Lipodystrophy: A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.Lipodystrophy, Congenital Generalized: Congenital disorders, usually autosomal recessive, characterized by severe generalized lack of ADIPOSE TISSUE, extreme INSULIN RESISTANCE, and HYPERTRIGLYCERIDEMIA.HIV-Associated Lipodystrophy Syndrome: Defective metabolism leading to fat maldistribution in patients infected with HIV. The etiology appears to be multifactorial and probably involves some combination of infection-induced alterations in metabolism, direct effects of antiretroviral therapy, and patient-related factors.Lipodystrophy, Familial Partial: Inherited conditions characterized by the partial loss of ADIPOSE TISSUE, either confined to the extremities with normal or increased fat deposits on the face, neck and trunk (type 1), or confined to the loss of SUBCUTANEOUS FAT from the limbs and trunk (type 2). Type 3 is associated with mutation in the gene encoding PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA.Diabetes Mellitus, Lipoatrophic: A type of diabetes mellitus that is characterized by severe INSULIN RESISTANCE and LIPODYSTROPHY. The latter may be generalized, partial, acquired, or congenital (LIPODYSTROPHY, CONGENITAL GENERALIZED).Lamin Type A: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder.GTP-Binding Protein gamma Subunits: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN BETA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.1-Acylglycerol-3-Phosphate O-Acyltransferase: An enzyme that catalyzes the acyl group transfer of ACYL COA to 1-acyl-sn-glycerol 3-phosphate to generate 1,2-diacyl-sn-glycerol 3-phosphate. This enzyme has alpha, beta, gamma, delta and epsilon subunits.Acro-Osteolysis: A condition with congenital and acquired forms causing recurrent ulcers in the fingers and toes. The congenital form exhibits autosomal dominant inheritance; the acquired form is found in workers who handle VINYL CHLORIDE. When acro-osteolysis is accompanied by generalized OSTEOPOROSIS and skull deformations, it is called HAJDU-CHENEY SYNDROME.Antiretroviral Therapy, Highly Active: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Progeria: An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Complement C3 Nephritic Factor: An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.Body Fat Distribution: Deposits of ADIPOSE TISSUE throughout the body. The pattern of fat deposits in the body regions is an indicator of health status. Excess ABDOMINAL FAT increases health risks more than excess fat around the hips or thighs, therefore, WAIST-HIP RATIO is often used to determine health risks.Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.Hypertriglyceridemia: A condition of elevated levels of TRIGLYCERIDES in the blood.Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules.Body Composition: The relative amounts of various components in the body, such as percentage of body fat.Muscular Dystrophy, Emery-Dreifuss: A heterogenous group of inherited muscular dystrophy without the involvement of nervous system. The disease is characterized by MUSCULAR ATROPHY; MUSCLE WEAKNESS; CONTRACTURE of the elbows; ACHILLES TENDON; and posterior cervical muscles; with or without cardiac features. There are several INHERITANCE PATTERNS including X-linked (X CHROMOSOME), autosomal dominant, and autosomal recessive gene mutations.HIV Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Contracture: Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint.Phosphatidate Phosphatase: A phosphomonoesterase involved in the synthesis of triacylglycerols. It catalyzes the hydrolysis of phosphatidates with the formation of diacylglycerols and orthophosphate. EC 3.1.3.4.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.PPAR gamma: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Adipogenesis: The differentiation of pre-adipocytes into mature ADIPOCYTES.Oman: A sultanate on the southeast coast of the Arabian peninsula. Its capital is Masqat. Before the 16th century it was ruled by independent emirs but was captured and controlled by the Portuguese 1508-1648. In 1741 it was recovered by a descendent of Yemen's imam. After its decline in the 19th century, it became virtually a political and economic dependency within the British Government of India, retaining close ties with Great Britain by treaty from 1939 to 1970 when it achieved autonomy. The name was recorded by Pliny in the 1st century A.D. as Omana, said to be derived from the founder of the state, Oman ben Ibrahim al-Khalil. (From Webster's New Geographical Dictionary, 1988, p890; Oman Embassy, Washington; Room, Brewer's Dictionary of Names, 1992, p391)Subcutaneous Fat: Fatty tissue under the SKIN through out the body.Oligomenorrhea: Abnormally infrequent menstruation.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Cocos: A plant genus of the family ARECACEAE. It is a tropical palm tree that yields a large, edible hard-shelled fruit from which oil and fiber are also obtained.Subcutaneous Tissue: Loose connective tissue lying under the DERMIS, which binds SKIN loosely to subjacent tissues. It may contain a pad of ADIPOCYTES, which vary in number according to the area of the body and vary in size according to the nutritional state.

