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Neonatal manifestation of multiple sulfatase deficiency.

INTRODUCTION: Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. CASE REPORT: We report clinical, biochemical, and molecular findings in a female newborn affected with a severe form of multiple sulfatase deficiency (Mendelian Inheritance in Man (MIM) # 272200). She presented with primary microcephaly, facial anomalies including depressed nasal bridge, nasal hypoplasia, anteverted nostrils, smooth philtrum, limited mobility of hip and knee joints, mild ichthyosis, as well as muscular hypotonia. The diagnosis is base

Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation.

OBJECTIVE: Short-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation. DESIGN: Randomised placebo-controlled study. METHODS: In this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36  h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5  pmol/kg per min)

[Citrate content in the myocardium and liver of rabbits in starvation and thyrotoxicosis].

Under starvation in rabbit blood plasma an increase in content of free fatty acids was accompanied by accumulation of citrate in myocardium and by maintenance of glycogen content in the organ. Contents of glycogen and citrate were decreased in liver tissue. In blood plasma under thyreotoxicosis an increase in concentration of free fatty acids was followed by decrease in contents of glycogen and citrate both in myocardium and in liver tissue. Under thyreotoxicosis the absence of the glycogenolysis block was associated with non-accumulation of citrate in myocardium. Difference in metabolic patte

Alkaline phosphatase superfamily members: new pieces of the choline metabolism puzzle.

Choline is an essential nutrient required for the synthesis of key molecules, such as phosphatidylcholine, sphingomyelin, acetylcholine, and S-adenosylmethionine. Choline metabolism encompasses two phases, namely the postprandial and postabsorptive states. The former enables the digestion, absorption, distribution, and storage of choline derivatives after a meal, while the latter allows the cellular utilization of choline and the mobilization of stored choline-containing molecules during fasting. Understanding choline metabolism is fundamental to the study of lipid disorders such as steatohepa

Role of annexin A7 in the occurrence and progression of coronary atherosclerosis: a narrative review.

BACKGROUND AND OBJECTIVE: Cardiovascular diseases, particularly coronary atherosclerosis, pose a major health burden, with plaque rupture and erosion contributing to acute coronary syndrome (ACS). Platelet adhesion and aggregation are key in thrombosis, making them critical therapeutic targets. This study aimed to elucidate the regulatory role of annexin A7 (ANXA7) in the progression of coronary atherosclerosis. METHODS: A literature review was performed using PubMed and Google Scholar. Clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews were consider

SGLT2 Inhibitors: From Structure-Effect Relationship to Pharmacological Response.

SGLT2 inhibitors have become increasingly used due to their effectiveness in improving not only type 2 diabetes but also cardiovascular, renal and hepatic diseases, as well as the obesity found in metabolic syndrome. Starting from the structure of gliflozins, modifications of the carbohydrate part, aglycone, and also the glycosidic bond between them can determine variations in pharmacokinetic and pharmacodynamic properties. SGLT2 inhibitors, in addition to reducing blood glucose levels, improve alterations in lipid metabolism by diverting excessively accumulated lipids in tissues towards mobil

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… Through the caloric deficit created and by facilitating lipid mobilization in tissues, gliflozins enhance obesity management. All these effects contribute to an improvement in patients’ quality of life and physical condition, thereby also demonstrating anti-aging properties. …

Alleviation of Hepatic Steatosis by Alpha-Defensin Is Associated with Enhanced Lipolysis.

