Multiple symmetric lipomatosis (MSL) is a rare disease first described by Brodie in 1846(1). Madelung reported data on 33 cases in 1888 (2), but the classical description of the disease is attributed to Launois and Bensaude who published a detailed account of 65 cases in 1898 (3). The literature on MSL is dominated by research on alcoholic men with a reported incidence of 1/25,000 in the Italian population (4). Nonalcoholics and women are also affected (5-7). Over 270 cases are reported in the literature with an age range varying from 20 to 71 years; two cases have been reported in children (8, 9).
Individuals with MSL have increased fat, usually in a symmetrical distribution either on the neck, upper back (buffalo hump) or interscapular region, on the upper arms or chest, in the mediastinum or thighs, sparing the distal limbs (10). The fat in MSL is thin and watery when removed by needle biopsy unless the individual has undergone numerous liposuction or excision surgeries. When transporting fat in media, the fat will stick to the top of a polystyrene container, distinguishing this fat from AD or FML. Because the appearance and location of the lipomatosis can vary, MSL has been divided into three types: (6, 11): Type I or diffuse lipomatosis of the neck (‘horsecollar lipomata’); Type II or multiple symmetric lipomata of the shoulder girdle, the upper arms, the thorax, the thighs and sometimes the abdomen giving the patients the so called ‘pseudoathletic’ appearance; and Type III or a rare type with preponderance of the lipomatosis in the thigh girth (‘gynecoid type’). Women tend to have Type II and III (10).
Associated disorders include liver disease, hyperlipidemia including elevated high density lipoprotein (HDL) levels (in patients with a history of alcohol use), hypertriglyceridemia, hypothyroidism, diabetes mellitus, and neurological changes (12). MSL is an inherited disorder associated with mitochondrial mutations in a few familial cases, (13, 14) however, Klopstock et al. (15) found mitochondrial mutations in only 2 of 12 patients studied. In addition, Chalk et al. found no mitochondrial pathology or mutations in four siblings with MSL with a pattern favoring autosomal recessive (16).
Morbidity and mortality in MSL is high with sudden non-coronary death accounting for a large percentage of deaths in one series (5). The neuropathology of MSL is a distal axonal demyelination different from that associated with alcohol intake (12, 16, 17) and impairment of autonomic function has been suggested as a possible cause of sudden deat. This impairment seems to be prevalently parasympathetic and not related to a high alcohol intake (18, 19).
Adipose stem cells from MSL tissue express uncoupling protein (UCP)-1 similar to brown adipose tissue, but fail to increase UCP-1 in response to noradrenaline even though MSL cells express b1-, b2- and b3-adrenergic receptors (AR) (20). In agreement, catecholamines did not induce lipolysis in MSL cells as measured by glycerol release(21). Because a-AR were not evaluated in this study, these data suggest either a dysregulation in b-AR in the MSL tissue or elevated levels of a-adrenergic receptors.
Adipose tissue express endothelial nitric oxide synthase (NOS) (22) and inducible NOS (iNOS) (23, 24). Noradrenaline did not stimulate expression of iNOS in MSL cells, however, a NO donor inhibited proliferation of these cells and a selective inhibitor of NOS stimulated proliferation. These data suggest a normal response of MSL tissue to NO but defective sympathetic signaling. The sympathetically inducible protein PGC-1, involved in mitochondrial biogenesis in brown adipose tissue (BAT) and other cell types(25), was also not stimulated by noradrenaline in MSL cells as in BAT from rats, supporting a defect in sympathetic nervous system stimulation of MSL tissue (20).
In our survey of 110 individuals with AD, we asked specifically about excess fat on the upper back called a ‘buffalo hump’. Twenty-five (22.7%) individuals had positive responses and 80% of these described the fat as painful. The presence of a buffalo hump can be found in HIV-associated lipodystrophy (26-29) and in MSL (10, 15, 30). It has proposed that the fat in MSL is in the same spectrum as the buffalo hump in HIV-associated lipodystrophy (31). We hypothesize that in fat disorders, especially in AD and MSL, that there can be overlap in the types of abnormal fat present and that more clinical data on these disorders and their overlap is needed as well as laboratory data to distinguish these disorders so that treatments, that might be different for different disorders, can be considered.
References
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