Disrupted-in-schizophrenia 1 Protein Misassembly Impairs Cognitive Flexibility and Social Behaviors in a Transgenic Rat Model.

Alterations in cognitive functions, social behaviors and stress reactions are commonly diagnosed in chronic mental illnesses (CMI). Animal models expressing mutant genes associated to CMI represent either rare mutations or those contributing only minimally to genetic risk. Non-genetic causes of CMI can be modeled by disturbing downstream signaling pathways, for example by inducing protein misassembly or aggregation.

The adipo-fibrokine activin A is associated with metabolic abnormalities and left ventricular diastolic dysfunction in obese patients.

Aims: Left ventricular diastolic dysfunction (LVDD) is common in obese subjects, and a relationship between epicardial adipose tissue (EAT), increased adipocytokines, and cardiovascular diseases has been reported. This study sought to examine as to whether the adipo-fibrokine activin A is a link between increased EAT, the metabolic syndrome (MetS), and LVDD in severely obese subjects.

Methods And Results: In 236 obese subjects (ø body mass index 39.

Aβ dimers induce behavioral and neurochemical deficits of relevance to early Alzheimer's disease.

We examined behaviors and neurotransmitter levels in the tgDimer mouse, a model for early Alzheimer's disease, that expresses exclusively soluble amyloid beta (Aβ) dimers and is devoid of Aβ plaques, astrogliosis, and neuroinflammation. Seven-month-old mice were subjected to tests of motor activity, attention, anxiety, habituation learning, working memory, and depression-related behaviors. They were impaired in nonselective attention and motor learning and showed anxiety- and despair-related behaviors.

Chronic corticosterone treatment enhances extinction-induced depression in aged rats.

Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID).

Interaction of epoxyeicosatrienoic acids and adipocyte fatty acid-binding protein in the modulation of cardiomyocyte contractility.

Background: Adipocyte fatty acid-binding protein (FABP4) is a member of a highly conserved family of cytosolic proteins that bind with high affinity to hydrophobic ligands, such as saturated and unsaturated long-chain fatty acids and eicosanoids. Recent evidence has supported a novel role for FABP4 in linking obesity with metabolic and cardiovascular disorders. In this context, we identified FABP4 as a main bioactive factor released from human adipose tissue that directly suppresses heart contraction in vitro.

WISP1 is a novel adipokine linked to inflammation in obesity.

WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine.

Changes in morphology and function of adrenal cortex in mice fed a high-fat diet.

Background/objectives: Obesity is a major risk factor for the development of type 2 diabetes and other debilitating diseases. Obesity and diabetes are intimately linked with altered levels of adrenal steroids. Elevated levels of these hormones induce insulin resistance and cause cardiovascular diseases.

Adipocyte fatty acid-binding protein levels are associated with left ventricular diastolic dysfunction in morbidly obese subjects.

Objectives: This study aimed to examine the association of adipocyte fatty acid-binding protein (FABP4) levels with left ventricular diastolic dysfunction (LVDD) in obese subjects with varying degrees of the metabolic syndrome (MetS).

Methods: Fifty morbidly obese subjects with LVDD were selected at random and matched by age (±5 years) and sex with 50 morbidly obese with normal left ventricular (LV) function. In addition, 24 healthy lean subjects were included as controls.

Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes.

Background: Fatty acid binding protein 4 (FABP4) is a predominantly cytosolic protein of the adipocytes, but also abundantly present in human plasma; its plasma concentrations were linked to obesity and metabolic syndrome. Recent studies have suggested a direct extracellular effect of FABP4 in the regulation of glucose metabolism and heart function independently of its effect as a carrier protein. Interestingly, FABP4 has no secretory signal sequence; hence, the mechanisms how FABP4 is released from adipocytes are unclear.

Lipoproteins and Hedgehog signalling--possible implications for the adrenal gland function.

Background: Metabolic syndrome is a common metabolic disorder that is associated with an increased risk of type 2 diabetes and cardiovascular diseases. Disturbances in adrenal steroid hormone production significantly contribute to the development of this disorder. Therefore, it is extremely important to fully understand the mechanisms governing adrenal gland function, both in physiological and pathological conditions.

Fatty acid binding protein 4 predicts left ventricular mass and longitudinal function in overweight and obese women.

Objective: To explore whether increased adipocyte-derived serum fatty acid binding protein 4 (FABP4) predisposes to cardiac remodelling and left ventricular dysfunction in human obesity.

Design: Cross-sectional investigation.

Setting: Academic clinical research centre.

Lipoprotein apheresis reduces adipocyte fatty acid-binding protein serum levels.

Background And Methods: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family highly expressed in adipocytes and macrophages. Recent studies indicate a key role for circulating FABP4 in the pathogenesis of atherosclerosis and type 2 diabetes. We described an additional role for FABP4 in the development of cardiac dysfunction in obesity.

Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters.