*  Hyperlipid: PCOS and LC; is pregnancy a side effect?

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Hyperlipid: Proto-Ech

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Hyperlipid: Gluten Dr Briffa link

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Hyperlipid: Living on the isolated island of Kitava

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Hyperlipid: Starvation and cancer growth: Sauer vs Lisanti

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Hyperlipid: Fructose and metabolic syndrome: Uric acid

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Hyperlipid: Acetoacetate and arterial oxygen tension

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ... Some venous blood gets through and lowers the oxygen partial pressure in arterial blood. Higher oxygen partial pressure in ... Low O2 takes over as partial pressure drops as you climb. The same applies to swimming under water as John U comments. I have ... Aside: pO2 here is the partial pressure of oxygen in the arterial blood. This is only linked to oxygen content via the the ...

*  Hyperlipid: Lipoprotein(a), a prickly subject

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  The Human Lipodystrophy Gene BSCL2/Seipin May Be Essential for Normal Adipocyte Differentiation | Diabetes

... implications for Dunnigan-type familial partial lipodystrophy. Hum Mol Genet15 :653 -663,2006. ... Loss of AGPAT2 activity causes lipodystrophy in humans (BSCL type 1), and lipin 1 disruption causes lipodystrophy in the fld ... Peterfy M, Phan J, Xu P, Reue K: Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein ... Szymanski KM, Binns D, Bartz R, Grishin NV, Li WP, Agarwal AK, Garg A, Anderson RG, Goodman JM: The lipodystrophy protein ...

*  Hyperlipid: Fructose and Gout

Dunnigan Familial Partial Lipodystrophy (1) * Earning a crust (1) * Easiyo (1) * Eat as much starch as you wish (1) ...

*  Cellular Basis of Laminopathies

2003) Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered ...

*  Akcea Therapeutics Inc (AKCA) Stock Message Board - InvestorsHub

... and is currently in Phase III clinical development for the treatment of familial partial lipodystrophy (FPL). The Company's ... Ionis). The Company's volanesorsen drug has completed a Phase III clinical program for the treatment of familial ...

*  Acanthosis Nigricans

https://ghr.nlm.nih.gov/condition/familial-partial-lipodystrophy. https://ghr.nlm.nih.gov/condition/congenital-generalized- ... lipodystrophy. https://ghr.nlm.nih.gov/condition/rabson-mendenhall-syndrome. https://ghr.nlm.nih.gov/condition/donohue-syndrome ...

*  Peptides and Proteins: Novus Biologicals

Familial Generalized Lipodystrophy (5). *. Familial Hemophagocytic Lymphocytosis (1). *. Familial Partial Lipodystrophy (3) ...

*  Novelion Therapeutics Reports Preliminary 2016 Net Product Sales and Provides 2017 Outlook | Novelion

LIMITATIONS OF USE: The safety and effectiveness of MYALEPT for the treatment of complications of partial lipodystrophy or for ... with an identified population of more than 160 patients with homozygous familial hypercholesterolemia (HoFH) and favorable ... and in a subset of patients with partial lipodystrophy (PL). As with GL patients, in the pivotal NIH study, the subset of PL ... T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with ...

