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    472 results match your criteria Lipodystrophy Generalized

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    Metreleptin Treatment in Three Patients with Generalized Lipodystrophy.
    Clin Med Insights Case Rep 2016 5;9:123-127. Epub 2017 Jan 5.
    Mayo Clinic, Rochester, MN, USA.
    Generalized lipodystrophy (GL) is a rare inherited or acquired disease characterized by widespread loss of subcutaneous fat, leading to leptin deficiency, ectopic fat deposition, and severe metabolic abnormalities. Previous studies have shown the benefit of leptin replacement (metreleptin) in ameliorating metabolic complications, but little is known about the experience of metreleptin treatment outside of a research setting. We report on post-marketing clinical experience with metreleptin therapy in three patients with GL and marked hypoleptinemia, uncontrolled diabetes, and hypertriglyceridemia. Read More

    Clinical features and management of non-HIV related lipodystrophy in children: a systematic review.
    J Clin Endocrinol Metab 2016 Dec 14:jc20162271. Epub 2016 Dec 14.
    1 Evidence-based Practice Center, Mayo Clinic College of Medicine, Rochester, Minnesota, USA, 55905.
    Context: Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue, usually associated with insulin resistance-related conditions.

    Objective: We conducted a systematic review to synthesize existing data on clinical and metabolic features of lipodystrophy (age at onset < 18 years).

    Data Source: Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexed Citations from inception through January 2016. Read More

    The long road to leptin.
    J Clin Invest 2016 Dec 1;126(12):4727-4734. Epub 2016 Dec 1.
    Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients. Read More

    High incidence of BSCL2 intragenic recombinational mutation in Peruvian type 2 Berardinelli-Seip syndrome.
    Am J Med Genet A 2017 Feb 21;173(2):471-478. Epub 2016 Nov 21.
    Department of Pathology, University of Washington, Seattle, Washington.
    Congenital generalized lipodystrophy (CGL) is a genetically heterogeneous group of disorders characterized by the absence of functional adipose tissue. We identified two pedigrees with CGL in the community of the Mestizo tribe in the northern region of Peru. Five cases, ranging from 15 months to 7 years of age, presented with generalized lipodystrophy, muscular prominence, mild intellectual disability, and a striking aged appearance. Read More

    Lipodystrophy Syndromes.
    Endocrinol Metab Clin North Am 2016 Dec 6;45(4):783-797. Epub 2016 Oct 6.
    Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8537, USA. Electronic address:
    Lipodystrophies are heterogeneous disorders characterized by varying degrees of body fat loss and predisposition to insulin resistance and its metabolic complications. They are subclassified depending on degree of fat loss and whether the disorder is genetic or acquired. The two most common genetic varieties include congenital generalized lipodystrophy and familial partial lipodystrophy; the two most common acquired varieties include acquired generalized lipodystrophy and acquired partial lipodystrophy. Read More

    Characterization of a caveolin-1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy.
    Traffic 2016 Dec 2;17(12):1297-1312. Epub 2016 Nov 2.
    Department of Molecular Physiology and Biophysics, Vanderbilt School of Medicine, Nashville, Tennessee.
    Congenital generalized lipodystrophy (CGL) and pulmonary arterial hypertension (PAH) have recently been associated with mutations in the caveolin-1 ( CAV1 ) gene, which encodes the primary structural protein of caveolae. However, little is currently known about how these CAV1 mutations impact caveolae formation or contribute to the development of disease. Here, we identify a heterozygous F160X CAV1 mutation predicted to generate a C-terminally truncated mutant protein in a patient with both PAH and CGL using whole exome sequencing, and characterize the properties of CAV1 , caveolae-associated proteins and caveolae in skin fibroblasts isolated from the patient. Read More

    Cardiac Manifestations of Congenital Generalized Lipodystrophy.
    Clin Diabetes 2016 Oct;34(4):181-186
    Division of Cardiology, University of Texas Health Science Center at San Antonio and Audie L. Murphy VA Hospital, San Antonio, TX.
    IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder. Read More

