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PubMed2001

Peroxisomal proliferator-activated ligand therapy for HIV lipodystrophy.

Lipodystrophies associated with HIV disease have been reported in recent years and have included a general redistribution of fat with more central fat and increased dorsocervical fat. These lipodystrophies are commonly associated with hyperlipidemia and in some cases with insulin resistant diabetes. Although a similar redistribution of fat is seen in hypercortisolism, in general, serum and urinary cortisol levels are normal in these HIV-positive patients. However cortisol/dehydroepaindrosterone (DHEA) ratios are increased in HIV disease and may result in a relative hypercortisolism. Seven HIV-positive male patients on multidrug antiviral therapy including HIV protease inhibitors had developed increased central and dorsocervical fat over 1 year. All patients had increased serum lipids and three had insulin resistant diabetes. Four patients were treated initially with DHEA 100-200 mg/day, with addition of a cyclo-oxygenase (COX) inhibitor (indomethacin 100 mg/day) and three others were treated from the onset with a combination of DHEA 200 mg/day and a COX inhibitor (indomethacin 100 mg/day or naprosyn 1000 mg/day). All patients reported moderation or normalization of their serum lipids and some moderation of blood sugars while on DHEA alone. More marked improvement in blood sugar and noticeable decreases in the dorsocervical fat; however, occurred only with addition a COX inhibitor. Both DHEA and COX inhibitors have a number of mechanisms of action; among these is their role as a peroxisome proliferator-activator receptor ligand. Dysregulation of peroxisome function is associated with the spectrum of biochemical changes seen within these HIV associated lipodystrophies. Use of HIV protease inhibitors is reported in the majority of patients with these lipodystrophies, and protease inhibitors may accentuate the underlying peroxisome dysregulation. Supplementation with DHEA and a COX inhibitor may improve peroxisomal function.

Anti-HIV Agents↗

PubMed2002

LDL-receptors expression in HIV-infected patients: relations to antiretroviral therapy, hormonal status, and presence of lipodystrophy.

BACKGROUND: Abnormalities in lipid levels and lipodystrophy (LD) have been commonly reported after commencement of highly active antiretroviral therapy (HAART). A major mechanism by which plasma low-density lipoprotein (LDL) cholesterol levels may be influenced is via the regulation of hepatic LDL receptor expression. The activity of LDL receptors is under hormonal control. Moreover, HIV infection and HAART are associated with important modifications of hormonal status. As the cause of these adverse reactions is unknown, the effects of HAART and lipodystrophy on LDL receptors were evaluated. MATERIALS AND METHODS: Thirty-nine HIV treated patients (21 with a protease inhibitor (PI) containing regimen, 18 without PI use) and 22 control subjects were tested for insulin resistance (HOMA model assessment), lipid profile, serum concentration of dehydroepiandrosterone (DHEA) and LDL-R expression. LDL-R on mononuclear cells were quantified by flow cytrometry. RESULTS: Among the 39 HIV infected patients, 14 patients had a lipodystrophy (LD). Patients with LD had significantly higher levels of triglyceride (TG) and insulin resistance compared to patients without LD. There was no significant difference in LDL-R count between patients with or without PI use. In contrast, LDL-R count was significantly lower in patients with LD compared with those without (8504 +/- 3901 vs. 13 200 +/- 4532, P = 0.001). There was no difference in LDL-R count between patients without LD and control subjects. Patients with LD had lower levels of DHEA compared to patients without LD. In HIV-infected patients, we found a significant correlation between LDL-R expression and TG (r = -0.32; P = 0.04) and LDL cholesterol (r = -0.33; P = 0.04). In contrast, we did not observe a correlation between DHEA level and LDL-R count or LDL cholesterol level. CONCLUSIONS: HIV-lipodystrophy is associated with a lower expression of LDL-R. This decreased expression of LDL-R seems independent of DHEA or insulin secretion.

Adult↗

PubMed2002

Does race protect an oriental population from developing lipodystrophy in HIV-infected individuals on HAART?

