Search

Homozygosity mapping results for two pedigrees from Portugal and Mexico with an autosomal-recessive auto-inflammatory syndrome characterized by joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) are presented. The study results suggested that mutations in PSMB8 cause JMP syndrome, most possibly by affecting MHC class I antigen processing.

Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-[kappa]B signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance. diabetes | insulin resistance | obesity www.pnas.org/cgi/doi/10.1073/pnas.0905310107

ABSTRACT Demand for facial volume augmentation procedures is increasing, along with a growing appreciation for the importance of objective, quantitative measures of treatment success. This article reviews currently available three-dimensional [...]

Central fat accumulation is increasingly recognized as a problem for patients with HIV infection. The term 'lipodystrophy' has been used to describe collectively a constellation of body habitus changes and metabolic abnormalities commonly observed in HIV-infected patients, particularly since the advent of highly active antiretroviral therapy. Visceral fat accumulation can place patients at increased risk of coronary artery disease. Furthermore, body shape changes are a source of distress to patients that may compromise treatment adherence. Reduction of abdominal obesity can therefore be considered part of therapy in HIV-positive patients with visceral adipose tissue (VAT) accumulation. Currently, there are no drugs approved by the Food and Drug Administration for the treatment of HIV-associated central fat accumulation. Lifestyle modifications such as diet and exercise and switching antiretroviral therapies appear to be of limited value in reducing VAT. Metformin has shown some benefit in reducing VAT but at the expense of accelerating peripheral fat loss, and the thiazolidinediones have no effect on VAT. Similarly, testosterone does not appear to reduce VAT in these patients, and there are no data on anabolic steroids. Two large, randomized controlled trials have demonstrated the efficacy of recombinant human growth hormone (rhGH) in reducing visceral adipose tissue. There are also promising data regarding treatment with growth hormone releasing hormone (GHRH).

The diagnosis, treatment and management of a 39-year-old male manifesting HIV-associated lipodystrophy are discussed.

In this cross-sectional study, we sought to determine whether gene expression of macrophage markers and inflammatory chemokines in lipoatrophic subcutaneous abdominal adipose tissue and liver fat content are increased and interrelated in human immunodeficiency virus (HIV)1-positive, highly active antiretroviral therapy (HAART)-treated patients with lipodystrophy (HAART+LD+; n = 27) compared with those without (HAART+LD-; n = 13). The study groups were comparable with respect to age, gender, and body mass index. The HAART+LD+ group had twofold more intra-abdominal (P = 0.01) and 1.5-fold less subcutaneous (P = 0.091) fat than the HAART+LD- group. As we have reported previously, liver fat was 10-fold higher in the HAART+LD+ compared with the HAART+LD- group (P = 0.00003). Inflammatory gene expression was increased in HAART-lipodystrophy: CD68 4.5-fold (P = 0.000013), tumor necrosis factor (TNF)-[alpha] 2-fold (P = 0.0094), chemokine (C-C motif) ligand (CCL) 2 2.5-fold (P = 0.0024), CCL3 7-fold (P = 0.0000017), integrin [alpha]M (ITGAM) 3-fold (P = 0.00067), epidermal growth factor-like module containing, mucin-like, hormone receptor-like (EMR)1 2.5-fold (P = 0.0038), and a disintegrin and metalloproteinase domain (ADAM)8 3.5-fold (P = 0.00057) higher in the HAART+LD+ compared with the HAART+LD- group. mRNA concentration of CD68 (r = 0.37, P = 0.019), ITGAM (r = 0.35, P = 0.025), CCL2 (r = 0.39, P = 0.012), and CCL3 (r = 0.54, P = 0.0003) correlated with liver fat content. In conclusion, gene expression of markers of macrophage infiltration and adipose tissue inflammation is increased in lipoatrophic subcutaneous abdominal adipose tissue of patients with HAART-associated lipodystrophy compared with those without. CD68, ITGAM, CCL2, and CCL3 expression is significantly associated with accumulation of liver fat. human immunodeficiency virus; macrophages; cytokines

Lipodystrophy is one of the foremost concerns among the HIV-positive population, and is often associated with psychosocial disorders. We evaluated the clinical efficacy of facial infiltrations with autologous fat, polylactic acid, and polyacrylamide gel using clinical inspection and facial photographs (ordinal scale). Additionally, we assessed the safety of the infiltration techniques and determined changes in patient satisfaction, emotional status, and quality of life. Evaluations were made at 48- and 96-week follow-up visits. This paper presents the 48-week follow-up results. The current analysis includes 138 patients: 8, 25, and 105 in the fat, polylactic acid, and polyacrylamide gel groups, respectively. At baseline, almost 50% of the patients (67/138) presented grades 3 and 4 lipoatrophy, but at week 48 only 7.5% (7/93) remained in these advanced grades (no patients from the polyacrylamide group). A new round of infiltrations at week 48 was necessary in 35% (33/93) of patients (88%, 84%, and 8% in the fat, polylactic, and polyacrylamide groups, respectively). No serious adverse events were detected with any of the substances. Patient satisfaction and quality of life improved significantly in all three groups. Infiltrations with autologous fat, polylactic acid, or polyacrylamide gel appear to be an effective and safe alternative to repair facial lipoatrophy, at least up to 48 weeks, significantly improving patient quality of life. Similar results were observed for all degrees of severity and between genders. Polyacrylamide gel provided the longest lasting benefits.