    The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline.
    J Clin Endocrinol Metab 2016 Dec 6;101(12):4500-4511. Epub 2016 Oct 6.
    National Institute of Diabetes and Digestive and Kidney Diseases (R.J.B., K.I.R.), National Institutes of Health, Bethesda, Maryland 20892; Department of Medicine (D.A.-V.), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Paediatrics and Adolescent Medicine (P.T.C.), The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Paediatrics (D.D.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Metabolic Research Laboratories Wellcome Trust (D.D.), Medical Research Council (MRC) Institute of Metabolic Science, National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Division of Nutrition and Metabolic Diseases (A.G.), Department of Internal Medicine and the Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas 75390; Royal North Shore Hospital (M.J.), Northern Clinical School, University of Sydney, St Leonards, NSW 2126, Australia; Department of Paediatrics and Child Health (L.M.), University of Nairobi, 00100 Nairobi, Kenya; Brehm Center for Diabetes and Division of Metabolism, Endocrinology, and Diabetes (E.A.O.), Department of Internal Medicine, University of Michigan Medical School and Health Systems, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (N.P.), Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas 75390; Division of Pediatric Endocrinology and Diabetes (J.v.S., M.W.), Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany; Clamp Technologies Laboratory (E.S.), Endocrinology Research Center, and Laboratory of Molecular Endocrinology of Medical Scientific Educational Centre of Lomonosov, Moscow State University, Moscow 119991, Russia; Pediatric Endocrine Unit and Program in Nutritional Metabolism (T.S.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02115; Sorbonne Universities (C.V.), l'université Pierre et Marie Curie, University of Paris VI, Inserm Unité Mixte de Recherche en Santé 938, St-Antoine Research Center, Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, St-Antoine Hospital, Molecular Biology and Genetics Department, 75012 Paris, France; Department of Paediatric Endocrinology (R.W.), Cambridge University Hospitals NHS Trust, Cambridge CB2 0QQ, United Kingdom; and Division of Pediatric Endocrinology and Metabolism (T.Y.), Children's Medical Center, Osaka City General Hospital, Osaka City 534-0021, Japan.
    Objective: Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most clinicians are not familiar with their diagnosis and management. This practice guideline summarizes the diagnosis and management of lipodystrophy syndromes not associated with HIV or injectable drugs. Read More

    Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program.
    J Diabetes Metab 2016 Mar 23;7(3). Epub 2016 Mar 23.
    Brehm Center for Diabetes Research and Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
    Objective: Patients with lipodystrophy have severe metabolic abnormalities (insulin resistance, diabetes, and hypertriglyceridemia) that may increase morbidity and mortality. Metreleptin is approved by the United States Food and Drug Administration for treatment of generalized forms of lipodystrophy. We aimed to determine the efficacy and safety of metreleptin among patients with partial lipodystrophy using an expanded-access model. Read More

    Progressive Myoclonus Epilepsy in Congenital Generalized Lipodystrophy type 2: Report of 3 cases and literature review.
    Seizure 2016 Nov 5;42:1-6. Epub 2016 Sep 5.
    University Hospital of Verona, Department of Surgical Sciences, Gynecology and Pediatrics, Section of Child Neuropsychiatry, piazzale L.A. Scuro 10, 37134 Verona, Italy.
    Purpose: A small case series with a neurodegenerative disorder involving central nervous system and related to Seipin mutations was recently reported. Herein we describe clinical and EEG features of three patients presenting with Progressive Myoclonus Epilepsy (PME) and Congenital Generalized Lipodystrophy type 2 (CGL2) related to novel Seipin mutations.

    Methods: The EEG-clinical picture was evaluated at epilepsy onset and in the follow-up period. Read More

    Bone imaging findings in genetic and acquired lipodystrophic syndromes: an imaging study of 24 cases.
    Skeletal Radiol 2016 Nov 8;45(11):1495-506. Epub 2016 Sep 8.
    Rheumatology Department, Université Paris 06, DHU i2B, AP-HP, Saint-Antoine Hospital, 184, rue du Faubourg Saint-Antoine, 75012, Paris, France.
    Objective: To describe the bone imaging features of lipodystrophies in the largest cohort ever published.

