Suppression of Hepatic Cholesteryl Ester Transfer Protein Expression in Obese Humans with the Development of Type 2 Diabetes Mellitus

MacLean, Paul S.; Vadlamudi, Satyaprasad; MacDonald, Kenneth G.; Pories, Walter J.; Barakat, Hisham A.

doi:10.1210/jc.2004-1325

Cited by 24 publications

(19 citation statements)

References 55 publications

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“…Our data showed that generally serum CETP concentrations were significantly lower in patients than in a healthy control group, although 5.7% of patients had elevated CETP concentrations. This finding is similar to other re- ports [19][20][21] but not to others [5,14,[22][23][24] in which CETP concentration was approximately the same in diabetic subjects and normal controls [5,14,22] or elevated in type 1 or type 2 diabetic patients [23,24] and diabetic cynomolgus monkeys [12] . The discrepancies could be due to differences in assay method, type of diabetes, genetic or ethnic background.…”

Section: Discussionsupporting

confidence: 90%

Serum Cholesteryl Ester Transfer Protein Concentrations Are Associated with Serum Levels of Total Cholesterol, Beta-Lipoprotein and Apoproteins in Patients with Type 2 Diabetes Mellitus

Inukai

Ito²,

Hara³

et al. 2007

Med Princ Pract

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Objective: To investigate the role of serum cholesterol ester transfer protein (CETP) and the metabolism of various lipids including apoproteins in patients with type 2 diabetes. Materials and Methods: The relationships between serum concentrations of CETP and various lipids and apoproteins were investigated in 193 patients with type 2 diabetes mellitus and 68 age-matched healthy subjects. Serum CETP concentrations were measured by an enzyme-linked immunosorbent assay. Results: Serum CETP values were lower in diabetic patients than in healthy controls (p < 0.01). Female diabetic patients had significantly higher CETP concentrations than male patients. Serum CETP concentrations exhibited a significant positive correlation with serum concentrations of cholesterol (TC) and β-lipoproteins in diabetic patients (r = 0.485, p = 0.013). Patients with relatively high serum concentrations of high-density lipoprotein cholesterol (HDL-C) tended to have much lower CETP concentrations than patients with lower HDL-C concentrations. Serum CETP concentrations showed significant positive correlations with those of apoproteins B (Apo B; r = 0.384, p = 0.024) and E (Apo E; r = 0.341, p = 0.035). Conclusion: The data indicate that serum CETP is closely involved in the metabolism of TC, β-lipoprotein, Apo B and Apo E in type 2 diabetic patients.

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Section: Discussionsupporting

confidence: 90%

Serum Cholesteryl Ester Transfer Protein Concentrations Are Associated with Serum Levels of Total Cholesterol, Beta-Lipoprotein and Apoproteins in Patients with Type 2 Diabetes Mellitus

Inukai

Ito²,

Hara³

et al. 2007

Med Princ Pract

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“…The effect of the diabetic state on plasma CETP concentration appeared to be attributable to an increased level in diabetic female subjects. The effect of obesity on plasma CETP mass may be absent in diabetes (31), and plasma CETP was unrelated to BMI in the currently studied diabetic patients. Therefore, the higher BMI in female compared with male diabetic subjects does not explain their higher plasma CETP concentration.…”

Section: Discussionmentioning

confidence: 72%

Plasma Cholesteryl Ester Transfer Is a Determinant of Intima-Media Thickness in Type 2 Diabetic and Nondiabetic Subjects

et al. 2005

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We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers, no insulin or lipid-lowering drug treatment) and 82 control subjects, IMT, plasma CET, CETP mass, and lipids were determined. HDL cholesterol was lower, whereas IMT, pulse pressure, plasma triglycerides, and plasma CET and CETP concentration were higher in diabetic patients versus control subjects. In diabetic patients, plasma CET was positively determined by triglycerides (P < 0.001), non-HDL cholesterol (P < 0.001), CETP (P ‫؍‬ 0.002), and the interaction between CETP and triglycerides (P ‫؍‬ 0.004). In control subjects, plasma CET was positively related to triglycerides (P < 0.001) and non-HDL cholesterol (P < 0.001). HDL cholesterol was inversely related to plasma CET in each group (P < 0.01 for both). IMT was positively associated with plasma CET in diabetic (P ‫؍‬ 0.05) and control (P < 0.05) subjects after adjustment for age, sex, and pulse pressure. No independent relationship with plasma CETP mass was found. Plasma CET is a positive determinant of IMT. Plasma CETP mass, in turn, is a determinant of CET with an increasing effect at higher triglycerides. These data, therefore, provide a rationale to evaluate the effects of CETP inhibitor treatment on plasma CET and on cardiovascular risk in diabetes-associated hypertriglyceridemia. Diabetes 54:3554 -3559, 2005 T he inverse relationship between HDL cholesterol and cardiovascular disease is well documented in nondiabetic and type 2 diabetic populations (1,2). Among other mechanisms, the cholesteryl ester transfer protein (CETP)-mediated process of plasma CET plays a key role in HDL metabolism. CETP transfers cholesteryl esters from HDL toward lipoproteins of lowerdensity classes in exchange for triglycerides (3-5). Hence, the plasma CET process is likely to contribute to low HDL cholesterol, as frequently observed in type 2 diabetes (5).Only few studies have addressed the effect of plasma CETP levels and the rate of plasma CET on cardiovascular risk in humans. A small study showed a positive correlation between the plasma CETP concentration and carotid artery intima-media thickness (IMT) (6). In addition, plasma CETP mass was shown to be a positive determinant of incident coronary artery disease but only in subjects with high triglycerides (7). The CET process itself could, however, also represent a beneficial pathway by enabling the transport of HDL-derived cholesteryl esters back to the liver via VLDL and LDL (3). The impact of the plasma CET process on atherosclerosis development remains, therefore, uncertain (8).CETP inhibitors represent a new class of drugs that effectively raise HDL cholesterol (9,10). While pharmacological inhibition of circulating CETP has been shown to retard atherosclerosis in animal experiments (11), the effect of this treatment on ca...