Roux-en-Y gastric bypass (RYGB) has become a prominent therapeutic option for long-term treatment of morbid obesity and type 2 diabetes mellitus (T2D). Cross talk and pathogenetic consequences of RYGB-induced profound effects on metabolism and gut microbiome are poorly understood. The aim of the present study therefore was to characterize intra-individual changes of gut microbial composition before and 3 months after RYGB by metagenomic sequencing in morbidly obese patients (body mass index (BMI)>40 kg m(-)(2)) with T2D.

BMS309403 directly suppresses cardiac contractile function.

BMS309403, a substance used as an inhibitor of adipocyte fatty acid-binding protein, has been suggested as a new therapeutic agent for treating type 2 diabetes mellitus and atherosclerosis; however, little is known about its possible side effects. The present study investigates the effects of BMS309403 on the cardiovascular system. We used isolated perfused heart preparations and single cardiomyocytes from adult rats for contractile analysis.

Adipocyte-derived factors suppress heart contraction.

Background: Obesity is strongly associated with cardiovascular diseases including systemic hypertension, coronary artery disease and heart failure. Despite several investigations the pathophysiological mechanisms involved remain unclear. We have previously shown that adipose tissue exerts a highly potent activity with an acute depressant effect on cardiomyocytes, thus suggesting direct involvement of adipose tissue in the development of heart dysfunction.

Expression and function of endocannabinoid receptors in the human adrenal cortex.

Endogenous cannabinoids are important signaling molecules in neuroendocrine control of homeostatic and reproductive functions including stress response and energy metabolism. The hypothalamic paraventricular and supraoptic nuclei have been shown to release endocannabinoids, which act as retrograde messengers to modulate the synaptic release of glutamate during stress response. This study endeavors to elucidate possible interaction of the endocannabinoid system with the regulation of adrenocortical function at the adrenal level.

Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease.

Rationale: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family and is predominantly expressed in adipose tissue. Emerging evidence suggests that FABP4 plays a role in some aspects of the metabolic syndrome including the development of type 2 diabetes and atherosclerosis. We have recently reported that secretory products from human adipocytes directly and acutely depressed cardiac contractile function.

Human adipocyte-derived factors directly inhibit cardiac contraction.

Obesity is a major risk factor for metabolic syndrome and cardiovascular disorders. Obesity related heart disease is the most serious complication of human obesity. Despite several investigations the pathophysiological mechanisms involved remain unclear.

Adrenocortical changes and arterial hypertension in lipoatrophic A-ZIP/F-1 mice.

The A-ZIP/F-1 transgenic mouse is a model of lipoatrophic diabetes with severe insulin resistance, hyperglycemia and hyperlipidemia. Recently, a regulatory role of adipose tissue on adrenal gland function and blood pressure has been suggested. To further explore the importance of adipose tissue in the regulation of adrenal function and blood pressure, we studied this mouse model of lipodystrophy.

Evidence for hemispheric specialization in the marmoset (Callithrix penicillata) based on lateralization of behavioral/neurochemical correlations.

A correlative study between behavioral, neurochemical and hormonal measures was conducted on male black tufted-ear marmoset monkeys (Callithrix penicillata). Behavioral analysis was performed in order to examine the effects of confrontation with a natural predator (taxidermized oncilla cat, Felis tigrina). The subjects were subjected to four trials without predator, six confrontation trials with predator present, and four trials with the predator removed.

Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II-sensitization in human adrenocortical cells.

Objectives: Hypertension is a major complication of overweight with frequently elevated aldosterone levels in obese patients. Our previous work suggests a direct stimulation of adrenal aldosterone secretion by adipocytes. Owing to aldosterone's important role in maintaining blood pressure homeostasis, its regulation in obesity is of major importance.

Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt-signaling pathway.

Context: Obesity is associated with hypersecretion of cortisol and aldosterone and a high prevalence of arterial hypertension. At the cellular level, a direct effect of adipocytes on the expression of the steroidogenic acute regulatory (StAR) protein, a regulator of cortisol and aldosterone synthesis, and on aldosterone and cortisol secretion has been shown. However, the molecular mechanisms mediating this effect are not known.

Insulin resistance in hypertension and cardiovascular disease.

Insulin resistance is not simply a problem of decreased glucose uptake in response to insulin, but a multifaceted syndrome that significantly increases the risk for cardiovascular disease. Insulin resistance is strongly associated with arterial hypertension and a pathogenetic role in the development of arterial hypertension has been suggested. One question that remains open concerns the clinical approach to insulin-resistant patients.

Increased aldosterone/renin quotient in obese hypertensive women: a novel role for low-density lipoproteins?

Obesity, especially visceral obesity, is strongly associated with arterial hypertension. Indeed, obesity hypertension has to be considered as the most common form of essential hypertension. However, the exact nature of the relationship between obesity and increased blood pressure remains poorly understood.