    Materials And Methods: We retrospectively examined bone imaging data in 24 patients with lipodystrophic syndromes. Twenty-two had genetic lipodystrophy: 12/22 familial partial lipodystrophy (FPLD) and 10/22 congenital generalized lipodystrophy (CGL), 8 with AGPAT2-linked CGL1 and 2 with seipin-linked CGL2. Read More

    PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis.
    PLoS One 2016 9;11(9):e0162513. Epub 2016 Sep 9.
    Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
    Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. Read More

    Clinical and mutational features of three Chinese children with congenital generalized lipodystrophy.
    J Clin Res Pediatr Endocrinol 2016 Sep 9. Epub 2016 Sep 9.
    Objective: To investigate the clinical and molecular features of three Chinese patients with various typical manifestations of congenital generalized lipodystrophy (CGL).

    Methods: Clinical symptoms, results of laboratory analyses, and data on previous treatments in three Chinese patients were collected by retrospective review of medical records. All coding regions and adjacent exon-intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced. Read More

    Leptin and Hormones: Energy Homeostasis.
    Endocrinol Metab Clin North Am 2016 Sep;45(3):633-45
    Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, ST 820, Boston, MA 02215, USA. Electronic address:
    Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Read More

    Whole Exome Sequencing Reveals a BSCL2 Mutation Causing Progressive Encephalopathy with Lipodystrophy (PELD) in an Iranian Pediatric Patient.
    Iran Biomed J 2016 Nov 25;20(5):295-301. Epub 2016 Jul 25.
    Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
    Background: Progressive encephalopathy with or without lipodystrophy is a rare autosomal recessive childhood-onset seipin-associated neurodegenerative syndrome, leading to developmental regression of motor and cognitive skills. In this study, we introduce a patient with developmental regression and autism. The causative mutation was found by exome sequencing. Read More

    Assembly and Turnover of Caveolae: What Do We Really Know?
    Front Cell Dev Biol 2016 27;4:68. Epub 2016 Jun 27.
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of MedicineNashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of MedicineNashville, TN, USA; Epithelial Biology Program, Vanderbilt University School of MedicineNashville, TN, USA; Chemical and Physical Biology Program, Vanderbilt UniversityNashville, TN, USA.
    In addition to containing highly dynamic nanoscale domains, the plasma membranes of many cell types are decorated with caveolae, flask-shaped domains enriched in the structural protein caveolin-1 (Cav1). The importance of caveolae in numerous cellular functions and processes has become well-recognized, and recent years have seen dramatic advances in our understanding of how caveolae assemble and the mechanisms control the turnover of Cav1. At the same time, work from our lab and others have revealed that commonly utilized strategies such as overexpression and tagging of Cav1 have unexpectedly complex consequences on the trafficking and fate of Cav1. Read More

    Neuronal seipin knockout facilitates Aβ-induced neuroinflammation and neurotoxicity via reduction of PPARγ in hippocampus of mouse.
    J Neuroinflammation 2016 Jun 10;13(1):145. Epub 2016 Jun 10.
    State Key Laboratory of Reproductive Medicine, Hanzhong Road 140, Nanjing, 210029, China.
    Background: A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Seipin is highly expressed in hippocampal pyramidal cells and astrocytes. Neuronal knockout of seipin in mice (seipin-KO mice) reduces the hippocampal peroxisome proliferator-activated receptor gamma (PPARγ) level without the loss of pyramidal cells. Read More

    Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease.
    Mol Metab 2016 Jun 11;5(6):422-32. Epub 2016 Apr 11.
    Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
    Objective: Normal adipose tissue growth and function is critical to maintaining metabolic homeostasis and its excess (e.g. obesity) or absence (e. Read More