Background and Objectives: The neutrophilic peptide, alpha-defensin, is considered an evolving risk factor intimately linked with lipid mobilization. It was previously linked to augmented liver fibrosis. Here, we assess a potential association between alpha-defensin and fatty liver. Materials and Methods: A cohort of transgenic C57BL/6JDef+/+ male mice that overexpress the human neutrophil-derived alpha-defensin in their polymorphonuclear neutrophils (PMNs) were assessed for liver steatosis and fibrosis development. Wild type (C57BL/6JDef.Wt) and transgenic (C57BL/6JDef+/+) mice were maintaine…

Combining Dietary Intervention with Metformin Treatment Enhances Non-Alcoholic Steatohepatitis Remission in Mice Fed a High-Fat High-Sucrose Diet.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are serious health concerns for which lifestyle interventions are the only effective first-line treatment. Dietary interventions are effective in body weight reduction, but not in improving insulin sensitivity and hepatic lipid mobilization. Conversely, metformin increases insulin sensitivity and promotes the inhibition of de novo hepatic lipogenesis. In this study, we evaluated the metformin effectiveness in NASH prevention and treatment, when combined with dietary intervention in male mice fed a high-fat high-…

OPA1 Regulates Lipid Metabolism and Cold-Induced Browning of White Adipose Tissue in Mice.

Mitochondria play a vital role in white adipose tissue (WAT) homeostasis including adipogenesis, fatty acid synthesis, and lipolysis. We recently reported that the mitochondrial fusion protein optic atrophy 1 (OPA1) is required for induction of fatty acid oxidation and thermogenic activation in brown adipocytes. In the current study we investigated the role of OPA1 in WAT function in vivo. We generated mice with constitutive or inducible knockout of OPA1 selectively in adipocytes. Studies were conducted under baseline conditions, at thermoneutrality, following high-fat feeding or during cold e

CIDEC/FSP27 is regulated by peroxisome proliferator-activated receptor alpha and plays a critical role in fasting- and diet-induced hepatosteatosis.

UNLABELLED: The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC; also known in rodents as FSP27 or fat-specific protein 27) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage. CIDEC/Fsp27 is highly expressed in adipose tissue, but undetectable in normal liver. However, its hepatic expression rises during fasting or under genetic or diet-induced hepatosteatosis in both mice and patients. Herein, we demonstrate that CIDEC/Fsp27 is a direct transcriptional target of the nuclear receptor PPARα (peroxisome proliferator-activated re

Platelet-activating factor: a putative neuromodulator and mediator in the pathophysiology of brain injury.

Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]) is a potent lipid autocoid produced by many cell types. PAF is produced by cultured rat cerebellar neurons and human fetal brain cells, and has been extracted from brain tissue. Multiple PAF receptors have been demonstrated in brain tissue. PAF stimulates intracellular Ca2+ mobilization and phosphatidylinositol (PI) metabolism in transformed neuronal cell lines via the PAF receptor, to which both pertussis toxin (PTX)-sensitive and -insensitive G protein appear to couple. PAF has potent actions on cerebral ve

Geochemical Mobility of Elements in Antarctic Environments Affected by CO2-Rich Hydrothermal Fluids: Astrobiological Implications.

Hydrothermal systems are widespread in our solar system. Identification of alteration mineral assemblages on Mars and potentially in ocean worlds such as Enceladus suggests the existence of extensive hydrothermal fluid-igneous rock interactions of astrobiological interest in different planetary bodies. Here, we studied the terrestrial analog Cerro Caliente, a band of geothermal alterations located in the glaciovolcanic environment of Deception Island (Antarctica), with the aim of determining the mobility of major chemical elements (e.g., alkalis, phosphorus) and its implications in the habitab

Mepce Restrains Ferroptosis in Prostate Cancer Through 7SK-P-TEFb Pause Control.

Ferroptosis can be therapeutically induced through GPX4 inhibition, but the mechanisms that determine ferroptosis sensitivity in prostate cancer remain incompletely understood. Here, we combined genome-wide CRISPR screening under graded GPX4 inhibition with mechanistic perturbation-rescue experiments and validation in xenograft and immunocompetent syngeneic prostate cancer models. We identified MEPCE loss as a conserved sensitizer to ferroptosis. Mechanistically, MEPCE depletion destabilized RN7SK and disrupted the HEXIM1-P-TEFb complex, consistent with CDK9 release and enhanced RNA polymerase

Refractory Gastric Antral Vascular Ectasia as a Sentinel for "Burned-Out" Metabolic Dysfunction-Associated Steatotic Liver Disease and Rapid Hepatocellular Carcinoma Progression in a Post-transcatheter Aortic Valve Implantation Dialysis Patient.

