Houshang Monajemi

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (14)47.57 Total impact

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    ABSTRACT: Familial partial lipodystrophy type 3 (FPLD) is an autosomal dominant disease characterized by aberrant adipose distribution and metabolic disturbances, including insulin resistance and dyslipidemia.
    11/2015; 10(3):161-161. DOI:10.1007/s12467-012-0121-0
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    ABSTRACT: Obesity and its metabolic complications are important risk factors for cardiovascular disease. Obesity is associated with adipose tissue (AT) inflammation, initiated by adipocyte hypertrophy and ultimately resulting in low-grade systemic inflammation. Complex intercellular communication between adipocytes and AT-resident immune cells underlie AT inflammation.
    11/2015; 10(3):150-151. DOI:10.1007/s12467-012-0107-y
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    ABSTRACT: We investigated the postprandial changes in plasma levels of adipocytokines in overweight patients with metabolic syndrome after an oral fat load. After an oral fat load and during a prolonged fast, blood was drawn at 0, 2, 3, 4 and 8 h for measurement of adiponectin, adipsin, cathepsin S, chemerin, hepatic growth factor, interferon-γ-inducible protein-10, leptin, macrophage chemoattractant protein-1, macrophage migration inhibitory factor, nerve growth factor, retinol binding protein-4, resistin, serum amyloid A1, tissue inhibitor of metalloproteinase-1 and thrombopoietin using a microbead-based Luminex assay. Area under the curves (AUC) were calculated and compared. Plasma adiponectin levels were higher after an oral fat load compared to fasting at t = 2 h (950 ± 513 vs. -1,881 ± 713 ng/ml) while the plasma levels for adipsin (-9 ± 5 vs. 16 ± 5 ng/ml), chemerin (-122 ± 35 vs. 13 ± 21 ng/ml), SAA-1 (-391 ± 213 vs. 522 ± 173 ng/ml) and TPO (-335 ± 144 vs. 622 ± 216 ng/ml) were lower after an oral fat load compared to fasting. The baseline corrected AUC for IP-10 was higher after fat load compared to fasting (median -116 pg h/ml; IQR -270 to 10 vs. -21 pg h/ml; IQR -136 to 418 (p = 0.047). In conclusion, in overweight male subjects with the metabolic syndrome, an oral fat load is accompanied with a modest anti-inflammatory response of adipose tissue-derived adipocytokines.
    Lipids 01/2014; 49(3). DOI:10.1007/s11745-014-3877-8 · 1.85 Impact Factor
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    ABSTRACT: We investigated whether plasma ferritin levels through the pro-inflammatory effects of free iron are associated with adipose tissue dysfunction in a relevant population of patients with manifest vascular disease who would potentially benefit the most from further aetiological insights. In a cohort of 355 patients with vascular diseases, the association between plasma ferritin and adiponectin levels was quantified using linear regression analysis. Interleukin-6 and adiponectin levels were measured in medium from pre-adipocytes and adipocytes after incubation with increasing concentrations of Fe(III)-citrate and after co-incubation with iron chelators or radical scavengers. Increasing ferritin plasma concentrations were not related to plasma adiponectin levels in patients without (β -0·13; 95% CI -0·30 to 0·04) or with the metabolic syndrome (β -0·04; 95% CI -0·17 to 0·10). Similar results were found in patients who developed a new cardiovascular event in the follow-up period. In vitro, incubation with increasing concentrations of Fe(III)-citrate-induced inflammation in pre-adipocyte cultures as witnessed by increased IL-6 secretion at 30 μm Fe(III)-citrate vs. control (500 ± 98 pg/mL vs. 194 ± 31 pg/mL, P = 0·03). Co-incubation of pre-adipocytes with iron chelators or radical scavengers prevented this inflammatory response. Incubation of adipocytes with 30 μm Fe(III)-citrate did not influence adiponectin secretion compared with control. In patients with vascular disease, there is no association between plasma ferritin and adiponectin levels. In vitro, free iron induces an inflammatory response in pre-adipocytes, but not in adipocytes. This response was blocked by co-incubation with iron chelators or radical scavengers. Adiponectin secretion by adipocytes was not influenced by free iron.