    Lipodystrophy Due to Adipose Tissue-Specific Insulin Receptor Knockout Results in Progressive NAFLD.
    Diabetes 2016 Aug 10;65(8):2187-200. Epub 2016 May 10.
    Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA
    Ectopic lipid accumulation in the liver is an almost universal feature of human and rodent models of generalized lipodystrophy and is also a common feature of type 2 diabetes, obesity, and metabolic syndrome. Here we explore the progression of fatty liver disease using a mouse model of lipodystrophy created by a fat-specific knockout of the insulin receptor (F-IRKO) or both IR and insulin-like growth factor 1 receptor (F-IR/IGFRKO). These mice develop severe lipodystrophy, diabetes, hyperlipidemia, and fatty liver disease within the first weeks of life. Read More

    Spectrum of clinical manifestations in two young Turkish patients with congenital generalized lipodystrophy type 4.
    Eur J Med Genet 2016 Jun 7;59(6-7):320-4. Epub 2016 May 7.
    Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, TX, USA.
    Congenital generalized lipodystrophy type 4 is an extremely rare autosomal recessive disorder. We report our clinical experience on two unrelated Turkish patients with congenital generalized lipodystrophy type 4. A 13-year-old girl (patient-1) presented with generalized lipodystrophy and myopathy. Read More

    Maladaptative Autophagy Impairs Adipose Function in Congenital Generalized Lipodystrophy due to Cavin-1 Deficiency.
    J Clin Endocrinol Metab 2016 Jul 4;101(7):2892-904. Epub 2016 May 4.
    From Sorbonne Universités, UPMC Univ Paris 6, and Inserm UMR_S938, Centre de Recherche St-Antoine, F-75012, Paris, France (L.S.-T., M.A., M.N., O.L., J.C., C.V.); Institute of Cardiometabolism and Nutrition (L.S.-T., M.A., O.L., J.C., C.V.), Groupe Hospitalier La Pitié-Salpêtrière, F-75013 Paris, France; Service d'Histologie et de Biologie Cellulaire (F.T.), Faculté de Médecine-Université de Limoges; AP-HP, Hôpital Tenon, Service de Biochimie et Hormonologie (J.C.), F-75020, Paris, France; Medical Genetics Center, Cairo, Egypt (S.M.E., E.E.); McGill University and Génome Québec Innovation Centre, Montréal, Canada (M.L.); Commissariat à l'Energie Atomique/Institut de Génomique/Centre National de Génotypage (M.D.), Evry, France; AP-HP, Hôpital St-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, F-75012, Paris, France (O.L., C.V.); and Inserm UMR_S1087, L'Institut du Thorax (J.M.), F-44007 Nantes, France.
    Context: Mutations in PTRF encoding cavin-1 are responsible for congenital generalized lipodystrophy type 4 (CGL4) characterized by lipoatrophy, insulin resistance, dyslipidemia, and muscular dystrophy. Cavin-1 cooperates with caveolins to form the plasma membrane caveolae, which are involved in cellular trafficking and signalling and in lipid turnover.

    Objective: We sought to identify PTRF mutations in patients with CGL and to determine their impact on insulin sensitivity, adipose differentiation, and cellular autophagy. Read More

    Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey.
    J Clin Endocrinol Metab 2016 Jul 4;101(7):2759-67. Epub 2016 May 4.
    Department of Internal Medicine (B.A., T.D., U.C., A.C.), Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey; Department of Medical Genetics (H.O., S.O.), Ege University, Izmir, Turkey; Department of Pediatrics (S.O.), Division of Pediatric Endocrinology, Ege University, Izmir, Turkey; Department of Medical Genetics (H.K., U.A.), Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; Department of Medical Genetics (H,K., A.A.), Koc University School of Medicine, Istanbul, Turkey; Division of Pediatric Neurology (G.A.), Dr. Behcet Uz Children's Hospital, Izmir, Turkey; Department of Pediatrics (B.N., E.M.), Division of Pediatric Genetics, Akdeniz University, Antalya, Turkey; Department of Pediatrics (B.T.), Division of Genetics, Istanbul Cerrahpasa University, Istanbul, Turkey; Division of Pediatric Endocrinology (M.N.O.), Diyarbakir Children's Hospital, Diyarbakir, Turkey; Department of Internal Medicine (A.G., H.B.S), Division of Endocrinology, Ataturk University, Erzurum, Turkey; Department of Internal Medicine (I.Y.S.), Division of Endocrinology, Ege University, Izmir, Turkey; Department of Radiology (C.A., M.S.), Dokuz Eylul University, Izmir, Turkey; Department of Biochemistry (L.D., F.S.), Ataturk Training Hospital, Izmir, Turkey; Department of Pediatrics (E.S.), Division of Pediatric Endocrinology, Osmangazi University, Eskisehir, Turkey; Department of Internal Medicine (M.A.), Division of Endocrinology, Yuzuncu Yil University, Van, Turkey; Department of Pediatrics (H.T.), Division of Pediatric Neurology, Hacettepe University, Ankara, Turkey; Department of Internal Medicine (H.A.), Division of Endocrinology, Ondokuz Mayis University, Samsun, Turkey; Department of Pediatrics (T.A.), Division of Pediatric Genetics, Ege University, Izmir, Turkey; and Department of Internal Medicine and the Center for Human Nutrition (A.G.), Division of Nutrition and Metabolic Diseases, UT Southwestern Medical Center, Dallas, Texas.
    Context: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat.