*  Paget's, of bone disease | definition of Paget's, of bone disease by Medical dictionary

Barraquer's disease partial lipodystrophy.. Basedow's disease Graves' d.. Batten disease , Batten-Mayou disease 1. Vogt- ... disease, familial,. n a disease occurring in several members of the same family. Often used to mean members of the same ... Hailey-Hailey disease benign familial pemphigus.. Hallervorden-Spatz disease an autosomal recessive disorder caused by ... Gm2 gangliosidosis type 1; infantile amaurotic familial idiocy. See Niemann-Pick disease.. Terrien's disease See corneal ...

LipodystrophyHIV-associated lipodystrophy: HIV-associated lipodystrophy is a condition characterized by loss of subcutaneous fat associated with infection with HIV.Familial partial lipodystrophy: Familial partial lipodystrophy (also known as "Köbberling–Dunnigan syndrome") is an autosomal dominant skin condition characterized by the loss of subcutaneous fat.Diabetes (disambiguation): Diabetes usually refers to a group of metabolic diseases in which a person has high blood sugar.Methylsterol monooxygenase: Methylsterol monooxygenase (, methylsterol hydroxylase, 4-methylsterol oxidase, 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol,hydrogen-donor:oxygen oxidoreductase (hydroxylating)) is an enzyme with system name 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol,NAD(P)H:oxygen oxidoreductase (hydroxylating). This enzyme catalyses the following chemical reactionAcanthosis nigricansGlycerol-3-phosphate 2-O-acyltransferase: Glycerol-3-phosphate 2-O-acyltransferase (, sn-2-glycerol-3-phosphate O-acyltransferase, glycerol-3-phosphate O-acyltransferase) is an enzyme with system name acyl-CoA:sn-glycerol 3-phosphate 2-O-acyltransferase. This enzyme catalyses the following chemical reactionMandibuloacral dysplasia: Mandibuloacral dysplasia is a rare autosomal recessive syndrome characterized by mandibular hypoplasia, delayed cranial suture closure, dysplastic clavicles, abbreviated and club-shaped terminal phalanges, acroosteolysis, atrophy of the skin of the hands and feet, and typical facial changes.James, William; Berger, Timothy; Elston, Dirk (2005).Adipose tissue macrophages: Adipose tissue macrophages (abbr. ATMs) comprise tissue resident macrophages present in adipose tissue.StavudineManagement of HIV/AIDS: The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs in an attempt to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle.Progeroid syndromes: Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term progeroid syndrome does not necessarily imply progeria (Hutchinson-Gilford progeria syndrome), which is a specific type of progeroid syndrome.Lamin: Nuclear lamins, also known as Class V intermediate filaments, are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope.LeptinHypertriglyceridemiaSubcutaneous T-cell lymphoma: Subcutaneous T-cell lymphoma (also known as a "Panniculitis-like T-cell lymphoma") is a cutaneous condition that most commonly presents in young adults, and is characterized by subcutaneous nodules.Emerin: Emerin is a protein that in humans is encoded by the EMD gene, also known as the STA gene. Emerin, together with MAN1, is a LEM domain-containing integral protein of the inner nuclear membrane in vertebrates.Protease inhibitor (pharmacology): Protease inhibitors (PIs) are a class of antiviral drugs that are widely used to treat HIV/AIDS and hepatitis caused by hepatitis C virus. Protease inhibitors prevent viral replication by selectively binding to viral proteases (e.Congenital contractural arachnodactyly: Beals syndrome (congenital contractural arachnodactyly, Beals-Hecht syndrome) is a rare congenital connective tissue disorder. Beals syndrome has only recently been described as a syndrome distinct from Marfan's syndrome.Conference on Retroviruses and Opportunistic Infections: The Conference on Retroviruses and Opportunistic Infections (CROI) is an annual scientific meeting devoted to the understanding, prevention and treatment of HIV/AIDS and the opportunistic infections associated with AIDS. Thousands of leading researchers and clinicians from around the world convene in a different location in North America each year for the Conference.Adipogenesis: Adipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. Adipogenesis has been one of the most intensively studied models of cellular differentiation.Energy in Oman: Energy in Oman describes energy and electricity production, consumption and import in Oman. Energy policy of Oman will describe the energy policy in the politics of Oman more in detail.OligomenorrheaLipotoxicity: Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle.Pedigree chart: A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next,pedigree chart Genealogy Glossary - About.com, a part of The New York Times Company.Demographics of the Cocos (Keeling) Islands: This article is about the demographic features of the population of the Cocos (Keeling) Islands, including population density, ethnicity, education level, health of the populace, economic status, religious affiliations and other aspects of the population.Subcutaneous tissue