    European Journal of Clinical Investigation 12/2013; 43(12):1240-1249. DOI:10.1111/eci.12165 · 2.73 Impact Factor
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    ABSTRACT: Increased production of chemokines by adipose tissue and defective adipose tissue oxygenation as a result of obesity may induce leucocyte infiltration and subsequent systemic inflammation. 1-To determine the relation between the amount of visceral and subcutaneous adipose tissue and the chemokine interferon-γ-inducible protein 10 (IP-10) and angiogenic factor hepatocyte growth factor (HGF). 2-To determine the relation between the metabolic syndrome and IP-10 as well as HGF. Patients originated from the Secondary Manifestations of ARTerial disease (SMART) cohort. In this study, a cohort of 1251 patients with manifest vascular disease was included. Subcutaneous and visceral adipose tissue thickness (SAT and VAT respectively) were measured ultrasonographically. IP-10 and HGF concentrations were measured with Luminex multiplex immuno assay in addition to fasting metabolic parameters. Linear regression analyses with adjustments for age, gender, smoking, estimated glomerular filtration rate, type 2 diabetes mellitus and medication use were applied to quantify the relations between adiposity or metabolic syndrome and IP-10 and HGF concentrations. VAT was significantly associated with (log)IP-10 and (log)HGF, reflected by significant higher β-values in VAT quartile 4 compared with VAT quartile 1 (reference): β0.155 (95%CI:0.073–0.237) for IP-10 and β0.147 (95%CI:0.076–0.218) for HGF. Per standard deviation increase in VAT, (log)IP-10 levels increased with 0.057 pg/mL (95%CI:0.027–0.087) and (log)HGF increased with 0.051 pg/mL (95%CI:0.025–0.077). Effect estimates were not affected by including body mass index(BMI) in the model. In contrast, SAT was not associated with IP-10 and HGF. Furthermore, the presence of the metabolic syndrome was associated with IP-10 and HGF. Visceral adipose tissue but not subcutaneous adipose tissue is significantly associated with circulating levels of IP-10 and HGF, irrespective of BMI.
    European Journal of Clinical Investigation 02/2013; 43(4). DOI:10.1111/eci.12054 · 2.73 Impact Factor
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    ABSTRACT: BACKGROUND: Plasma triglyceride (TG) levels are known to confer an increased risk of vascular disease in healthy populations, but data in high-risk patients are scarce. In this study we evaluated the risk on recurrent vascular events conferred by increased plasma TG levels in patients with various clinical manifestations of vascular disease. METHODS: Prospective cohort study of 5731 patients with clinically manifest vascular disease. RESULTS: First new vascular events (myocardial infarction, ischemic stroke, vascular death) occurred in 782 subjects during a median follow-up of 4.9years (interquartile range 2.5-8.1years). Patients in the highest plasma TG quintile (>2.24mmol/L) had a higher risk for recurrent vascular events (HR 1.45; 95%CI 1.13-1.86) compared with the lowest plasma TG quintile (<0.97mmol/L) after adjustments for age, gender, body mass index, smoking, lipid-lowering medication and low-density lipoprotein-cholesterol. The increased risk associated with increasing plasma TG levels was irrespective of the presence of type 2 diabetes (T2DM), but only present in patients without the metabolic syndrome. Furthermore, the increased risk was particularly present in patients with coronary artery disease (CAD) (HR 1.45; 95%CI 1.02-2.08) and was not modified by other lipid levels (p-value for interaction >0.05). Plasma TG still contributed to vascular risk when other lipid levels were at target level. CONCLUSIONS: Higher plasma TG levels are associated with increased risk for recurrent vascular events, in particular in CAD patients. This increased risk is independent of the presence of T2DM and the use of lipid-lowering medication and is not modified by other lipid levels.
