of very long chain fatty acids family member 6 (Elovl6) function reduced stearic acid (C18:0) and oleic acid (C18:1n-9) levels and increased palmitic acid (C16:0) and palmitoleic acid (C16:1n-7) levels and that mice with targeted disruption of Elovl6 were protected against development of hepatic insulin resistance when fed a high-fat/high-sucrose diet despite hepatosteatosis and obesity similar to the wild-type mice. This result suggested that hepatic fatty acid composition, particularly C16:0 to C18:0 conversion, was crucial for insulin sensitivity rather than lipid accumulation. Elovl6 belongs to an elongase family of microsomal enzymes and involves the elongation of saturated and monounsaturated fatty acids with 12, 14, 16 carbons, mainly converting C16 to C18. Elovl6 is also a gene target of sterol regulatory element-binding protein (SREBP)1, a crucial transcription factor for fatty acid synthesis, playing a role in both lipid and glucose metabolism[6,7]. Clinically, genetic variations in the Elovl6 gene have a significant association with insulin sensitivity in population-based studies[8,9]. Furthermore, we revealed that Elovl6 knockout mice are markedly resistant to atherosclerosis and nonalcoholic steatohepatitis (NASH) presumably due to the altered fatty acid composition in the macrophages and liver, respectively[10,11]. Conversely, over expression of the Elovl6 gene promoted NASH in mouse models[12]. We also recognized the alteration of fatty acid composition regulated by Elovl6 , involved various pathophysiologies in other tissues such as lung fibrosis, vascular smooth muscle cell proliferation following wire injury, and chondrocyte growth and differentiation[13-15]. Through these findings, we hypothesized fatty acid composition should associate with the pathology of obesity-related metabolic diseases in human. In type 2 diabetic patients, visceral fat accumulation is known to be associated with and presumably induces insulin resistance. However, the association of visceral fat accumulation with particular desaturase or elongase activities, has not been fully revealed. Therefore, we investigated the association between the VFA and various surrogate indices of desaturases and elongases which were calculated from serum concentrations of fatty acids in type 2 diabetic patients. Materials and Methods Study participants This retrospective study utilized data collected from inpatients who had been hospitalized in the Department of Endocrinology and Metabolism in University of Tsukuba Hospital between April 2009 and March 2012. Inclusion criteria were having type 2 diabetes, age > 20 years, and having had an abdominal computed tomography (CT) scan and measurement of serum fatty acids during hospitalization. Exclusion criteria were liver cirrhosis, diabetic ketoacidosis, hyperosmolar hyperglycemic state, administration of eicosapentaenoic acid (C20:5 n-3) or adrenocortical hormones, emaciation (body mass index < 18.5 kg/m2), and malnutrition. We identified 32 patients who met the inclusion criteria and exclusion criteria (19 mean, 13 women). The following information and data were collected from their medical records: age, sex, body mass index, medical history, medications, glycated hemoglobin(HbA1c), and fasting concentrations of glucose, insulin, C-peptide, free fatty acids, triglycerides and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol. Existence or nonexistence of fatty liver was confirmed through the examination of reports of abdominal ultrasonography. Table 1 shows the characteristics of the study patients. Table 1: Characteristics of study participants