(1/27) Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism.

The lipodystrophies are characterized by loss of adipose tissue in some anatomical sites, frequently with fat accumulation in nonatrophic depots and ectopic sites such as liver and muscle. Molecularly characterized forms include Dunnigan-type familial partial lipodystrophy (FPLD), partial lipodystrophy with mandibuloacral dysplasia (MAD), Berardinelli-Seip congenital generalized lipodystrophy (CGL), and some cases with Barraquer-Simons acquired partial lipodystrophy (APL). The associated mutant gene products include 1) nuclear lamin A in FPLD type 2 and MAD type A; 2) nuclear lamin B2 in APL; 3) nuclear hormone receptor peroxisome proliferator-activated receptor gamma in FPLD type 3; 4) lipid biosynthetic enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 in CGL type 1; 5) integral endoplasmic reticulum membrane protein seipin in CGL type 2; and 6) metalloproteinase ZMPSTE24 in MAD type B. An unresolved question is whether metabolic disturbances are secondary to adipose repartitioning or result from a direct effect of the mutant gene product. Careful analysis of clinical, biochemical, and imaging phenotypes, using an approach called "phenomics," reveals differences between genetically stratified subtypes that can be used to guide basic experiments and to improve our understanding of common clinical entities, such as metabolic syndrome or the partial lipodystrophy syndrome associated with human immunodeficiency virus infection.  (+info)

(2/27) Long-term efficacy of leptin replacement in patients with Dunnigan-type familial partial lipodystrophy.

The Dunnigan-type familial partial lipodystrophy (FPLD) is characterized by a variable loss of fat from the extremities and trunk and excess subcutaneous fat in the chin and supraclavicular area. Associated metabolic abnormalities include hypoleptinemia, insulin resistance, and dyslipidemia. Our goal was to observe changes in metabolic parameters for patients with FPLD on long-term leptin replacement and to compare the metabolic characteristics seen in FPLD with those seen in generalized lipodystrophy (GL) from our previous studies. This was an open-label study of 6 patients with FPLD receiving maximal doses of oral antidiabetic and lipid-lowering medications at baseline. Recombinant leptin was given through twice-daily subcutaneous injections at a maximal dose of 0.08 mg/kg per day over 12 months to simulate normal to high normal physiologic levels. Triglycerides were reduced by 65% at 4 months (749+/-331 to 260+/-58 mg/dL) and significantly reduced at 12 months for 5 patients (433+/-125 to 247+/-69 mg/dL; P=.03). Total cholesterol also decreased (280+/-49 to 231+/-41 mg/dL; P=.01). Insulin sensitivity and fasting glucose levels (190+/-26 to 151+/-15 mg/dL; P<.01) improved. Glucose tolerance and glycosylated hemoglobin levels (8.4%+/-0.6% to 8.0%+/-0.4%; P=.07) did not change. As shown in patients with GL, patients with FPLD have improvement in triglycerides, fasting glucose, and insulin sensitivity with leptin replacement. In contrast to the patients with GL, the patients with FPLD are older, have higher leptin levels, and notably lower insulin secretion for a similar degree of hyperglycemia. Low-dose recombinant methionyl human leptin for patients with FPLD has an important role in improving triglycerides, beyond that of available lipid-lowering agents. In improving glycemic control, normalization of glucose tolerance in hypoinsulinemic patients with FPLD requires insulin and leptin therapy. This is the first study to examine the effects of long-term leptin replacement in patients with FPLD.  (+info)

(3/27) A pathogenic mechanism leading to partial lipodistrophy and prospects for pharmacological treatment of insulin resistance syndrome.