OBJECTIVES: Lipodystrophy, hyperlipidaemia and hyperinsulinaemia are common metabolic complications of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected Caucasians. We questioned whether such complications also occur in other races. METHODS: A cross-sectional analysis was performed in an outpatient clinic of a university teaching hospital with 156 Koreans, divided into HIV-infected subjects receiving HAART (n=57, group 1), HAART-naïve subjects (n=42, group 2), and healthy controls (n=57, group 3). Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, total cholesterol, low-density (LDL) and high-density lipoprotein (HDL) cholesterol, free fatty acid (FFA), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), glucose, insulin, c-peptide, leptin, cortisol, dehydroepiandrosterone (DHEA), CD4, CD8 lymphocyte counts and HIV RNA load were measured. RESULTS: Lipodystrophy was observed in only 3.5% of HAART-treated HIV-infected Koreans. No statistical difference in regional fat accumulation or peripheral fat wasting was observed between groups 1, 2 and 3. No statistical difference in triglyceride, total cholesterol, LDL cholesterol, FFA, ApoA1, ApoB, glucose, insulin, C-peptide, leptin, cortisol, and DHEA were observed between groups 1, 2 and 3. HDL cholesterol was significantly lower in HIV-infected individuals compared to controls. CONCLUSIONS: Lipodystrophy, hyperlipidaemia, and insulin resistance are rare metabolic complications of HAART in an oriental HIV-infected group of individuals. These findings warrant further race-specific metabolic complication studies in HIV-infected subjects receiving HAART.

Absorptiometry, Photon↗

PubMed2002

Leptin-replacement therapy for lipodystrophy.

BACKGROUND: The adipocyte hormone leptin is important in regulating energy homeostasis. Since severe lipodystrophy is associated with leptin deficiency, insulin resistance, hypertriglyceridemia, and hepatic steatosis, we assessed whether leptin replacement would ameliorate this condition. METHODS: Nine female patients (age range, 15 to 42 years; eight with diabetes mellitus) who had lipodystrophy and serum leptin levels of less than 4 ng per milliliter (0.32 nmol per milliliter) received recombinant methionyl human leptin (recombinant leptin). Recombinant leptin was administered subcutaneously twice a day for four months at escalating doses to achieve low, intermediate, and high physiologic replacement levels of leptin. RESULTS: During treatment with recombinant leptin, the serum leptin level increased from a mean (+/- SE) of 1.3 +/- 0.3 ng per milliliter to 11.1 +/- 2.5 ng per milliliter (0.1 +/- 0.02 to 0.9 +/- 0.2 nmol per milliliter). The absolute decrease in the glycosylated hemoglobin value was 1.9 percent (95 percent confidence interval, 1.1 to 2.7 percent; P=0.001) in the eight patients with diabetes. Four months of therapy decreased average triglyceride levels by 60 percent (95 percent confidence interval, 43 to 77 percent; P<0.001) and liver volume by an average of 28 percent (95 percent confidence interval, 20 to 36 percent; P=0.002) in all nine patients and led to the discontinuation of or a large reduction in antidiabetes therapy. Self-reported daily caloric intake and the measured resting metabolic rate also decreased significantly with therapy. Overall, recombinant leptin therapy was well tolerated. CONCLUSIONS: Leptin-replacement therapy improved glycemic control and decreased triglyceride levels in patients with lipodystrophy and leptin deficiency. Leptin deficiency contributes to the insulin resistance and other metabolic abnormalities associated with severe lipodystrophy.

Adolescent↗

PubMed2000

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Adolescent↗

PubMed2003

Studies of adipose tissue metabolism in human immunodeficiency virus-associated lipodystrophy.

We studied aspects of metabolism in subcutaneous adipose tissue (SAT) in 40 human immunodeficiency virus (HIV)-infected subjects with and without lipodystrophy and in healthy control subjects. HIV-infected subjects without lipodystrophy had less SAT and visceral adipose tissue (VAT). Glycerol release was higher in both HIV-infected groups, especially those without fat redistribution. Tumor necrosis factor (TNF) release from SAT and serum soluble TNF receptor 2 concentrations were significantly higher in HIV-infected individuals with lipodystrophy. The absolute production of acylation-stimulating protein (ASP) and the percentage conversion of the complement protein to ASP were significantly lower in HIV-infected subjects with lipodystrophy. Further studies are needed to dissect the factors that mediate lipoatrophy in HIV infection.

