PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation.

Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation, and mutations that interfere with its function cause lipodystrophy. PPARγ is a highly modular protein, and structural studies indicate that PPARγ domains engage in several intra- and inter-molecular interactions. How these interactions modulate PPARγ's ability to activate target genes in a cellular context is currently poorly understood.

Smartphone Application-Assisted Home Blood Pressure Monitoring Compared With Office and Ambulatory Blood Pressure Monitoring in Patients With Hypertension: the AMUSE-BP Study.

Background: The development of automated, smartphone application (app)-assisted home blood pressure monitoring (HBPM) allows for standardized measurement of blood pressure (BP) at home. The aim of this study was to evaluate the (diagnostic) agreement between app-assisted HBPM, automated office BP (OBP), and the reference standard 24-hour ambulatory BP monitoring (ABPM).

Methods: In this open randomized 5-way cross-over study, patients diagnosed with hypertension were randomized to one of 10 clusters, each containing 5 BP measurement methods (ABPM, HBPM, attended OBP, unattended OBP, and unattended 30-minute BP) in different order.

Anti-Xa Levels in Morbidly Obese Patients Using Apixaban or Rivaroxaban, Before and After Bariatric Surgery.

Background: Despite limited evidence about the efficacy and safety of anticoagulation in patients post bariatric surgery, both vitamin K antagonists (VKA) and direct-acting oral anticoagulants (DOACs) are commonly prescribed.

Aim: To evaluate plasma anti-Xa levels of DOACs in morbidly obese (MO) patients before and after a Roux-en-Y gastric bypass (RYGB) procedure.

Patients And Methods: Retrospective, cross-sectional, and longitudinal study of anti-Xa activity of apixaban or rivaroxaban in MO patients (N = 41).

Assessment of Imaging Modalities Against Liver Biopsy in Nonalcoholic Fatty Liver Disease: The Amsterdam NAFLD-NASH Cohort.

Background: Noninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD.

Purpose: To examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores.

Arterial Wall Inflammation and Increased Hematopoietic Activity in Patients With Primary Aldosteronism.

Context: Primary aldosteronism (PA) confers an increased risk of cardiovascular disease (CVD), independent of blood pressure. Animal models have shown that aldosterone accelerates atherosclerosis through proinflammatory changes in innate immune cells; human data are scarce.

Objective: The objective of this article is to explore whether patients with PA have increased arterial wall inflammation, systemic inflammation, and reprogramming of monocytes.

Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia-reperfusion injury: A prospective case-control study.

Background: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia-reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects.

Natural helix 9 mutants of PPARγ differently affect its transcriptional activity.

Objective: The nuclear receptor PPARγ is the master regulator of adipocyte differentiation, distribution, and function. In addition, PPARγ induces terminal differentiation of several epithelial cell lineages, including colon epithelia. Loss-of-function mutations in PPARG result in familial partial lipodystrophy subtype 3 (FPDL3), a rare condition characterized by aberrant adipose tissue distribution and severe metabolic complications, including diabetes.

A Single Complex Allele in a Patient With Partial Lipodystrophy.

Genetic lipodystrophies are a group of rare syndromes associated with major metabolic complications - including severe insulin resistance, type 2 diabetes mellitus, and hypertriglyceridemia - which are classified according to the distribution of adipose tissue. Lipodystrophies can be present at birth or develop during life and can range from local to partial and general. With at least 18 different genes implicated so far, definite diagnosis can be challenging due to clinical and genetic heterogeneity.

An oral mixed fat load is followed by a modest anti-inflammatory adipocytokine response in overweight patients with metabolic syndrome.

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.

The relation between body iron stores and adipose tissue function in patients with manifest vascular disease.

Background: 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.

Materials And Methods: 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.

Hepatocyte growth factor and interferon-γ inducible protein-10 are related to visceral adiposity.

Background: 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.

Objectives: 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.

Plasma triglyceride levels increase the risk for recurrent vascular events independent of LDL-cholesterol or nonHDL-cholesterol.

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.

Obesity and dyslipidemia.

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.

Obesity and dyslipidemia.

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.

Inherited lipodystrophies and the metabolic syndrome.

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.

Familial partial lipodystrophy phenotype resulting from a single-base mutation in deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-gamma.

Context: 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).

Objective: Our objective was to investigate whether the clinical phenotype of this proband is due to mutation(s) in PPARgamma.

Lipase H, a new member of the triglyceride lipase family synthesized by the intestine.

We report here the molecular cloning of a novel member of the triglyceride lipase family, a 2.4-kb cDNA encoding human lipase H (LIPH) and the mouse ortholog (Liph). The human LIPH cDNA encodes a 451-amino-acid protein with a lipase domain.

The apolipoprotein L gene cluster has emerged recently in evolution and is expressed in human vascular tissue.

We previously isolated APOL3 (CG12-1) cDNA and now describe the isolation of APOL1 and APOL2 cDNA from an activated endothelial cell cDNA library and show their endothelialspecific expression in human vascular tissue. APOL1-APOL4 are clustered on human chromosome 22q13.1, as a result of tandem gene duplication, and were detected only in primates (humans and African green monkeys) and not in dogs, pigs, or rodents, showing that this gene cluster has arisen recently in evolution.