The understanding of a common complex phenotype such as insulin resistance can be favoured by evaluation of monogenic syndromes. Clinical definition, pathogenesis, and therapeutical strategies for the insulin resistance syndrome can thus be improved by the characterization at the molecular genetic level of monogenic forms of lipodystrophies. Here we report experimental evidence on the pathogenic mechanism underlying insulin resistance in a rare form of laminopathy, due to mutation of the LMNA gene coding for lamin A/C, the Dunnigan-type familial partial lipodystrophy (FPLD). The defect, consisting in the intranuclear accumulation of mutant unprocessed precursors of lamin A, reduces the amount of the DNA-bound adipocyte transcription factor sterol regulatory element binding protein 1 (SREBP1) and lowers the peroxisome proliferator-activated receptor (PPARgamma) expression, causing the impairment of pre-adipocyte differentiation. The treatment with the PPARgamma ligand troglitazone (TDZ) is able to rescue the adipogenic program. Since FPLD recapitulates the essential metabolic abnormalities of the common insulin resistance syndrome, the beneficial effects of TDZ on monogenic lipodystrophies might provide a clue as to the future treatment strategies also for the common syndrome of insulin resistance.  (+info)

(4/27) The retinol acid receptor B gene is hypermethylated in patients with familial partial lipodystrophy.

Mutations in the LMNA gene cause various phenotypes including partial lipodystrophy, muscular dystrophies, and progeroid syndromes. The specific mutation position within the LMNA sequence can partially predict the phenotype, but the underlying mechanisms for the development of these different phenotypes are still unclear. To investigate whether different DNA methylation patterns contribute to the development of different phenotypes caused by LMNA mutations, we analyzed a panel of ten candidate genes related to fat metabolism, aging, and a tendency to different methylation patterns: CSPG2, ESR1, IGF1R, IGFR2, LMNA, MLH1, RANBP1, RARB, ZMPSTE24, and TGFBR1. We studied two independent families each comprising three individuals affected by familial partial lipodistrophy type 2 (FPLD2). Affected members in each family carried two different mutations of the LMNA gene (R482L and R471G respectively). In addition, we analyzed four progeria patients (2xLMNA/C G608G, 1xLMNA/C S143F, and 1xZMPSTE24 IVS9-Ex10) and seven healthy adults. The gene encoding retinoic acid receptor B (RARB) showed a higher methylation in all six patients with FPLD2 when compared with the progeria patients with other LMNA mutations as well as the healthy controls (P<0.05). All other investigated genes showed no difference in the methylation patterns between the groups. A drug-induced inhibition of the retinol pathway is discussed as the key pathway for developing HAART-associated lipodystrophy and our data support a possible role of the retinol pathway in the development of lipodystrophy phenotypes.  (+info)

(5/27) Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence.

Lipodystrophic syndromes associated with mutations in LMNA, encoding A-type lamins, and with HIV antiretroviral treatments share several clinical characteristics. Nuclear alterations and prelamin A accumulation have been reported in fibroblasts from patients with LMNA mutations and adipocytes exposed to protease inhibitors (PI). As genetically altered lamin A maturation also results in premature ageing syndromes with lipodystrophy, we studied prelamin A expression and senescence markers in cultured human fibroblasts bearing six different LMNA mutations or treated with PIs. As compared to control cells, fibroblasts with LMNA mutations or treated with PIs had nuclear shape abnormalities and reduced proliferative activity that worsened with increasing cellular passages. They exhibited prelamin A accumulation, increased oxidative stress, decreased expression of mitochondrial respiratory chain proteins and premature cellular senescence. Inhibition of prelamin A farnesylation prevented cellular senescence and oxidative stress. Adipose tissue samples from patients with LMNA mutations or treated with PIs also showed retention of prelamin A, overexpression of the cell cycle checkpoint inhibitor p16 and altered mitochondrial markers. Thus, both LMNA mutations and PI treatment result in accumulation of farnesylated prelamin A and oxidative stress that trigger premature cellular senescence. These alterations could participate in the pathophysiology of lipodystrophic syndromes and lead to premature ageing complications.  (+info)