Adipose Tissue↗

PubMed2004

Mitochondrial DNA levels in fat and blood cells from patients with lipodystrophy or peripheral neuropathy and the effect of 90 days of high-dose coenzyme Q treatment: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Mitochondrial toxicity can be induced by reverse-transcriptase inhibitors, and an association between levels of mitochondrial DNA (mtDNA) per cell and lipodystrophy, peripheral neuropathy, and HIV infection per se has been suggested. Studies aimed at increasing the oxidative capacity in HIV-infected patients have been sparse. METHODS: Levels of mtDNA in fat and peripheral blood mononuclear cells (PBMCs) from 25 HIV infected patients and 10 healthy control subjects were studied with real-time PCR analysis. A placebo-controlled and double-blind design was used to assign individuals to receive either 100 mg of coenzyme Q twice daily for 3 months or a matching placebo regimen. Levels of mtDNA and other parameters were assessed before and after the intervention period. RESULTS: The mean number of mtDNA copies per cell was lower in fat tissue obtained from patients with peripheral neuropathy (1547 mtDNA copies/cell; P=.045), patients with lipodystrophy (1732 mtDNA copies/cell; P=.003) and in HIV patients with no complications associated with highly active antiretroviral therapy (2935 mtDNA copies/cell; P=.078), compared with healthy control subjects (6198 mtDNA copies/cell). No clear difference was seen in mtDNA content in PBMCs. Coenzyme Q therapy improved the general condition of patients (P=.005) and caused a reversible increase in peripheral neuropathy pain (P=.048). Compared with placebo, treatment with coenzyme Q did not result in changes in mtDNA levels in fat cells or in PBMCs after the treatment period. CONCLUSIONS: Levels of mtDNA in fat tissue, but not in PBMCs, were associated with peripheral neuropathy and lipodystrophy. High-dose coenzyme Q therapy increased well-being in asymptomatic HIV-infected patients and those with lipodystrophy, as well as in control subjects, but aggravated pain in patients with peripheral neuropathy.

Adipocytes↗

PubMed2006

Association between physical and echographic fat thickness assessments and a lipodystrophy grading scale in lipodystrophic HIV patients: practical implications.

A simple diagnostic method for detecting in clinical routine HAART-associated lipodystrophy in HIV-infected patients is lacking. We studied the relationships between the scores obtained with a subjective lipodystrophy severity grading scale (LSGS) and standard anthropometric and echographic measurements of the subcutaneous and visceral fat thickness of 74 HIV-infected patients. Patients were divided into four groups according to their LSGS score (0, 1-7, 8-14, 15-21). Significant correlations between the LSGS and the anthropometric and echographic measurements of fat thickness, mainly the limb circumferences (brachial: r= -0.43, p < 0.001; thigh: r= -0.41, p < 0.001), and, especially, the echographically assessed perirenal fat diameters either adjusted (r= 0.46, p < 0.001) or nonadjusted to the body mass index (r= 0.35, p < 0.001) were observed. Significant differences in most of these anthropometric parameters between either the lowest (score 0) and the highest (score 15-21) score groups and the remaining groups were found, but not between the two intermediate groups (scores 1-7 vs. 8-14). This suggests that lipodystrophy should be clinically categorized as absent, mild, or marked, and that even minor changes in physical aspect should be considered as indicative of this disorder. The combination of these subjective and objective parameters could be helpful in the early detection of lipodystrophy in clinical practice.

Adipose Tissue↗

PubMed2005

Altered pre-lamin A processing is a common mechanism leading to lipodystrophy.

Lipodystrophies are a heterogeneous group of human disorders characterized by the anomalous distribution of body fat associated with insulin resistance and altered lipid metabolism. The pathogenetic mechanism of inherited lipodystrophies is not yet clear; at the molecular level they have been linked to mutations of lamin A/C, peroxisome proliferator-activated receptor (PPARgamma) and other seemingly unrelated proteins. In this study, we examined lamin A/C processing in three laminopathies characterized by lipodystrophic phenotypes: Dunnigan type familial partial lipodystrophy, mandibuloacral dysplasia and atypical Werner's syndrome. We found that the lamin A precursor was specifically accumulated in lipodystrophy cells. Pre-lamin A was located at the nuclear envelope and co-localized with the adipocyte transcription factor sterol regulatory element binding protein 1 (SREBP1). Using co-immunoprecipitation experiments, we obtained the first demonstration of an in vivo interaction between SREBP1 and pre-lamin A. Binding of SREBP1 to the lamin A precursor was detected in patient fibroblasts as well as in control fibroblasts forced to accumulate pre-lamin A by farnesylation inhibitors. In contrast, SREBP1 did not interact in vivo with mature lamin A or C in cultured fibroblasts. To gain insights into the effect of pre-lamin A accumulation in adipose tissue, we inhibited lamin A precursor processing in 3T3-L1 pre-adipocytes. Our results show that pre-lamin A sequesters SREBP1 at the nuclear rim, thus decreasing the pool of active SREBP1 that normally activates PPARgamma and causing impairment of pre-adipocyte differentiation. This defect can be rescued by treatment with troglitazone, a known PPARgamma ligand activating the adipogenic program.