    International journal of cardiology 01/2012; 167(2). DOI:10.1016/j.ijcard.2012.01.008 · 4.04 Impact Factor
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    ABSTRACT: Adipose tissue dysfunction is associated with inflammation, type 2 diabetes mellitus and vascular diseases. Visceral adipose tissue (VAT)-derived adipokines, which are released in the portal circulation may influence liver metabolism. (1) To estimate the contribution of VAT and subcutaneous adipose tissue (SAT) on adipokine levels by measuring differences in adipokine concentrations between the portal draining inferior mesenteric vein and the subclavian vein. (2) To determine the relation of both VAT and SAT quantity and composition to mesenteric and systemic concentrations of adipokines. Cross-sectional cohort study. A total of 32 patients undergoing abdominal aortic surgery. A panel of 18 adipokines was measured in perioperatively obtained blood samples from the subclavian vein and the inferior mesenteric vein. Adipocyte size, macrophage infiltration and capillary density were measured in subcutaneous and mesenteric adipose tissue biopsies; SAT and VAT areas were measured on computed tomography images. Serum interferon-γ-inducible protein 10 (IP-10) and hepatocyte growth factor (HGF) concentrations were significantly higher in the inferior mesenteric vein vs the subclavian vein. SAT area (β -18; 95% confidence interval (CI) -35 to -2), subcutaneous adipocyte size (β -488; 95% CI -938 to -38) and SAT macrophages quantity (β -1439; 95% CI -2387 to -491) were negatively associated with adiponectin levels in the systemic circulation. SAT area was related to systemic concentrations of leptin. Mesenteric adiponectin concentrations were related to VAT area (β -20; 95% CI -35 to -5) and visceral adipocyte size (β -1076; 95% CI -1624 to -527). VAT area, adipocyte size and capillary density were related to systemic adiponectin concentrations. SAT and VAT quantities as well as morphologic characteristics of both adipose tissue depots are related to systemic and mesenteric adipokine concentrations. There were no differences in adipokine concentrations between the mesenteric and subclavian vein, except for higher IP-10 and HGF concentrations in the inferior mesenteric vein, indicating a possible contribution of VAT to IP-10 and HGF levels.
    International journal of obesity (2005) 11/2011; 36(8):1078-85. DOI:10.1038/ijo.2011.214 · 5.00 Impact Factor
  • Remco Franssen · Houshang Monajemi · Erik S.G. Stroes · John J.P. Kastelein ·
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    ABSTRACT: Dyslipidemia associated with obesity and the metabolic syndrome is one of the central features contributing to the increased CV risk in these patients. In view of the pandemic of the metabolic syndrome, it is imperative to fully understand the mechanisms leading to the metabolic lipid phenotype before embarking upon optimal treatment strategies. The traditional concept that insulin resistance causes increased FFA flux via increased TG hydrolysis in adipose tissue is still of a central theme in the general hypothesis. The combination of increased hepatic VLDL secretion with impaired LPL-mediated TG clearance explains the hypertriglyceridemia phenotype of the metabolic syndrome. Hence, central IR may be an important factor contributing to peripheral hypertriglyceridemia. Recently recognized regulatory systems include the profound impact of the hypothalamus on TG secretion and glucose control. In addition, dysfunctional (or inflamed) intra abdominal adipose tissue has emerged as a potent regulator of dyslipidemia and IR. It will be a challenge to design novel treatment modalities that target “dysfunctional” fat or central IR to attempt to prevent the epidemic of CV disease secondary to the metabolic syndrome.
