T he prevalence of obesity is steadily increasing so much, so that obesity has become a pandemic in developed and developing nations. 1 The increased risk of morbidity and mortality and more particularly of atherosclerotic cardiovascular disease associated with obesity and insulin-resistant states is of great public health concern.2,3 Each 5 kg/m 2 increase above a body mass index (BMI) of 25 kg/m 2 results in a 40% increase in cardiovascular mortality.3 Dyslipidemia is a prominent feature of obesity and insulin-resistant states. 4 The typical dyslipidemia associated with these conditions is mainly characterized by elevated plasma triglyceride concentration, low high-density lipoprotein-cholesterol (HDL-C) level, increased proportion of small and dense low-density lipoprotein (LDL), and postprandial hyperlipidemia.4,5 These abnormalities contribute to the high residual cardiovascular risk observed in obesity and insulin-resistant states, even if low LDL-C levels are achieved by statin treatment.6,7 The pathophysiology of this dyslipidemia is widely explained by the blood accumulation of triglyceride-rich lipoproteins (TRL) from the liver (apolipoprotein [apo]B-100-containing very low-density lipoprotein [VLDL]) and the intestine (apoB-48-containing chylomicrons). This accumulation has been attributed to the © 2014 American Heart Association, Inc. Objective-The dyslipidemia of obesity and other insulin-resistant states is characterized by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (apoB-100-containing very low-density lipoprotein) and intestinal (apoB-48-containing chylomicrons) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity and is associated with improvements in several metabolic abnormalities associated with obesity, including a reduction in plasma triglycerides. Here, we have investigated the effect of bariatric surgery on TRL metabolism. Approach and Results-Twenty-two nondiabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (n=12) or gastric bypass (n=10) were studied. Each subject underwent 1 lipoprotein turnover study 1 month before surgery followed by a second study, 6 months after surgery, using established stable isotope enrichment methodology, in constant fed state. TRL-apoB-100 concentration was significantly reduced after sleeve gastrectomy, explained by a decrease (P<0.05) in TRL-apoB-100 production rate and an increase (P<0.05) in TRL-apoB-100 fractional catabolic rate. TRLapoB-48 concentration was also significantly reduced after sleeve gastrectomy, explained by reduction in TRL-apoB-48 production rate (P<0.05). For gastric bypass, although TRL-apoB-100 concentration declined after surgery (P<0.01), without a significant decline in TRL-apoB-48, there was no significant change in either TRL-apoB-100 or TRL-apoB-48 production rate or fractional catabolic rate. The reduction in TRL-apoB-100 concentration was significantly associated with a reduction in plasma apoC-III in the pooled group of pati...
Objective-Overproduction of intestinally derived apoB-48-containing triglyceride-rich lipoproteins (TRLs) (chylomicrons) has recently been described in type 2 diabetes, as is known for hepatic TRL-apoB-100 (very-low-density lipoprotein) production. Furthermore, insulin acutely inhibits both intestinal and hepatic TRL production, whereas this acute inhibitory effect on very-low-density lipoprotein production is blunted in type 2 diabetes. It is not currently known whether this acute effect on chylomicron production is similarly blunted in humans with type 2 diabetes. Methods and Results-We investigated the effect of acute hyperinsulinemia on TRL metabolism in 18 type 2 diabetic men using stable isotope methodology. Each subject underwent 1 control (saline infusion [SAL]) lipoprotein turnover study followed by a second study, under 1 of the 3 following clamp conditions: (1) hyperinsulinemic-euglycemic, (2) hyperinsulinemic-hyperglycemic, or (3) hyperinsulinemic-euglycemic plus intralipid and heparin. TRL-apoB-48 and TRL-apoB-100 production and clearance rates were not different between SAL and clamp and between the different clamp conditions, except for significantly lower TRL-apoB-100 clearance and production rates in hyperinsulinemiceuglycemic plus intralipid and heparin clamp compared with SAL. Conclusion-This is the first demonstration in individuals with type 2 diabetes that chylomicron production is resistant to the normal acute suppressive effect of insulin. This phenomenon may contribute to the highly prevalent dyslipidemia of type 2 diabetes and potentially to atherosclerosis. Key Words: apolipoproteins Ⅲ atherosclerosis Ⅲ diabetes mellitus Ⅲ fatty acids Ⅲ lipoproteins T he increased risk of atherosclerotic cardiovascular disease associated with insulin-resistant states and type 2 diabetes is of great public health concern.1 The typical diabetic dyslipidemia is characterized by a number of abnormalities, including elevated plasma triglyceride (TG) levels, low high-density lipoprotein cholesterol, increased proportion of small and dense low-density lipoprotein, and postprandial hyperlipidemia.2 Dyslipidemia in insulin-resistant states contributes to the residual cardiovascular risk and atherosclerosis. [3][4][5] Diabetic dyslipidemia includes characteristic accumulation of triglyceride-rich lipoproteins (TRLs), which has been attributed to a combination of defective TRL removal and overproduction from liver (TRL-apoB-100 or very-low-density lipoprotein [VLDL]) 3 and from intestine (TRLapoB-48 or chylomicrons).6-8 TRL-apoB-48 and TRL-apoB-100 have been identified as proatherogenic in type 2 diabetes. 9The mechanisms leading to the overproduction of TRLs in the setting of type 2 diabetes and insulin resistance remain to be fully characterized, particularly for intestine. We have recently shown that acute elevation of plasma free fatty acids (FFA) stimulates not only hepatic but also intestinal TRL production in Syrian Golden hamsters 10 and in fed healthy humans, 11 demonstrating functional similarities bet...
BACKGROUND: Elevated apolipoprotein C-III (apoC-III) has been postulated to contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL) metabolism. Bariatric surgery is associated with improvements of several obesity-associated metabolic abnormalities, including a reduction in plasma triglycerides (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C).OBJECTIVES: We investigated the specific effect of bariatric surgery on apoC-III concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile parameters evolution.METHODS: A total of 132 obese subjects undergoing bariatric surgery, gastric bypass (n 5 61) or sleeve gastrectomy (n 5 71), were studied 1 month before surgery and 6 and 12 months after surgery.RESULTS: Plasma apoC-III, non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after surgery and strongly associated with reduction in plasma TG. This decrease was E-mail address: rvalero@mail.ap-hm.fr accompanied by a redistribution of apoC-III from TRL to HDL fractions. In multivariate analysis, plasma apoC-III was the strongest predictor of TG reduction after surgery, and the increase of HDL-C was positively associated with plasma adiponectin and negatively with body mass index.CONCLUSION: Marked reduction of apoC-III and changes in its distribution between TRL and HDL consistent with a better lipid profile are achieved in obese patients after bariatric surgery. These apoC-III beneficial modifications may have implications in dyslipidemia improvement and contribute to cardiovascular risk reduction after surgery.
In order to address the increasing prevalence of overweight and obesity in children, the French city of Narbonne recently began monitoring childhood obesity with a view to developing and implementing targeted actions to stabilize the prevalence of overweight. The main purpose of this study was to assess the risk factors for overweight in children. The study was conducted during the 2008-2009 academic year and was based on a sample of 1,476 preschool and primary school children from all public and private schools in Narbonne. The prevalence of overweight and obesity were 14.9% and 3.7%, respectively. The study found that watching television for more than 2 hours a day, short sleep duration (less than 10 hours per night), a low socioeconomic status and parental obesity are risk factors for overweight and obesity in children. The findings suggest that priority actions among poor populations and overweight mothers are required in order to stabilize the prevalence of overweight and obesity in children, including providing advice on healthy eating, fighting against sedentary lifestyles and promoting sleep.
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