3T3-L1 Cells↗

PubMed1988

Lipodystrophy and its treatment.

Lipodystrophy, almost exclusively seen in female patients, causes psychological problems at an early age. In later life, additional complaints are heavy painful legs, edema, and varicose veins. Nearly all patients suffer from alimentary adiposity. Dermolipectomies in general are not advisable because of the resulting large scars and the risk of damaging the lymphatic system. Subcutaneous lipectomy according to the Illouz method can provide good results. Weight loss is a good alternative to liposuction of the upper legs. After sufficient weight loss, only additional liposuction of the trochanteric area and the medial side of the knee is needed. No unpleasant scarring of the leg results. Unfortunately, older patients often require a skin reduction. The results of surgery in the lower legs were, except in 2 patients, good to excellent. The results in the upper legs were disappointing because 9 of 11 patients gained weight again after surgery. Considering this, the preferable treatment now is liposuction of the lower legs, medial side of the knee, and the trochanteric area. Only in cases of ptotic skin on the medial side of the upper legs is skin reduction without lipectomy indicated. Lipodystrophy suggests a disappearance of the subcutaneous fat. When this occurs in the upper part of the body, it is called progressive lipodystrophy. Lipodystrophy is known as an abnormality of the lower half of the female body, swollen by deposition of subcutaneous fat and determined by heredity. It occurs more frequently in the lower social classes and is often accompanied by an alimentary obesity which is a psychological reaction to the disturbed body image.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways.

BACKGROUND: Treatment for HIV-1 infection is complicated by fat redistribution (lipodystrophy). This is associated with insulin resistance concerning glucose uptake. Our aim was to characterize glucose metabolism more comprehensively in HIV-1-infected patients with lipodystrophy. We assessed glucose disposal and its pathways, glucose production, plasma free fatty acid (FFA) levels, and the degree to which these parameters could be suppressed by insulin. METHODS: Six HIV-1-infected men on protease inhibitor-based HAART with lipodystrophy (HIV+LD) were studied. The results were compared with those in six matched healthy male volunteers. Insulin sensitivity was quantified by hyperinsulinemic euglycaemic clamp. Glucose production and uptake were assessed by tracer dilution employing 6,6D(2)-glucose. RESULTS: At post-absorptive insulin concentrations, glucose production was 47% higher in HIV+LD than controls (P = 0.025). During clamp, glucose production was suppressed by 53% in HIV+LD, but by 85% in controls (P = 0.004). Glucose disposal increased in both groups, but by only 27% in HIV+LD versus 201% in controls (P = 0.004). Consequently, insulin-stimulated total glucose disposal was lower in HIV+LD patients (P = 0.006). Non-oxidative glucose disposal as percentage of total disposal did not differ significantly between groups (63% in HIV+LD and 62% in controls). Baseline plasma FFA concentrations were higher (0.60 versus 0.35 mmol/l; P = 0.024), whereas FFA decline during hyperinsulinemia was less (65 versus 85%; P = 0.01) in HIV+LD versus controls. CONCLUSIONS: Post-absorptive glucose production is increased in HIV-1-infected patients with lipodystrophy. Moreover, both the ability of insulin to suppress endogenous glucose production and lipolysis, and to stimulate peripheral glucose uptake and its metabolic pathways is reduced, indicating severe resistance concerning multiple effects of insulin.

Adult↗

PubMed2003

Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy.

OBJECTIVES: Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART). METHODS: We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index. RESULTS: The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease. CONCLUSIONS: These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.

Adiponectin↗

PubMed2003

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.