    The Medical clinics of North America 09/2011; 95(5):893-902. DOI:10.1016/j.mcna.2011.06.003 · 2.61 Impact Factor
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    ABSTRACT: Elevated plasma triglyceride levels, as often seen in obese subjects, are independently associated with an increased risk of cardiovascular diseases. By secreting adipokines (such as adiponectin and leptin) and other proteins (such as lipoprotein lipase and cholesteryl ester transferase protein), adipose tissue affects triglyceride metabolism. In obesity, adipocyte hypertrophy leads to many changes in adipocyte function and production of anti- and pro-inflammatory cytokines. Furthermore, free fatty acids are released into the circulation contributing to insulin resistance. Adipose tissue dysfunction will eventually lead to abnormalities in lipid metabolism, such as hypertriglyceridemia (due to increased hepatic very-low-density lipoprotein production and decreased triglyceride hydrolysis), small dense low-density lipoprotein particles, remnant lipoproteins and low high-density lipoprotein cholesterol levels, all associated with a higher risk for the development of cardiovascular diseases. The clinical implications of elevated plasma triglycerides are still a matter of debate. Understanding the pathophysiology of adipose tissue dysfunction in obesity, which is becoming a pandemic condition, is essential for designing appropriate therapeutic interventions. Lifestyle changes are important to improve adipose tissue function in obese patients. Pharmacological interventions to improve adipose tissue function need further evaluation. Although statins are not very potent in reducing plasma triglycerides, they remain the mainstay of therapy for cardiovascular risk reduction in high-risk patients.
    Obesity Reviews 07/2011; 12(10):829-40. DOI:10.1111/j.1467-789X.2011.00900.x · 8.00 Impact Factor
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    ABSTRACT: Familial partial lipodystrophy (FPLD) is a rare metabolic disorder with clinical features that may not be readily recognised. As FPLD patients require a specific therapeutic approach, early identification is warranted. In the present study we aimed to identify cases of FPLD among non-obese patients with type 2 diabetes mellitus and marked insulin resistance. We searched the databases of three diabetic outpatient clinics for patients with marked insulin resistance, arbitrarily defined as the use of ≥100 U insulin/day, and BMI ≤ 27 kg/m(2). In all patients, metabolic variables and anthropomorphic measurements were evaluated and DNA was sequenced for mutations in the genes encoding lamin A/C (LMNA), peroxisome proliferator-activated receptor γ (PPARγ) and cell death-inducing DFFA-like effector c (CIDEC). Out of 5,221 diabetic individuals, 24 patients fulfilled all criteria. Twelve patients were willing to participate, of whom five showed clinical features of lipodystrophy. In three of these patients the clinical diagnosis of FPLD was confirmed by the presence of mutations in LMNA or PPARG; one patient harboured a novel heterozygous mutation (Y151C) in PPARG. The Y151C mutant displayed impaired DNA-binding capacity and hence reduced transcriptional activity compared with wild-type PPARγ. Dominant-negative activity was absent. The combination of BMI ≤ 27 kg/m(2) and the use of >100 U insulin/day increases the chance of identifying lipodystrophy. Thus careful assessment of clinical features of FPLD should be considered in these patients, allowing earlier therapeutic interventions.
    Diabetologia 07/2011; 54(7):1639-44. DOI:10.1007/s00125-011-2142-4 · 6.67 Impact Factor
  • Diederik F van Wijk · E.S.G. Stroes · Houshang Monajemi ·
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    ABSTRACT: The inverse correlation between HDL-C and atherosclerotic vascular disease is well established and lately research has focused on HDL as a potential target in the treatment of vascular disease. Traditionally, reverse cholesterol transport is considered to be the most important mechanism by which HDL protects against atherosclerosis. However, recent findings indicate that the role of HDL as an antiatherogenic particle is much more complex and research has focused on additional protective mechanisms, such as anti-inflammatory and antioxidative characteristics. However, these additional properties are still a matter of debate and currently no standardized, reproducible, high-throughput assays that can quantify those characteristics of HDL are available. Here we discuss the current knowledge on reverse cholesterol transport and the enzymes involved in HDL synthesis and remodeling. The interactions of the HDL particle with other cells that might play a crucial role in the additional protective mechanisms of HDL are also highlighted.