    Objective: We aimed to study natural history and disease burden of various subtypes of CGL.

    Design: We attempted to ascertain nearly all patients with CGL in Turkey. Read More

    Pseudoacromegaly in congenital generalised lipodystrophy (Berardinelli-Seip syndrome).
    BMJ Case Rep 2016 Apr 11;2016:10.1136/bcr-2016-214493. Epub 2016 Apr 11.
    Department of Endocrinology & Metabolism, Institute of Post-graduate Medical Education & Research/SSKM Hospital, Kolkata, West Bengal, India.
    Pseudoacromegaly, or acromegaloidism, is characterised by a clinical appearance mimicking acromegaly in the absence of documented hypersomatotropism or past exposure to excess growth hormone. It can develop secondary to a number of congenital and acquired conditions of which severe insulin resistance is an important example. Lipodystrophy syndromes are a group of rare disorders of which autosomal recessive congenital generalised lipodystrophy is the most common type. Read More

    Clinical and laboratory data of a large series of patients with congenital generalized lipodystrophy.
    Diabetol Metab Syndr 2016 15;8:23. Epub 2016 Mar 15.
    Instituto de Medicina Tropical do Rio Grande do Norte, Natal, Brazil ; Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN Brazil ; Institute of Science and Technology of Tropical Diseases, INCT-DT, Salvador, Brazil.
    Background: Berardinelli-Seip congenital lipodystrophy (BSCL) was initially described by Berardinelli in Brazil in 1954 and 5 years later by Seip in Norway. It is an autosomal recessive disease that leads to a generalized deficit of body fat, evolving with diabetes and hypertriglyceridemia. The aim of this study was to describe the clinical and laboratory characteristics of a large series of patients with BSCL. Read More

    Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations.
    Metabolism 2016 Apr 7;65(4):543-56. Epub 2016 Jan 7.
    Medical Innovation Center (MIC), Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:
    Objective: Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by marked scarcity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early-onset diabetes. Mutation of the BSCL2/SEIPIN gene causes the most severe form of CGL. The aim of this study was to generate induced pluripotent stem (iPS) cells from patients with CGL harboring BSCL2/SEIPIN mutations. Read More

    Progressive Generalized Lipodystrophy as a Manifestation of Autoimmune Polyglandular Syndrome Type 1.
    J Clin Endocrinol Metab 2016 Apr 18;101(4):1344-7. Epub 2016 Feb 18.
    Endocrinology Department (E.S.), IM Sechenov First Moscow State Medical University, 119991 Moscow, Russia; Outpatient Clinic (E.F.), Gastroenterology Department (D.R., S.P.), and Healthy and Sick Child Nutrition Department (E.R.), Scientific Center for Children's Health, 119991 Moscow, Russia; Department and Laboratory of Inherited Endocrine Disorders (E.V., V.P., A.T.), Endocrinology Research Centre, 117036 Moscow, Russia; and Laboratory of Molecular Endocrinology of Medical Scientific Educational Centre of Lomonosov (A.T.), Moscow State University, 119991 Moscow, Russia.
    We describe APS1 in a boy with generalized lipodystrophy, oral candidiasis, autoimmune hepatitis and adrenal insufficiency. It is the first time when generalized lipodystrophy is associated with APS1. Read More