Gastric antral vascular ectasia (GAVE) is challenging to manage in multimorbid patients, where etiology varies between cirrhosis, autoimmune … le fibrosis. This "pseudo-normalization", likely driven by fibrosis replacing fat and tumor-induced lipid mobilization, masked the underlying pathology. Eight months post-bleeding (December 2023), clinical deterioration revealed decompensated cirrhosis and a massive 6.7 cm hepatocellular carcinoma (HCC). Diagnostic obscurity caused by steatosis resolution in "burned …

Menopause as a Critical Turning Point in Lipedema: The Estrogen Receptor Imbalance, Intracrine Estrogen, and Adipose Tissue Dysfunction Model.

Lipedema is a chronic, estrogen-sensitive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, fibrosis, inflammation, and resistance to fat mobilization. Despite its high prevalence, lipedema remains poorly understood and frequently misdiagnosed. This narrative review proposes a novel pathophysiological model in which menopause acts as a critical turning point in the progression of lipedema, driven by estrogen receptor imbalance (ERβ predominance over ERα), intracrine estrogen excess, and adipose tissue dysfunction. We demonstrate how menopause amplifies ad

Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics.

In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the i

Uroguanylin Action in the Brain Reduces Weight Gain in Obese Mice via Different Efferent Autonomic Pathways.

The gut-brain axis is of great importance in the control of energy homeostasis. The identification of uroguanylin (UGN), a peptide released … athways. On one hand, brain UGN induces brown adipose tissue thermogenesis, as well as browning and lipid mobilization in white adipose tissue through stimulation of the sympathetic nervous system. On the other hand, brain UGN augments fecal output through the vagus nerve. These findings are of relevance as they suggest that the beneficial metabolic actions of UGN t …

Rituximab inhibits B-cell receptor signaling.

Rituximab (RTX), a monoclonal antibody directed against the CD20 protein, is a drug commonly used in the treatment of B-cell-derived lymphoid neoplasias and of antibody-mediated autoimmune diseases. In addition to cell- and complement-mediated B-cell depletion, RTX is thought to inhibit B-cell survival and proliferation through negative regulation of canonical signaling pathways involving Akt, ERK, and mammalian target of rapamycin. However, surprisingly, although B-cell receptor (BCR) signaling has been considered critical for normal and more recently, for neoplastic B cells, the hypothesis t

Melanin-concentrating hormone-1 receptor antagonism and anti-obesity effects of ethanolic extract from Morus alba leaves in diet-induced obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In Korea, Morus alba leaves have been traditionally administered as natural therapeutic agent for the alleviating dropsy and diabetes. AIM OF THE STUDY: The present study was performed to evaluate melanin-concentrating hormone receptor subtype 1 (MCH1) antagonism of the ethanol extract of Morus alba leaves (EMA) and its anti-obesity effect in diet-induced obese (DIO) mice. MATERIALS AND METHODS: The binding affinity of EMA for the MCH1 receptor with europium-labeled MCH (Eu-MCH), the function of recombinant MCH1 receptors expressed in CHO cells, and the anti-o

Comprehensive Insights into the Cholesterol-Mediated Modulation of Membrane Function Through Molecular Dynamics Simulations.

Cholesterol plays an essential role in biological membranes and is crucial for maintaining their stability and functionality. In addition to biological membranes, cholesterol is also used in various synthetic lipid-based structures such as liposomes, proteoliposomes, and nanodiscs. Cholesterol regulates membrane properties by influencing the density of lipids, phase separation into liquid-ordered (Lo) and liquid-disordered (Ld) areas, and stability of protein-membrane interactions. For planar bilayers, cholesterol thickens the membrane, decreases permeability, and brings lipids into well-order