Lipoatrophy (LA) is a form of lipodystrophy, characterized by volume depletion caused by fat loss in the limbs, buttocks, and face. Facial volume loss is the most obvious outward sign of LA because it alters the facial contours in the cheeks, temples, and orbits. Lipodystrophy and LA are most commonly seen in patients with HIV on highly active antiretroviral therapy (HAART), which was introduced in the mid-1990s for the management of HIV, and is currently considered the mainstay therapy for HIV-infected patients. However, the etiology of LA is likely multifactorial as underlying patient conditions, including duration and severity of HIV and increasing age, have also been found to contribute to its occurrence. The volume loss of LA can be very dramatic with some patients exhibiting no signs of facial fat. As a result, many HIV-infected patients with associated LA suffer from psychological and lifestyle effects, which can lead to noncompliance with HAART. Thus, increases in facial volume and improvement in morphology is anticipated to reduce anxiety caused by LA in HIV-infected patients, and improve quality of life. This review discusses the benefits and limitations of several treatment options available to correct the volume depletion associated with LA, including antiretroviral switching, permanent surgical implants and injectables, poly-L-lactic acid, collagen, and hyaluronic acid derivatives.

Prior HIV lipodystrophy (LD) scales have been unidimensional, often combining changes of fat loss with fat accumulation with retinoid changes. Our objective was to determine the psychometric properties of a LD scale used in an outpatient LD subspecialty clinic at a university hospital HIV clinic. A patient and clinician self-administered LD scale was used to evaluate 107 patients referred to the Owen LD Clinic from March of 1999 to August of 2002. Sixteen measures of the LD syndrome were assessed on a severity scale ranging from 0 (none) to 3 (severe). SPSS was used to perform a reliability and factor analysis. A total of 150 paired patient and clinician assessments were performed. Thirty-one patients had repeat assessments. Reliability analysis of the patient and clinician self-administered LD scale revealed an alpha of 0.76 and 0.73, respectively. Factor analysis of patient self-assessment of LD identified 3 factors, which clustered in the following order: fat loss, fat accumulation, and retinoid changes. Factor analysis of clinician self-assessment of LD identified 4 factors. The first factor clustered around items of fat loss. A second cluster consisted of retinoid changes. The final 2 factors clustered around items consistent with fat accumulation. The patient and clinician self-administered Owen Clinic LD scale was found to be highly reliable and useful in the assessment of LD. Our analysis confirms clinical intuition that the evaluation of LD is a multidimensional construct and that 3 subscales may be used to evaluate dimensions of fat loss, fat accumulation, and retinoid changes.

Research has been conducted on relationship between leptin and adiponectin serum levels in patients with HIV-associated lipodystrophy. Results suggest that adiponectin deficiency in people with HIV-associated lipodystrophy may be responsible for reduced insulin sensitivity.

Byline: H. H. Hirsch (1), M. Battegay (1) Abstract: Progressive changes in the distributions of body fat and severe alterations of lipid, glucose and lactate levels challenge the mid and long-term success of highly active antiretroviral therapy of HIV-infection. Both clinical diagnosis of the lipodystrophy syndrome and scientific elucidation of the underlying mechanisms may benefit from a working case definition. In this article, pathophysiological and therapeutic aspects are discussed with reference to physical and metaboloic changes. Checkpoints for a practical approach to the patient at risk are given. Specific care and management depend on th epredominant alteration, the stage of HIV disease and the medical and antiretroviral history of the individual patient. Author Affiliation: (1) Division of Infectious Diseases, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. mbattegay@uhbs.ch, CH Article note: Received: February 26, 2002 * Revision accepted: May 14, 2002 M. Battegay (corresponding author)

Leptin replacement therapy appears to be beneficial in patients with lipodystrophy, according to a study of nine patients. Lipodystrophy is characterized by a destruction of fat cells, which produce the hormone leptin. This causes low leptin levels, which increases the risk of insulin resistance, obesity, and diabetes.

ABSTRACT Background: Facial lipoatrophy is a common problem for patients with human immunodeficiency virus (HIV) treated with highly active antiretroviral therapy (HAART). The loss of subcutaneous facial tissue occurs in [...]