    Acquired generalized lipodystrophy in a young lean Chinese girl. Case Report.
    Neuro Endocrinol Lett 2015 Dec;36(7):650-2
    Department of Endocrinology, Chinese PLA General Hospital, Beijing, China, China.
    Lipodystrophies is a really rare group of diseases characterized by altered body fat amount and/or repartition and serious insulin resistance.We reported a lean Chinese girl with acquired generalized lipodystrophy, who had a long history of poorly controlled diabetes mellitus (DM) despite with extremely high dose insulin (6 u/kg/d) therapy, combined with severe hypertriglyceridemia and acanthosis nigricans. The differential diagnosis of Lipodystrophies should be considered in lean patients presenting with early onset DM, combined with serious insulin resistance. Read More

    Successful cardiac transplantation in a patient with congenital generalized lipodystrophy.
    Pediatr Transplant 2016 Mar 29;20(2):321-4. Epub 2016 Jan 29.
    Congenital Heart Diseases and Pediatric Cardiology Unit, Cardiac Surgery Department, Complejo Hospitalario Universitario A Coruña, A Coruna, Spain.
    We report a case of a 12-yr-old boy referred to our unit with congenital generalized lipodystrophy and dilated cardiomyopathy related to a lamin gene mutation. He progressively developed end-stage heart failure and was referred for heart transplant evaluation. The patient's lipid profile, glucose level, and renal function were normal, and vascular retinopathy was ruled out. Read More

    Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.
    J Neurosci 2016 Jan;36(4):1242-53
    State Key Laboratory of Reproductive Medicine and Department of Physiology, Nanjing Medical University, Nanjing 210029, China,
    Unlabelled: A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). Read More

    [Genetics of congenital lipodystrophies].
    Ann Endocrinol (Paris) 2015 Oct;76(6 Suppl 1):S2-9
    Service d'Endocrinologie, Nutrition et Maladies Métaboliques, CHU Larrey, 24 Chemin de Pouvourville, TSA 30030, 31059 Toulouse, France.
    Congenital lipodystrophies are heterogeneous genetic diseases, leading to the loss of adipose tissue. This loss of adipose tissue can be generalized or partial, thus defining different phenotypes. These lipodystrophies have a major metabolic impact, secondary to lipotoxicity. Read More

    Diet rich in Docosahexaenoic Acid/Eicosapentaenoic Acid robustly ameliorates hepatic steatosis and insulin resistance in seipin deficient lipodystrophy mice.
    Nutr Metab (Lond) 2015 18;12:58. Epub 2015 Dec 18.
    Institute of Cardiovascular Sciences, Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, 38, XueYuan Road, HaiDian District, Beijing, 100191 People's Republic of China.
    Background: N-3 polyunsaturated fatty acids (n-3 PUFAs), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to effectively improve hepatic steatosis and insulin resistance caused by obesity. Lipodystrophy could also develop insulin resistance and hepatic steatosis. However, the effect of supplemental DHA/EPA to hepatic steatosis caused by lipodystrophy is unknown. Read More

    Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy.
    Clin Endocrinol (Oxf) 2016 Jul 2;85(1):137-49. Epub 2016 Feb 2.
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
    Objective: Recombinant human leptin (metreleptin) improves glycaemia and hypertriglyceridaemia in patients with generalized lipodystrophy; antibody development with in vitro neutralizing activity has been reported. We aimed to characterize antimetreleptin antibody development, including in vitro neutralizing activity.