(6/27) New PPARG mutation leads to lipodystrophy and loss of protein function that is partially restored by a synthetic ligand.

PURPOSE: Familial partial lipodystrophy caused by mutations in the PPARG gene is characterised by altered distribution of subcutaneous fat, muscular hypertrophy and symptoms of metabolic syndrome. PPARG encodes peroxisome proliferator-activated receptor (PPAR)gamma, a nuclear hormone receptor playing a crucial role in lipid and glucose metabolism and in several other cellular regulatory processes. METHODS: PPARG was screened for mutations by direct sequencing in two patients with lipodystrophy, one unaffected family member and 124 controls. Body composition was examined in affected patients, and they were investigated for abnormalities in laboratory results. Functional analysis of the mutant protein was assessed by determining transcriptional activity and possible interference with the wild-type protein. RESULTS: In two patients with familial partial lipodystrophy, we identified a nucleotide substitution in the PPARG gene. This mutation results in the substitution of aspartate by asparagine at residue 424 (D424N) in the ligand-binding domain of PPARgamma. The unaffected family member and all 124 controls did not carry this mutation. D424N PPARgamma had a significantly lower ability than wild-type PPARgamma to activate a PPARgamma-stimulated reporter gene, but did not exert a negative effect on the wild-type protein. Partial activation of D424N PPARgamma was achieved in the presence of the agonist rosiglitazone. CONCLUSION: We report a new PPARG mutation, D424N, which is located in the ligand-binding domain of the protein and leads to familial partial lipodystrophy. D424N PPARgamma exhibited a loss of function, which was partially restored by adding the PPARgamma agonist rosiglitazone, suggesting possible treatment potential of this agent.  (+info)

(7/27) Efficacy of pioglitazone in familial partial lipodystrophy of the Dunnigan type: a case report.

A 25 year old woman consulted for a severe acanthosis nigricans and central distribution of fat. Her masculine type morphology was associated with muscular appearance of the limbs and excess fat deposits in the face and neck. Biological testing confirmed glucose intolerance associated with a severe insulin resistance, hypertriglyceridemia and polycystic ovary syndrome. The detection of a heterozygous missense mutation in LAMIN A/C gene at position 482 confirmed the diagnosis of Familial Partial Lipodystrophy (FPLD2). Due to a deterioration of clinical and metabolic status, 15 and then 30 mg per day of pioglitazone were added to her previous treatment with metformin, bezafibrate and omega-3 fatty acids. Metabolic status improved rapidly after 3 months and continued thereafter. Weight remained stable, body mass composition and waist circumference improved. After 18 months of treatment, glycaemia and triglycerides levels normalized, hepatic enzymes and liver echographic features improved. Insulin sensitivity improved dramatically with a HOMA % S value of 73% with metformin and of 98.2% when pioglitazone was added. Leptin levels increased from 6.6 to 10.2 microg/ml. We report a very rapid and good efficacy of pioglitazone added to metformin without side effects in FPLD2. If confirmed on more patients, early use of pioglitazone in association with metformin could be proposed in FPLD2.  (+info)

(8/27) Resistance to high-fat diet-induced obesity but exacerbated insulin resistance in mice overexpressing preadipocyte factor-1 (Pref-1): a new model of partial lipodystrophy.

 (+info)



congenital

  • OBJECTIVE- Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tissue. (diabetesjournals.org)