Plasma Concentrations and Subcutaneous Adipose Tissue mRNA Expression of Clusterin in Obesity and Type 2 Diabetes Mellitus: the Effect of Short-Term Hyperinsulinemia, Very-Low-Calorie Diet and Bariatric Surgery

Kloučková, Jana; Lacinová, Z; Kaválková, Petra; Trachta, Pavel; Kasalický, M; Haluzíková, D; Mráz, Miloš; Haluzı́k, Martin

doi:10.33549/physiolres.933121

Cited by 12 publications

(14 citation statements)

References 28 publications

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“…In support of our results, previous studies by Won et al in 204 Korean adults also demonstrated higher clusterin levels in overweight/obese subjects than in lean subjects as well as a positive relationship between serum clusterin levels and BMI . Serum clusterin levels were significantly reduced after weight reduction in obese subjects who underwent very‐low‐calorie diet treatment . All these results suggest that obesity is a factor that influences clusterin levels.…”

Section: Discussionsupporting

confidence: 91%

High serum clusterin levels are associated with premature coronary artery disease in a Chinese population

Zhu

Liu

Zhai

et al. 2019

Diabetes Metabolism Res

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Background: Clusterin plays an important role in the cardiovascular system, and serum levels of clusterin are higher in coronary artery disease patients. Here, we measured serum clusterin levels in premature coronary artery disease (PCAD) patients and explored the association of these levels with PCAD risk. Methods:Serum samples and general clinical information were obtained from 672 subjects including 364 PCAD subjects, 126 non-PCAD subjects, and 182 controls.Results: Serum clusterin levels were higher in PCAD patients than in controls, particularly in males with body mass index (BMI) < 25 kg/m 2 (P < 0.0001). Compared with the lowest tertile of clusterin, the odds ratio of PCAD in the highest tertile was higher in both a univariate and three adjustment models, and it was 3.146-fold higher in Model 3. This association was especially significant in subgroups with BMI < 25 kg/m 2 , total cholesterol < 5.7 mmol/L, high-density lipoprotein cholesterol ≥ 1.0 mmol/L, Urea < 7.14 mmol/L, and estimated glomerular filtration rate < 90 mL/min/1.73 m 2 . Serum clusterin may be a potential diagnostic biomarker for PCAD (sensitivity 60.7%, specificity 51.6%, area under the curve 0.595 [95% CI, 0.544-0.647], P < 0.0001), and a combination of clusterin with clinical variables in Model 3 resulted in improved diagnostic accuracy (sensitivity 86.3%, specificity 64.2%, area under the curve 0.829 [95% CI, 0.782-0.877], P < 0.0001).Conclusions: Serum clusterin levels were increased in PCAD patients, especially for males with BMI < 25 kg/m 2 . Higher clusterin levels were independently associated with the presence of PCAD, particularly in subjects with normal BMI, lower total cholesterol, urea, estimated glomerular filtration rate, and higher high-density lipoprotein cholesterol. Clusterin might be a potential diagnostic biomarker for PCAD patients, especially in combination with clinical variables. KEYWORDS body mass index (BMI), clusterin, nonpremature coronary artery disease (NPCAD), premature coronary artery disease (PCAD), risk factors

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Section: Discussionsupporting

confidence: 91%

High serum clusterin levels are associated with premature coronary artery disease in a Chinese population

Zhu

Liu

Zhai

et al. 2019

Diabetes Metabolism Res

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“…Increased CLU levels are associated with T2DM, metabolic syndrome and cardiovascular diseases [44,45]. Kujiraoka et al [46] reported higher serum CLU levels in diabetes patients than in patients with myocardial infarction, chronic coronary artery disease, or diabetes combined with chronic coronary artery disease.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide-1 levels and dipeptidyl peptidase-4 activity in type 2 diabetes

Şenyiğit

Tabak

Orhanoğlu

et al. 2017

CIM

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“…In the only study of AT CLU, a 2-week very-low-calorie diet reduced plasma clusterin levels, and whole fat clusterin mRNA decreased after sleeve gastrectomy (43). In obese subjects, plasma clusterin levels were elevated and positively associated with BMI, inflammation (hs-CRP and retinol-binding protein-4) (16), and IR (14).…”

Section: Discussionmentioning

confidence: 99%

Clusterin Impairs Hepatic Insulin Sensitivity and Adipocyte Clusterin Associates With Cardiometabolic Risk

et al. 2019

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Components of the adipose tissue (AT) extracellular matrix (ECM) are recently discovered contributors to obesity-related cardiometabolic disease. We identified increased adipocyte expression of ECM-related clusterin (apolipoprotein J) in obese versus lean women by microarray. Our objective was to determine 1) whether subcutaneous AT adipocyte (SAd) clusterin and serum clusterin are associated with insulin resistance (IR) and known markers of cardiometabolic risk and 2) how clusterin may contribute to increased risk. RESEARCH DESIGN AND METHODS We validated increased clusterin expression in adipocytes from a separate group of 18 lean and 54 obese individuals. The relationship of clusterin gene expression and plasma clusterin with IR, cardiovascular biomarkers, and risk of cardiovascular disease (CVD) was then determined. Further investigations in human cultured cells and in aged LDLR 2/2 mice prone to development of obesityassociated complications were performed. RESULTS SAd clusterin correlated with IR, multiple CVD biomarkers, and CVD risk, independent of traditional risk factors. Circulating human clusterin exhibited similar associations. In human adipocytes, palmitate enhanced clusterin secretion, and in human hepatocytes, clusterin attenuated insulin signaling and APOA1 expression and stimulated hepatic gluconeogenesis. LRP2 (megalin), a clusterin receptor, highly expressed in liver, mediated these effects, which were inhibited by LRP2 siRNA. In response to Western diet feeding, an increase in adipocyte clusterin expression was associated with a progressive increase in liver fat, steatohepatitis, and fibrosis in aged LDLR 2/2 mice. CONCLUSIONS Adipocyte-derived clusterin is a novel ECM-related protein linking cardiometabolic disease and obesity through its actions in the liver. Obesity is associated with a heightened cardiovascular disease (CVD) risk profile that encompasses insulin resistance (IR), type 2 diabetes, hypertension, dyslipidemia, and hepatic steatosisdall components of the well-described metabolic syndrome (1,2). These factors act synergistically to accelerate morbidity and mortality in obesity (3). IR stems from adipocyte lipolysis and lipid deposition into insulin target tissues, as well

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Plasma Concentrations and Subcutaneous Adipose Tissue mRNA Expression of Clusterin in Obesity and Type 2 Diabetes Mellitus: the Effect of Short-Term Hyperinsulinemia, Very-Low-Calorie Diet and Bariatric Surgery

Cited by 12 publications

References 28 publications

High serum clusterin levels are associated with premature coronary artery disease in a Chinese population

High serum clusterin levels are associated with premature coronary artery disease in a Chinese population

Glucagon-like peptide-1 levels and dipeptidyl peptidase-4 activity in type 2 diabetes

Clusterin Impairs Hepatic Insulin Sensitivity and Adipocyte Clusterin Associates With Cardiometabolic Risk

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