    Design: Two randomized controlled studies in patients with obesity (twice-daily metreleptin ± pramlintide for 20-52 weeks; 2006-2009); two long-term, open-label studies in patients with lipodystrophy (once-daily or twice-daily metreleptin for 2 months to 12·3 years; 2000-2014). Read More

    One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes.
    Diabetes Obes Metab 2016 Jul 12;18(7):693-7. Epub 2016 Jan 12.
    Sorbonne Universités, UPMC, Univ Paris 06, Paris, France.
    Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v. Read More

    Metreleptin Treatment in Patients with Non-HIV Associated Lipodystrophy.
    Recent Pat Endocr Metab Immune Drug Discov 2015 ;9(2):74-8
    Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey.
    Lipodystrophies are a heterogeneous group of disorders characterized by congenital or acquired loss of adipose tissue. Recently, metreleptin, a recombinant human leptin analog, has been approved for the treatment of patients with generalized lipodystrophy. Leptin is an adipokine which has a fundamental role in glucose and lipid homeostasis. Read More

    Amenorrhea, ptosis and high insulin requirement in a young girl.
    Diabetes Metab Syndr 2016 Jan-Mar;10(1 Suppl 1):S151-3. Epub 2015 Oct 9.
    Department of Medicine, AFMC, Pune 411040, India.
    Lipodystrophy is an uncommon condition leading to excessive insulin requirement and menstrual abnormalities in young girls with diabetes. Neurological symptoms are uncommon in patients of generalized or partial lipodystrophy. We recently encountered a young girl, who presented with high insulin requirement, amenorrhea and neurological symptoms. Read More

    Asymmetric hypertrophic cardiomyopathy in generalized lipodystrophy.
    Int J Cardiol 2016 Jan 9;202:724-5. Epub 2015 Oct 9.
    Division of Cardiology, Ospedale Medico-Chirurgico Accreditato Villa dei Fiori, Acerra (Naples), Italy; Z. and M.A. Wiener Cardiovascular Institute and M.-J. and H.R. Kravis Center for Cardiovascular Health, Mount Sinai Medical Center, New York, NY, USA.

    Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.
    Expert Rev Clin Pharmacol 2016 14;9(1):59-68. Epub 2015 Oct 14.
    a Diabetes, Endocrinology, and Obesity Branch , National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health , Bethesda , MD , USA.
    The lipodystrophies represent a class of diseases characterized by leptin deficiency. Leptin deficiency is associated with a severe form of the metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and ovarian dysfunction. Metreleptin is the pharmaceutical derived product that has been approved by the Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Read More

    Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ.
    Dis Model Mech 2015 Dec 22;8(12):1615-24. Epub 2015 Sep 22.
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China Department of Physiology, Nanjing Medical University, Nanjing 210029, China
    The seipin gene (BSCL2) was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2). Neuronal seipin-knockout (seipin-nKO) mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG) and the underlying mechanisms of the effects. Read More

    New advances in the treatment of generalized lipodystrophy: role of metreleptin.
    Ther Clin Risk Manag 2015 16;11:1391-400. Epub 2015 Sep 16.
    Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
    Recombinant methionyl human leptin or metreleptin is a synthetic leptin analog that has been trialed in patients with leptin-deficient conditions, such as leptin deficiency due to mutations in the leptin gene, hypothalamic amenorrhea, and lipodystrophy syndromes. These syndromes are characterized by partial or complete absence of adipose tissue and hormones derived from adipose tissue, most importantly leptin. Patients deficient in leptin exhibit a number of severe metabolic abnormalities such as hyperglycemia, hypertriglyceridemia, and hepatic steatosis, which can progress to diabetes mellitus, acute pancreatitis, and hepatic cirrhosis, respectively. Read More

    A Report of Three Cases With Acquired Generalized Lipodystrophy With Distinct Autoimmune Conditions Treated With Metreleptin.
    J Clin Endocrinol Metab 2015 Nov 21;100(11):3967-70. Epub 2015 Sep 21.
    Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan 48109.
    Context: Acquired generalized lipodystrophy (AGL) is associated with leptin deficiency as a result of adipose tissue loss and hypertriglyceridemia, insulin resistance, and hepatic steatosis. It may coexist with other autoimmune diseases such as Hashimoto's thyroiditis, rheumatoid arthritis, hemolytic anemia, and chronic active hepatitis. Metreleptin therapy has been shown to improve metabolic abnormalities in lipodystrophy, but the effect on AGL patients with active autoimmune disease is unknown. Read More

    Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome in the context of inherited lipodystrophies.
    Metabolism 2015 Nov 1;64(11):1530-40. Epub 2015 Aug 1.
    Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy. Electronic address:
    Background: Lipodystrophies are a large heterogeneous group of genetic or acquired disorders characterized by generalized or partial fat loss, usually associated with metabolic complications such as diabetes mellitus, hypertriglyceridemia and hepatic steatosis. Many efforts have been made in the last years in identifying the genetic etiologies of several lipodystrophy forms, although some remain to be elucidated.

    Methods: We report here the clinical description of a woman with a rare severe lipodystrophic and progeroid syndrome associated with hypertriglyceridemia and diabetes whose genetic bases have been clarified through whole-exome sequencing (WES) analysis. Read More

    Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.
    Genome Med 2015 28;7:63. Epub 2015 Jun 28.
    MRC Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge, CB1 9NL UK ; Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge, UK.
    Background: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge.

    Methods: We compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls. Read More

    Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals.
    J Lipid Res 2015 Oct 12;56(10):1912-25. Epub 2015 Aug 12.
    Department of Physiology, Georgia Regents University, Augusta, GA 30912.
    Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis. Read More

    A Novel Syndrome of Generalized Lipodystrophy Associated With Pilocytic Astrocytoma.
    J Clin Endocrinol Metab 2015 Oct 7;100(10):3603-6. Epub 2015 Aug 7.
    Division of Pediatric Endocrinology (N.P., G.T.), Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas 75390; Hospital Universitario Prof. Edgard Santos (C.A.), Pediatric Endocrinology Unit, Faculty of Medicine Federal University of Bahia, 401157-190 Salvador, Bahia, Brazil; Division of Pediatric Endocrinology and Diabetes (J.v.S., M.W.), Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany; and Departments of Pathology and Pediatrics (D.R.), and Division of Nutrition and Metabolic Diseases, Department of Internal Medicine (A.G.), UT Southwestern Medical Center, Dallas, Texas 75390.
    Context: A rare presentation of hypothalamic tumors in infants and young children is profound emaciation and generalized loss of sc adipose tissue, also known as "diencephalic syndrome." Similar loss of sc fat can be observed in children with acquired generalized lipodystrophy or congenital generalized lipodystrophy. Precise diagnosis may be challenging early in the course of the disease, especially in the absence of metabolic abnormalities. Read More

    Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues.
    Nat Commun 2015 Aug 6;6:7808. Epub 2015 Aug 6.
    Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
    Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression and genetic determinants. Early MAT formation in mice is conserved, whereas later development is strain dependent. Read More

    Congenital generalized lipodystrophies--new insights into metabolic dysfunction.
    Nat Rev Endocrinol 2015 Sep 4;11(9):522-34. Epub 2015 Aug 4.
    Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8537, USA.
    Congenital generalized lipodystrophy (CGL) is a heterogeneous autosomal recessive disorder characterized by a near complete lack of adipose tissue from birth and, later in life, the development of metabolic complications, such as diabetes mellitus, hypertriglyceridaemia and hepatic steatosis. Four distinct subtypes of CGL exist: type 1 is associated with AGPAT2 mutations; type 2 is associated with BSCL2 mutations; type 3 is associated with CAV1 mutations; and type 4 is associated with PTRF mutations. The products of these genes have crucial roles in phospholipid and triglyceride synthesis, as well as in the formation of lipid droplets and caveolae within adipocytes. Read More

    Seipin deficiency increases chromocenter fragmentation and disrupts acrosome formation leading to male infertility.
    Cell Death Dis 2015 Jul 16;6:e1817. Epub 2015 Jul 16.
    1] Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA [2] Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA.
    The Berardinelli-Seip congenital lipodystrophy type 2 (Bscl2, seipin) gene is involved in adipogenesis. Bscl2-/- males were infertile but had normal mating behavior. Both Bscl2-/- cauda epididymis sperm count and sperm motility were ~20×less than control. Read More

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