OBJECTIVE: To determine the expressions of multiple genes in the subcutaneous adipose tissue of HIV-positive, highly active antiretroviral therapy (HAART)-treated patients with and without lipodystrophy. DESIGN AND METHODS: Real-time polymerase chain reaction was used to measure gene expressions in this cross-sectional study. RESULTS: The messenger RNA concentrations of adipose transcription factors (peroxisome proliferator-activated receptor (PPAR) gamma and delta and sterol regulatory element binding protein 1c) were all significantly lower in the lipodystrophic than the non-lipodystrophic group. The mRNA concentration of PPAR-gamma co-activator 1 (PGC-1), which regulates mitochondrial biogenesis, was lower in the lipodystrophic than the non-lipodystrophic group. The mRNA expression of lipoprotein lipase, acyl coenzyme A synthase and glucose transport protein 4 were significantly lower in the lipodystrophic than the non-lipodystrophic group, but the mRNA concentrations of fatty acid transport and binding proteins were similar in both groups. The mRNA concentrations of IL-6 and CD45 (a common leukocyte marker) were significantly higher in the lipodystrophic than the non-lipodystrophic group. CONCLUSION: Multiple alterations characterize gene expression in the subcutaneous adipose tissue of patients with HAART-associated lipodystrophy compared with HIV-positive, HAART-treated patients without lipodystrophy. The low expression of transcription factors inhibits adipocyte differentiation. The low expression of PGC-1 may contribute to mitochondrial defects. In addition, IL-6 and CD45 expressions are increased, the latter implying an excessive number of cells of leukocyte origin in lipodystrophic adipose tissue. Mitochondrial injury and an excess of proinflammatory cytokines may lead to increased apoptosis. All these changes may contribute to the loss of subcutaneous fat in HAART-associated lipodystrophy.

Actins↗

PubMed2001

Lluis Barraquer-Roviralta (1855-1928): Spanish neurologist described progressive lipodystrophy.

Lluis Barraquer-Roviralta, a Spanish neurologist, described the syndrome of progressive lipodystrophy in 1907. This syndrome was subsequently known as Barraquer's syndrome. The main feature of Barraquer's syndrome is the progressive atrophy of the subcutaneous fat of the face. Plastic surgeons are familiar with Barraquer's name because they often correct the facial deformity associated with Barraquer's syndrome. Although plastic surgeons recognize Barraquer for his description of progressive lipodystrophy, his main contributions were to the field of neurology. Barraquer, who is considered the founder of the specialty of neurology in Spain, contributed to the start of neurosurgery in Spain, as well. Barraquer was an expert in diseases of the peripheral nervous system and developed medicines to treat tabes dorsalis. His drawings and photographs of the nervous system were unparalleled. His iconographic collection helped to define the anatomy and pathology of numerous neurological diseases. His pictures were featured in the main neurology textbook of the time and are presently housed in the Museum of Medical History in Spain. During his career at the University of Barcelona Barraquer was well known for his lecturing ability and for training the first neurologists in Spain. In addition to describing progressive lipodystrophy, Barraquer also was the first to describe the grasp reflex of the foot, now known as Barraquer's reflex. Of his remarkable accomplishments, Barraquer is best remembered for his description of two phenomena that now bear his name, Barraquer's reflex and Barraquer's syndrome. Although Lluis Barraquer-Roviralta's main contributions were to the field of neurology, his description of progressive lipodystrophy in 1907 will forever endear him to future generations of plastic surgeons.

History, 19th Century↗

PubMed2004

Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of 'systemic steatosis'.

PURPOSE OF REVIEW: This review addresses a syndrome of dyslipidemia and lipodystrophy that has emerged in HIV-infected patients receiving highly active antiretroviral therapy (HAART). The term 'HIV/HAART associated dyslipidemic lipodystrophy (HADL)' describes this syndrome. Although HAART increases patient survival rates, their increased longevity and dyslipidemias place them at risk for cardiovascular disease. Identification of rationally based therapies requires an understanding of the mechanistic basis of HADL. RECENT FINDINGS: A case definition for HIV lipodystrophy, based on age, gender, duration of HIV disease, serum HDL cholesterol and anthropometry, provides high diagnostic sensitivity and specificity. The dyslipidemias, mainly hypercholesterolemia, hypertriglyceridemia and low-plasma HDL cholesterol, among HIV-infected patients in the pre- and post-HAART eras are summarized. Clinical studies of HADL patients show increased lipolysis, which increases free fatty acid transfer to liver for incorporation into lipoprotein triglycerides that are secreted, and to skeletal muscle where they impair normal insulin signaling. A model of HADL that includes preferential lipolysis in femoral-gluteal fat depots is presented. Relevant therapies include those that inhibit lipolysis (niacin) or increase hepatic fatty acid oxidation (fibrates). SUMMARY: HADL is one of several disorders characterized by dyslipidemia, insulin resistance, and lipodystrophy. The relative acuteness of HADL should facilitate identification of the sequence of metabolic changes that gives rise to the syndrome. Current evidence suggests that deranged energy storage in femoral-gluteal and other peripheral sites is important; the molecular details for the derangement are unknown but are under scrutiny by many investigators.

