Multiple symmetric lipomatosis

Klopstock, Thomas; Naumann, Markus; Schalke, B.; Bischof, F.; Seibel, Peter; Kottlors, Michael; Eckert, P; Reiners, Karlheinz; Toyka, Klaus V.; Reichmann, Heinz

doi:10.1212/wnl.44.5.862

Cited by 109 publications

(68 citation statements)

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“…12 MSL has been related to high levels of alcohol consumption, but the etiopathogenetic role of alcohol is not yet known. In the study of Klopstock et al, 13 abnormal mitochondrial status has been observed in MSL patients. Yet, Heckmann et al 14 have reported a case of a female, heavy drinker, MSL patient with mild frontal atrophy, without neuropsychological impairment or mitochondrial abnormalities.…”

Section: Discussionmentioning

confidence: 93%

Unusual Cases of Multiple Symmetrical Lipomatosis with Neurological Disorders

Triantafyllou

Zalonis²,

Kararizos³

et al. 2009

Clinical Medicine & Research

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Section: Discussionmentioning

confidence: 93%

Unusual Cases of Multiple Symmetrical Lipomatosis with Neurological Disorders

Triantafyllou

Zalonis²,

Kararizos³

et al. 2009

Clinical Medicine & Research

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“…MSL is a pathology characterized by the formation of lipomas containing abnormal white adipocytes smaller than normal adipocytes showing a multivesicular phenotype (1,2,7). Moreover, biochemical analyses have shown that cytochrome c oxidase activity is impaired in muscles from patients with MSL (8), supporting the fact that the disease is linked to mitochondrial dysfunction (6,9). The role of mitochondria in the lipid metabolism of white adipose tissue was also strengthened in the pathogenesis of lipodystrophy syndromes induced by highly active antiretroviral therapies known to impair mitochondrial functions (3).…”

mentioning

confidence: 87%

Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid β-oxidation and glucose

Vankoningsloo

Piens

Lecocq

et al. 2005

Journal of Lipid Research

142

118

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Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype observed in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the molecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity is still poorly understood. Here, we found that preadipocytes incubated with inhibitors of mitochondrial respiration such as antimycin A (AA) accumulate TG vesicles but do not acquire specific markers of adipocytes. Although the uptake of TG precursors is not stimulated in 3T3-L1 cells with impaired mitochondrial activity, we found a strong stimulation of glucose uptake in AA-treated cells mediated by calcium and phosphatidylinositol 3-kinase/Akt1/glycogen synthase kinase 3 ␤ , a pathway known to trigger the translocation of glucose transporter 4 to the plasma membrane in response to insulin. TG accumulation in AA-treated cells is mediated by a reduced peroxisome proliferator-activated receptor ␥ activity that downregulates muscle carnitine palmitoyl transferase-1 expression and fatty acid ␤ -oxidation, and by a direct conversion of glucose into TGs accompanied by the activation of carbohydrate-responsive element binding protein, a lipogenic transcription factor. Taken together, these results could explain how mitochondrial impairment leads to the multivesicular phenotype found in some mitochondria-originating diseases associated with a dysfunction in fat metabolism. The role of mitochondria in lipid homeostasis has been strongly emphasized in recent studies focusing on mitochondrial respiratory deficiency. Indeed, chronic mitochondrial dysfunction can lead to diseases characterized by lipid metabolism disorders and pathological triglyceride (TG) accumulation in several cell types (1-3). Genetic mitochondrial pathologies usually result from point mutations or deletions in mitochondrial DNA that finally impair oxidative phosphorylation capacity (4). Interestingly, some mitochondrial disorders affect lipid-metabolizing tissues such as muscular and adipose tissues. For example, the myoclonic epilepsy with ragged red fibers (MERRF) syndrome, commonly caused by a point mutation in the mitochondrial tRNA Lys -encoding gene (A8344G), is associated with myopathy, TG accumulation in muscles (5), and, in some cases, multiple symmetrical lipomatosis (MSL) (2, 6). MSL is a pathology characterized by the formation of lipomas containing abnormal white adipocytes smaller than normal adipocytes showing a multivesicular phenotype (1, 2, 7). Moreover, biochemical analyses have shown that cytochrome c oxidase activity is impaired in muscles from patients with MSL (8), supporting the fact that the disease is linked to mitochondrial dysfunction (6, 9). The role of mitochondria in the lipid metabolism of white adipose tissue was also strengthened in the pathogenesis of Abbreviations: AA,...

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“…MSL is thought to be inherited through mitochondrial mutations in a few familial cases including multiple deletions of mitochondrial DNA, and the myoclonus epilepsy and raggedred fibers (MERRF) tRNA(Lys) A>G(8344) mutation [56,57] . Klopstock et al found mitochondrial mutations in only 2 of 12 patients studied [50] .…”

Section: Msl Inheritancementioning

confidence: 99%

Rare adipose disorders (RADs) masquerading as obesity

2012

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Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidencebased data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.

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Multiple symmetric lipomatosis

Cited by 109 publications

References 0 publications

Unusual Cases of Multiple Symmetrical Lipomatosis with Neurological Disorders

Unusual Cases of Multiple Symmetrical Lipomatosis with Neurological Disorders

Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid β-oxidation and glucose

Rare adipose disorders (RADs) masquerading as obesity

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