Disease relevance of Lipodystrophy

• Despite this lipodystrophy, Crebbp+/- mice showed increased insulin sensitivity and glucose tolerance and were completely protected from body weight gain induced by a high-fat (HF) diet [1].
• Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial [2].
• The duration of indinavir use may represent an additional contribution for the development of lipodystrophy with central obesity (1.26 per 6 months extra [0.99-1.60]); p=0.064) [3].
• It has been proposed that some of these adverse effects (including myopathy, cardiomyopathy, anaemia, hyperlactataemia/ lactic acidosis, pancreatitis, polyneuritis and lipodystrophy) could be mediated by mitochondrial (mt) toxicity [4].
• Factors associated with development of hypertension were: male sex, higher BMI, older age, higher BP at baseline, high total cholesterol and clinical lipodystrophy [5].

Psychiatry related information on Lipodystrophy

• MT was not associated with gender, age, alcohol consumption, type of IFN, degree of steatosis and fibrosis in liver biopsy, presence of lipodystrophy, CD4+ cell count, HCV or HIV viral load, mitochondrial DNA and COXII-expression in liver tissue, or antiretroviral therapy containing d4T or protease inhibitors [6].

High impact information on Lipodystrophy

• Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice [1].
• Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin [7].
• Our results indicate that lipin is required for normal adipose tissue development, and provide a candidate gene for human lipodystrophy [7].
• LMNA, encoding lamin A/C, is mutated in partial lipodystrophy [8].
• Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase [8].

Chemical compound and disease context of Lipodystrophy

• However, of the 21 patients with partial lipodystrophy, 17 had low serum C3, with normal C4 and C2, concentrations, accompanied in 14 by a serum C3 splitting factor indistinguishable from nephritic factor, suggesting activation of the alternative pathway [9].
• MAIN OUTCOME MEASURES: The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels [10].
• Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict lipodystrophy severity [11].
• Treatment of lipodystrophy with troglitazone [12].
• The finding of relative preservation of fat associated with gemfibrozil therapy deserves further investigation in the search of potential effective therapies for lipodystrophy in HIV-infected subjects [13].

Biological context of Lipodystrophy

• However, a new mouse model that expresses the analog of a human PPARG mutation displays minimal lipodystrophy and insulin resistance but rather severe hypertension [14].
• Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice [15].
• TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy [16].
• Drug interaction of isotretinoin and protease inhibitors: support for the cellular retinoic acid-binding protein-1 theory of lipodystrophy [17]?
• The lipodystrophy mutation R482Q, which causes a different phenotype and is believed to act through an emerin-independent mechanism, was indistinguishable from wild-type in its localization and its ability to trap emerin at the nuclear rim [18].

Anatomical context of Lipodystrophy

• We analyzed the VDR of a patient who exhibited three genetic diseases: HVDRR, congenital total lipodystrophy, and persistent mullerian duct syndrome [19].
• Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy [20].
• Role of CD95-mediated adipocyte loss in autoimmune lipodystrophy [21].
• Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes [22].
• Mutations in emerin and nuclear lamins have been associated with muscular dystrophies and lipodystrophy, raising new questions about the functions of inner nuclear membrane proteins [23].

Gene context of Lipodystrophy

• Site and mechanism of leptin action in a rodent form of congenital lipodystrophy [24].
• We now show compound heterozygous mutations, Phe361fsX379 and Trp340Arg, in the zinc metalloproteinase (ZMPSTE24) gene in one of the four patients who had severe MAD associated with progeroid appearance and generalized lipodystrophy [25].
• Prevalence of mutations in AGPAT2 among human lipodystrophies [26].
• The germline transmission of a transactivation-deficient mutation in PPARG suggests that autosomal dominant partial lipodystrophy is genetically heterogeneous [27].
• OBJECTIVES: To examine whether ARV therapy might inhibit the expression of CD36, which is known to play an important role in fatty acid and glucose metabolism, and if this might contribute to the metabolic alterations associated with lipodystrophy [28].

Analytical, diagnostic and therapeutic context of Lipodystrophy

• Triglyceride increase can predict lipodystrophy in HIV patients under highly active antiretroviral therapy [29].
• In multivariate analysis, lipodystrophy was associated with older age (per year) (AOR 1.03; 95% CI 1.01, 1.04), the use of ingested alternative therapies (AOR 1.46; 95% CI 1.06, 2.01), having ever used protease inhibitors (PI) (AOR 2.63; 95% CI 1.89, 3.66), and duration of stavudine treatment (per year) (AOR 1.35; 95% CI 1.15, 1.58) [30].
• The effect of fenfluramine and caloric restriction on carbohydrate homeostasis in patients with lipodystrophy [31].
• To investigate the association of adiponectin with metabolic changes in human lipodystrophy, we conducted a cross-sectional study of 112 HIV-infected patients treated with HAART [32].
• Lower levels of high-density lipoprotein cholesterol, higher body-mass index, and lipodystrophy are potentially modifiable risk factors associated with the severity of steatosis [33].

References