Animals↗

PubMed2004

Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature.

We describe clinical features, body fat distribution, and prevalence of metabolic abnormalities in 35 patients with acquired partial lipodystrophy (APL) seen by us over 8 years, and also review 220 cases of APL described in the literature. Based on the review and our experience, we propose that the essential diagnostic criterion for APL is the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the "cephalocaudal" sequence, sparing the lower extremities. Analysis of the pooled data revealed that female patients were affected approximately 4 times more often than males. The median age of the onset of lipodystrophy was 7 years. Several autoimmune diseases, in particular systemic lupus erythematosus and dermatomyositis, were associated with APL. The prevalence rates of diabetes mellitus and impaired glucose tolerance were 6.7% and 8.9%, respectively. Approximately 83% of APL patients had low complement (C) 3 levels and the presence of polyclonal immunoglobulin C3 nephritic factor. Twenty-two percent of patients developed membranoproliferative glomerulonephritis (MPGN) after a median of approximately 8 years following the onset of lipodystrophy. Compared with patients without renal disease, those with MPGN had earlier age of onset of lipodystrophy (12.6 +/- 10.3 yr vs 7.7 +/- 4.4 yr, respectively; p < 0.001) and a higher prevalence of C3 hypocomplementemia (78% vs 95%, respectively; p = 0.02). The pathogenesis of fat loss and MPGN in patients with APL remains unclear, but activation of an alternate complement pathway has been implicated. Treating the cosmetic disfigurement by surgical procedures has yielded inconsistent results. The use of thiazolidinediones to treat fat loss in patients with APL remains anecdotal. Prognosis is mainly determined by renal insufficiency due to MPGN.

Adipose Tissue↗

PubMed2006

Lipodystrophy: lessons in lipid and energy metabolism.

PURPOSE OF REVIEW: Lipodystrophies are rare inherited and acquired disorders characterized by the selective loss of adipose tissue. Despite marked phenotypic and genotypic heterogeneity, most lipodystrophic syndromes predispose to similar metabolic complications seen in patients with obesity, such as insulin resistance, diabetes mellitus, hepatic steatosis and dyslipidemia. The purpose of this review is to highlight the current understanding of the mechanisms underlying dyslipidemia in patients with lipodystrophies. RECENT FINDINGS: Marked hypertriglyceridemia and reduced levels of high-density lipoprotein cholesterol are commonly seen, and the severity of these metabolic abnormalities seems to be related to the extent of fat loss. The precise mechanisms by which the lack of adipose tissue causes hypertriglyceridemia remain unknown. Anecdotal kinetic studies in hyperglycemic patients with lipodystrophies have revealed accelerated lipolysis and increased free fatty acid turnover, which drives hepatic triglyceride and very low-density lipoprotein synthesis. Other mechanisms may also be involved in causing dyslipidemia and ectopic triglyceride accumulation in the liver and skeletal muscles that remain to be identified. SUMMARY: Understanding the pathophysiology of dyslipidemia in these rare disorders of lipodystrophies may offer insights into the normal role of adipocytes in maintaining metabolic homeostasis, and its disturbances in common forms of obesity.

Adipose Tissue↗

PubMed2005

Membranous lipodystrophy-like changes in two cases of traumatic lipogranuloma caused by safety belts.

A few cases of subcutaneous nodules with the histological findings of membranous lipodystrophy-like changes have been reported in the literature. However, reports of membranous lipodystrophy-like changes caused by trauma are exceedingly rare. We report two cases of traumatic lipogranuloma that had linear and multiple lesions showing membranous lipodystrophy-like changes and were induced by safety belt trauma after a car accident. These patients showed peculiar changes in their subcutaneous fat and had linear patterned, multiple, nodular lesions with membranous lipodystrophy-like changes caused by trauma.

Adult↗