Dual Metabolic Defects Are Required to Produce Hypertriglyceridemia in Obese Subjects

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 31; no. 9; pp. 2144 - 2150
• Main Authors: Taskinen, Marja-Riitta, Adiels, Martin, Westerbacka, Jukka, Söderlund, Sanni, Kahri, Juhani, Lundbom, Nina, Lundbom, Jesper, Hakkarainen, Antti, Olofsson, Sven-Olof, Orho-Melander, Marju, Borén, Jan
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.09.2011; Lippincott Williams & Wilkins
• Subjects: Abdominal Fat - metabolism; Adult; apoB-100; Apolipoprotein C-III - physiology; apolipoproteins; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiac and Cardiovascular Systems; Cardiology and Cardiovascular Disease; Cardiology. Vascular system; Cardiovascular system; Clinical Medicine; diabetes; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fatty Acids, Nonesterified - blood; Humans; Hypertriglyceridemia - etiology; Intra-Abdominal Fat - metabolism; Investigative techniques, diagnostic techniques (general aspects); Kardiologi; Kardiologi och kardiovaskulära sjukdomar; Klinisk medicin; lipoproteins; Lipoproteins, VLDL - metabolism; Liver - metabolism; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; metabolic syndrome; metabolism; Middle Aged; obesity; Obesity - metabolism; triglycerides; Triglycerides - metabolism; Ultrasonic investigative techniques; Human; Obesity; apolipoproteins; Nutrition disorder; Metabolic diseases; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Apolipoprotein; Lipoprotein; Metabolism; Triglyceride; Enzymopathy; Vascular disease; Hypertriglyceridemia; Atherosclerosis; Dyslipemia; Nutritional status; lipoproteins
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.111.224808

OBJECTIVE—Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects. METHODS AND RESULTS—Stable isotope tracers were used to elucidate the pathophysiology of the dyslipidemia in hypertriglyceridemic (n=14) and normotriglyceridemic (n=14) obese men (with comparable body mass index and visceral fat volume) and in normotriglyceridemic nonobese men (n=10). Liver fat was determined using proton magnetic resonance spectroscopy, and subcutaneous abdominal and visceral fat were measured by magnetic resonance imaging. Serum triglycerides in obese subjects were increased by the combination of increased secretion and severely impaired clearance of triglyceride-rich very-low-density lipoprotein1 particles. Furthermore, increased liver and subcutaneous abdominal fat were linked to increased secretion of very-low-density lipoprotein 1 particles, whereas increased plasma levels of apolipoprotein C-III were associated with impaired clearance in obese hypertriglyceridemic subjects. CONCLUSION—Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects with similar levels of visceral adiposity. The results emphasize the clinical importance of assessing hypertriglyceridemic waist in obese subjects to identify subjects at high cardiometabolic risk.