    Clinical Lipidology 02/2009; 4(1). DOI:10.2217/17584299.4.1.17 · 0.87 Impact Factor
  • Remco Franssen · Houshang Monajemi · Erik S G Stroes · John J P Kastelein ·
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    ABSTRACT: The alarming and still increasing prevalence of obesity and associated cardiovascular risk raises much concern. The increase in cardiovascular risk depends to a significant extent on the changes in lipid profiles as observed in obesity. These changes are decreased high-density lipoprotein cholesterol and increased triglyceride levels. Much effort has already been expended into the elucidation of the mechanisms behind these obesity-associated lipid changes. Insulin resistance certainly plays a central role and, in addition, both hormonal and neurologic pathways have recently been found to play an important role. This article focuses on the mechanisms involved in the development of the proatherogenic lipid changes associated with obesity.
    Endocrinology & Metabolism Clinics of North America 10/2008; 37(3):623-33, viii. DOI:10.1016/j.ecl.2008.06.003 · 3.40 Impact Factor
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    Houshang Monajemi · Erik Stroes · Robert A Hegele · Eric Fliers ·
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    ABSTRACT: Lipodystrophies represent a heterogeneous group of diseases characterized by an abnormal subcutaneous fat distribution, the extent of which can vary from localized, to partial, to generalized lipoatrophy. Whereas partial and generalized lipodystrophies are each associated with metabolic abnormalities, the localized form is not. These metabolic changes include insulin resistance with type 2 diabetes, acanthosis nigricans, dyslipidaemia predominantly consisting of hypertriglyceridaemia (associated with the onset of pancreatitis) and depressed HDL cholesterol, liver steatosis and hypertension. Affected women are often hirsute and this can be associated with the presence of polycystic ovarian syndrome (PCOS). Most of these clinical features are present to some extent in patients with the common metabolic syndrome. As the prevalence of metabolic syndrome far outweighs that of lipodystrophy, the diagnosis of this rare disorder may often be overlooked with the affected patient diagnosed as merely being 'yet' another case of metabolic syndrome. In this article, we draw attention to the importance of recognizing patients with lipodystrophy who present with metabolic abnormalities, as both the diagnostic as well as the therapeutic approach of these patients differ profoundly from patients with the metabolic syndrome.
    Clinical Endocrinology 11/2007; 67(4):479-84. DOI:10.1111/j.1365-2265.2007.02906.x · 3.46 Impact Factor
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    ABSTRACT: Familial partial lipodystrophy (FPLD) results from coding sequence mutations either in LMNA, encoding nuclear lamin A/C, or in PPARG, encoding peroxisome proliferator-activated receptor-gamma (PPARgamma). The LMNA form is called FPLD2 (MIM 151660) and the PPARG form is called FPLD3 (MIM 604367). Our objective was to investigate whether the clinical phenotype of this proband is due to mutation(s) in PPARgamma. This is a case report. Patient and Setting: A 31-yr-old female with the clinical phenotype of FPLD3, i.e. lipodystrophy and early childhood diabetes with extreme insulin resistance and hypertriglyceridemia leading to recurrent pancreatitis, was assessed at an academic medical center. The proband was heterozygous for a novel C-->T mutation in the PPARG gene that led to the substitution of arginine 194 in PPARgamma2 isoform, a conserved residue located in the zinc finger structure involved in DNA binding, by tryptophan (R194W). The mutation was absent from the genomes of 100 healthy Caucasians. In vitro analysis of the mutated protein showed that R194W (and R166W in PPARgamma1 isoform) could not bind to DNA and had no transcriptional activity. Furthermore, R194W had no dominant-negative activity. The R194W mutation in PPARG disrupts its DNA binding activity and through haploinsufficiency leads to clinical manifestation of FPLD3 and the associated metabolic disturbances.
    Journal of Clinical Endocrinology &amp Metabolism 06/2007; 92(5):1606-12. DOI:10.1210/jc.2006-1807 · 6.21 Impact Factor

Publication Stats

173 Citations
47.57 Total Impact Points


  • 2011-2013
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Utrecht, Netherlands
  • 2007-2011
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Vascular Medicine
      Amsterdam, North Holland, Netherlands