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“…Plasma glucose, triglycerides (TG), free fatty acids, and total cholesterol were assayed as previously described (28). Urinary nitrogen was estimated from measurements of urea and creatine in 24-h urine collections (25,27), and these samples were also used to estimate 24-h corticosterone release (25).…”

Section: Methodsmentioning

confidence: 99%

Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss

MacLean¹,

Higgins²,

Wyatt³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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118

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Brown IE, Hill JO. Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss. Am J Physiol Regul Integr Comp Physiol 297: R793-R802, 2009. First published July 8, 2009 doi:10.1152/ajpregu.00192.2009.-Weight loss is accompanied by several metabolic adaptations that work together to promote rapid, efficient regain. We employed a rodent model of regain to examine the effects of a regular bout of treadmill exercise on these adaptations. Obesity was induced in obesity-prone rats with 16 wk of high-fat feeding and limited physical activity. Obese rats were then weight reduced (ϳ14% of body wt) with a calorie-restricted, low-fat diet and maintained at that reduced weight for 8 wk by providing limited provisions of the diet with (EX) or without (SED) a daily bout of treadmill exercise (15 m/min, 30 min/day, 6 days/wk). Weight regain, energy balance, fuel utilization, adipocyte cellularity, and humoral signals of adiposity were monitored during eight subsequent weeks of ad libitum feeding while the rats maintained their respective regimens of physical activity. Regular exercise decreased the rate of regain early in relapse and lowered the defended body weight. During weight maintenance, regular exercise reduced the biological drive to eat so that it came closer to matching the suppressed level of energy expenditure. The diurnal extremes in fuel preference observed in weight-reduced rats were blunted, since exercise promoted the oxidation of fat during periods of feeding (dark cycle) and promoted the oxidation of carbohydrate (CHO) later in the day during periods of deprivation (light cycle) . At the end of relapse, exercise reestablished the homeostatic steady state between intake and expenditure to defend a lower body weight. Compared with SED rats, relapsed EX rats exhibited a reduced turnover of energy, a lower 24-h oxidation of CHO, fewer adipocytes in abdominal fat pads, and peripheral signals that overestimated their adiposity. These observations indicate that regimented exercise altered several metabolic adaptations to weight reduction in a manner that would coordinately attenuate the propensity to regain lost weight. fat oxidation; energy balance; indirect calorimetry; postobese; adipocyte cellularity WEIGHT REGAIN AFTER WEIGHT loss has been repeatedly shown in both obese animals (3, 4, 6, 9, 21-23, 25, 26, 30) and humans (14,18,32,42,43). A meta-analysis of a large number of U.S. weight loss studies summarized the propensity to regain after a wide variety of weight loss programs (1). Not only does lost weight tend to return, but the rate of return is highest immediately after the cessation of the structured weight loss program. Over 35% of the lost weight returns in the first year, and the majority is gained back within five years. Most people view their weight loss program as a transient change in their lifestyle and dietary habits or have difficulty in sustaining the changes that they have made to lose the weight (7, 11).The proposed reasons for the high rate of weight rega...

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Suppression of Hepatic Cholesteryl Ester Transfer Protein Expression in Obese Humans with the Development of Type 2 Diabetes Mellitus

Cited by 24 publications

References 55 publications

Serum Cholesteryl Ester Transfer Protein Concentrations Are Associated with Serum Levels of Total Cholesterol, Beta-Lipoprotein and Apoproteins in Patients with Type 2 Diabetes Mellitus

Serum Cholesteryl Ester Transfer Protein Concentrations Are Associated with Serum Levels of Total Cholesterol, Beta-Lipoprotein and Apoproteins in Patients with Type 2 Diabetes Mellitus

Plasma Cholesteryl Ester Transfer Is a Determinant of Intima-Media Thickness in Type 2 Diabetic and Nondiabetic Subjects

Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss

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