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 (nϭ14) and normotriglyceridemic (nϭ14) obese men (with comparable body mass index and visceral fat volume) and in normotriglyceridemic nonobese men (nϭ10). 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 lipoprotein 1 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. Key Words: apolipoproteins Ⅲ lipoproteins Ⅲ metabolism Ⅲ obesity T he rapid increase in obesity prevalence is one of the major health problems in Western societies and a growing problem in developing countries. 1 Obesity is commonly associated with several metabolic complications, including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, gout, and increased risk of cardiovascular disease. However, obesity is heterogeneous with respect to its adverse metabolic consequences and cardiovascular disease risk, and up to 20% to 30% of obese subjects seem to be metabolically normal. 2 See accompanying article on page 1946In "unhealthy" obesity, the adipose tissue storage capacity is exceeded, which results in ectopic lipid accumulation in several tissues, including liver, skeletal muscle, pancreas, and heart. 3 Ectopic fat deposition is reported to associate with a plethora of cardiometabolic risk factors. 1,4 In particular, several epidemiological studies indicate that nonalcoholic fatty liver disease (NAFLD), especially in its more severe forms, is linked to an increased risk of cardiovascular disease, independently of underlying cardiometabolic risk factors. [5][6][7] This suggests that NAFLD is not merely a marker of cardiovascular disease but may also be actively involved in its pathogenesis. NAFLD is the most common cause of chronic liver disease, with a prevalence of approximately 20% to 30% in the general population and 70% to 80% in patients with type 2 diabetes. 8 We have recently shown that the deposition of fat in the liver is a stronger de...

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