Metreleptin (Myalepta) - leptin deficiency in lipodystrophy View of Metreleptin (Myalepta) | Canadian Journal of Health TechnologiesReturn to Article DetailsMetreleptin (Myalepta)
Metreleptin (Myalepta) - Leptin deficiency in lipodystrophy View of Metreleptin (Myalepta) | Canadian Journal of Health TechnologiesReturn to Article DetailsMetreleptin (Myalepta)
Setmelanotide (Imcivree) - Treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic pro-opiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) Published 16 January 2023 Statement of advice SMC2565 setmelanotide 10mg/mL solution for injection (Imcivree®) Rhythm Pharmaceuticals 09 December 2022 ADVICE : in the absence of a submission from the holder of the marketing authorisation setmelanotide (Imcivree®) is not recommended for use within NHSScotland. Indication under review: Treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic pro-opiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults
Metreleptin (Myalepta) - to treat the complications of leptin deficiency in lipodystrophy (LD) patients 1 Published 12 June 2023 1 SMC2559 metreleptin powder for solution for injection (Myalepta®) Amryt Pharmaceuticals DAC 5 May 2023 The Scottish Medicines Consortium (SMC) has completed its initial assessment of the evidence for the above product using the ultra-orphan framework: Indication under review: as an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy (LD) patients with: confirmed congenital generalised LD (Berardinelli-Seip syndrome) or acquired generalised LD (Lawrence syndrome) in adults and children 2 years of age and above. confirmed familial partial LD or acquired partial LD (Barraquer-Simons syndrome), in adults
Impact of high temperatures on enzyme-linked immunoassay (ELISA) performance for leptin measurements in human milk stored under varied freeze/thaw conditions. Ambient temperature conditions are a common concern during laboratory analysis. Due to unexpected shipping conditions, leptin ELISA kits (Leptin Ultrasensitive, ALPCO USA; Catalog #22-LEPHUU-E01) arrived from the manufacturer at our laboratory at a temperature (76.3°F/24.6°C) well above the 2-8°C conditions recommended by the manufacturer. Since no data are available on the effects of high ambient temperature exposure on the performance of this commercial assay, we opportunistically assessed assay performance using human milk samples. Leptin measurement of recently collected and frozen human milk samples was compared between the warm
The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients. Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy. In 121 patients with advanced NSCLC without mutations
The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders. Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. Prospective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin
The Impact of Gastric Leptin and Leptin Receptor Expression on Metabolic Outcomes Post Laparoscopic Sleeve Gastrectomy. Obesity is a growing global crisis, with predictions that nearly half of the world's population will be overweight or with severe obesity by 2030. Metabolic bariatric surgery, effective for those unable to lose weight through conventional methods, results in significant weight loss and alleviates associated medical problems. This study investigates changes in gastric leptin (LE) and leptin receptor (LER) expression following laparoscopic sleeve gastrectomy (LSG) and explores their metabolic contributions to surgical outcomes. Immunohistochemical staining for LE and LER was performed on gastric tissue biopsies from 54 patients pre- and post-LSG. Expression levels were
Dietary lipids shape cytokine and leptin profiles in obesity-metabolic syndrome implications: A cross-sectional study. Obesity, characterized by chronic energy imbalance and excessive adiposity, is a key component of metabolic syndrome and is associated with low-grade inflammation and altered adipokine secretion. This study aimed to evaluate the association between dietary fat consumption and its influence on interleukin (IL) and leptin levels in participants with obesity. Using the Asian obesity classification criteria, a cross-sectional study was conducted on 384 adults (18-59 years). Anthropometric measurements by bioelectrical impedance analyzer (BIA), blood biochemistry by colorimetric assay, inflammatory markers and hormones by ELISA test, and dietary intake were assessed by Semi
Leptin and leptin receptor expression as biomarkers for breast cancer: a retrospective study. Effective screening and treatment have reduced the number of women dying from breast cancer (BC). However, the long-term sequelae of BC treatment and psychosocial factors seriously affect the life quality of BC patients and survivors. Therefore, the discovery and application of targeted biomarkers to improve the functional outcome and life quality of BC patients is necessary. To explore the impact of leptin (LEP)/ leptin receptor (LEPR) expression on occurrence and survival of BC. Totally 132 primary BC and 66 non-BC patients who underwent surgery in department of breast surgery in Shanxi Cancer Hospital from January to October in 2009 were enrolled in this retrospective study. LEP and LEPR were
Glucose-dependent insulinotropic polypeptide counteracts diet-induced obesity along with reduced feeding, elevated plasma leptin and activation of leptin-responsive and proopiomelanocortin neurons in the arcuate nucleus. To clarify the effects of glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (GIPRAs) on feeding and body weight. Acute and subchronic effects of subcutaneous GIPFA-085, a long-acting GIPRA, on blood glucose, food intake, body weight, respiratory exchange ratio and plasma leptin levels were measured in diet-induced obese (DIO) mice and/or functional leptin-deficient ob/ob mice. The effects of GIPFA-085 on the hypothalamic arcuate nucleus (ARC) neurons from lean and DIO mice were studied by measuring cytosolic Ca concentration ([Ca ] ). Single bolus GIPFA
Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency. Deficiency in the adipose-derived hormone leptin or leptin receptor signaling causes class 3 obesity in individuals with genetic loss-of-function mutations in leptin or its receptor LEPR and metabolic and liver disease in individuals with hypoleptinemia secondary to lipoatrophy such as in individuals with generalized lipodystrophy. Therapies that restore leptin-LEPR signaling may resolve these metabolic sequelae. We developed a fully human monoclonal antibody (mAb), REGN4461 (mibavademab), that activates the human LEPR in the absence or presence of leptin. In obese leptin knockout mice, REGN4461 normalized body weight, food intake, blood glucose
Expression of leptin receptor in renal tubules is sparse but implicated in leptin-dependent kidney gene expression and function. Leptin regulates energy balance via leptin receptors expressed in central and peripheral tissues, but little is known about leptin-sensitive kidney genes, and the role of tubular leptin receptor (Lepr) in response to a high fat diet (HF). Quantitative RT-PCR analysis of Lepr splice variants A, B and C revealed a ratio of ~100:10:1 in mouse kidney cortex and medulla with medullary levels being ~10x higher. Leptin replacement in ob/ob mice for 6 days reduced hyperphagia, hyperglycemia and albuminuria, associated with normalization of kidney mRNA expression of molecular markers of glycolysis, gluconeogenesis, amino acid synthesis and Megalin. Normalization of leptin
Leptin Receptor Deficiency-Associated Diabetes Disrupts Lacrimal Gland Circadian Rhythms and Contributes to Dry Eye Syndrome. This study investigated the impact of hyperglycemia in type 2 diabetes mellitus (T2DM) on the circadian rhythms and function of lacrimal glands (LGs) in contributing to dry eye syndrome. We assessed the effects of hyperglycemia on circadian gene expression, immune cell
Apolipoprotein CIII correlates with lipoproteins in the fed state and is not regulated by leptin administration in states of hypoleptinemia induced by acute or chronic energy deficiency: Results from two randomised controlled trials. Medications targeting the leptin and Apolipoprotein CIII (APOC3) pathways are currently under development for the treatment of hypertriglyceridaemia. Given distinct conditions, each lasting 72 h: isocaloric feeding, fasting with placebo administration and fasting with leptin administered at replacement doses. In Study-2, 20 females with hypoleptinemia due to relative energy deficiency in sport (REDs) for a minimum of 6 months were treated with either leptin or a placebo for 36 weeks. In Study-1, APOC3 levels remained stable across all arms and were
Leptin Enhances M1 Macrophage Polarization and Impairs Tendon-Bone Healing in Rotator Cuff Repair: A Rat Model. Rotator cuff tears are common, affecting more than 60% of individuals older than 80 years, and they have been implicated in 70% of patients with shoulder pain. M1 polarization-related inflammation has been reported to be associated with poor healing outcomes of rotator cuff injury , and leptin, an adipokine, has been reported to be a potential activator of inflammation. However, whether leptin affects rotator cuff repair remains unknown. Using in vitro cell experiments and an in vivo rat rotator cuff tear model, we therefore asked: (1) Does leptin promote the M1 polarization of macrophages in vitro and in vivo? (2) Does leptin impair biomechanical strength, the histologic structure
Ablation of Leptin Receptor Signaling Alters Somatotrope Transcriptome Maturation in Female Mice. Anterior pituitary somatotropes respond to metabolic signals from the adipokine leptin to optimize functional responses to the body's nutritional state via growth hormone (GH) secretion. Molecular targets of leptin in pituitary somatotropes include GH, the GH-releasing hormone receptor (GHRHR ), and, in females, the transcription factor POU1F1, all of which are dependent on leptin stimulation for expression. To identify the trophic mechanisms underlying leptin action upon somatotropes, we analyzed single-cell gene transcriptomes comparing pituitaries from a female mouse model bearing somatotropes lacking leptin receptors (LEPR-null mutants) and control pituitaries. Computational clustering of results
Anti-obesity pharmacotherapy for patients with genetic obesity due to defects in the leptin-melanocortin pathway. Lifestyle interventions are the cornerstone of obesity treatment. However, insufficient long-term effects are observed in patients with genetic obesity disorders, as their hyperphagia remains untreated. Hence, patients with genetic obesity often require additional pharmacotherapy
Serum choline, leptin and interleukin-6 levels in fibromyalgia syndrome-induced pain: a case-control study. Fibromyalgia Syndrome (FMS) predominantly affects middle-aged women, characterized by musculoskeletal pain, fatigue, and cognitive issues. Choline, an endogenous molecule, may influence FMS due to its analgesic and anti-inflammatory properties. This study compared choline, leptin , and interleukin-6 (IL-6) levels in FMS patients and controls and examining their association with pain severity. Volunteers with FMS were clinically diagnosed at a Physical Medicine and Rehabilitation Department. The control group included pain-free volunteers. Pain severity was gauged using a numeric scale, dietary choline intake through a questionnaire. Serum choline, leptin and (interleukin)IL-6 levels were
Leptin and Iinterlukin-6 relationship and influence of mortality in sepsis. Sepsis is a severe and life-threatening disease involving multiple risk factors. Leptin has been suggested to play a role in modulating the inflammatory response in sepsis and improving outcomes; however, there are conflicting results regarding the outcome of sepsis. The present study aims to clarify the expression of leptin in patients with sepsis, and its association with other cytokines. The retrospective study enrolled 165 adults with sepsis from medical intensive care units (ICU)s, and collected leptin, glucose levels, and cytokines such as IL-6, IL-1RA, IL-10, IL-17, TNF-α, IFN-γfor analysis. Leptin levels were divided into three groups based on concentration: Low (≤ 3.78 ng/mL), Medium (3.78 < leptin ≤ 23.2