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Lipodystrophy, pancreatitis, and eosinophilia.

Two patients suffering from partial lipodystrophy, pancreatitis, and recurrent eosinophilia are described. In one patient the duodenum and the terminal ileum were narrowed, the appearances suggesting eosinophilic gastroenteritis: bilateral hydronephrosis was also present without ureteric obstruction. An association between lipodystrophy and renal disease is recognized; it is possible that there is also an association between lipodystrophy and pancreatitis, and eosinophilia with or without an intestinal lesion may be a further association.

Adult↗

Single nucleotide polymorphisms of RXRA encoding retinoid X receptor alpha.

Retinoic X receptor alpha (RXRA), encoded by RXRA, plays a key role in development and metabolism, specifically in adipocyte biology, glucose homeostasis, and intestinal cholesterol balance. RXRA is also a positional candidate gene for Berardinelli-Seip congenital lipodystrophy. We report the systematic screening of RXRA coding regions by genomic DNA sequencing, which has resulted in the identification of three novel single-nucleotide polymorphisms.

3' Untranslated Regions↗

Heart positive: design of a randomized controlled clinical trial of intensive lifestyle intervention, niacin and fenofibrate for HIV lipodystrophy/dyslipidemia.

Dyslipidemia and insulin resistance occur in a large proportion of HIV-infected patients treated with highly active antiretroviral therapy (HAART); anthropomorphic changes, such as lipoatrophy and central obesity, occur in a subset of patients. This cluster of clinical features, which is termed HIV lipodystrophy, places patients at increased risk for cardiovascular disease. Currently, there is no consensus on the appropriate therapy for the management of HIV lipodystrophy for which the underlying defects are enhanced lipolysis, impaired fat oxidation, increased hepatic VLDL-triglyceride synthesis and secretion, and impaired disposal of intestinally-derived lipoprotein-triglycerides. We describe the design of a randomized, placebo-controlled trial to compare the effects of usual care to diet, exercise and lipid-lowering drugs on lipid profiles of patients with HIV lipodystrophy. The trial will randomize 200 patients into five groups. Outcomes of usual care, diet and exercise alone or in combination with niacin, fenofibrate or both medications will be compared after six months. Unique aspects of the design include an interactive Internet Diet Management system to increase ATP-III recommended dietary compliance for metabolic syndrome, and a supervised program of aerobic and resistance exercises. The study is powered to detect a 20% decrease in triglycerides with the lifestyle intervention and an additional 20% improvement with the addition of niacin and/or fenofibrate. Secondary outcomes include assessment of lipid profile changes, LDL and HDL particle size, plasma cholesterol ester transport protein activity, visceral and subcutaneous fat distribution, glucose tolerance, insulin resistance, and leptin and adiponectin levels.

Adult↗

[Mesenteric lipodystrophy].

This case report describes the clinic and pathologic findings of an inflammatory pseudotumor of the mesentery in a 43 years old male. Previous to the hospital admission he had several episodes of intestinal occlusion and an abdominal mass. Computed tomography and mesenteric angiography were very helpful. Laboratory tests were unspecific, and the final diagnosis was obtained after surgery and histologic study of the lesion. We review published literature on inflammatory pseudotumors.

Adult↗

Diarrhea-associated HIV-1 APIs potentiate muscarinic activation of Cl- secretion by T84 cells via prolongation of cytosolic Ca2+ signaling.

Aspartyl protease inhibitors (APIs) effectively extend the length and quality of life in human immunodeficiency virus (HIV)-infected patients, but dose-limiting side effects such as lipodystrophy, insulin resistance, and diarrhea have limited their clinical utility. Here, we show that the API nelfinavir induces a secretory form of diarrhea in HIV-infected patients. In vitro studies demonstrate that nelfinavir potentiates muscarinic stimulation of Cl(-) secretion by T84 human intestinal cell monolayers through amplification and prolongation of an apical membrane Ca(2+)-dependent Cl(-) conductance. This stimulated ion secretion is associated with increased magnitude and duration of muscarinically induced intracellular Ca(2+) transients via activation of a long-lived, store-operated Ca(2+) entry pathway. The enhanced intracellular Ca(2+) signal is associated with uncoupling of the Cl(-) conductance from downregulatory intracellular mediators generated normally by muscarinic activation. These data show that APIs modulate Ca(2+) signaling in secretory epithelial cells and identify a novel target for treatment of clinically important API side effects.

Adult↗

[X-ray computed tomographic aspects of mesenteric panniculitis].

Mesenteric panniculitis also known as lipodystrophy is an inflammatory condition of adipose tissue. A case of a 55 year old, female who presented a weight loss and a tender palpable mass located in the left flank is reported. CT patterns were not specific but might suggest the diagnosis: fatty mass, with a higher density than subcutaneous fat, located in the root of the mesentery and surrounding mesenteric vessels without distoting them. Intestinal loops were only pulled in periphery. This signs are not always present and even in this typical pattern mesenteric panniculitis could not be differentiated from liposarcoma. Thus an histological proof was needed. The evolution was good, with resolution of the abdominal pain. The knowledge of this rare Radioclinical syndrome should prevent any aggressive therapy.

Abdominal Neoplasms↗

Diffuse mesenteric lipodystrophy (massive fat necrosis) in a cat.

Clinical, radiographic, and pathological findings of diffuse mesenteric lipodystrophy in a 3-year-old, female domestic short-haired cat are described. The animal had fallen from a height of approximately 20 metres 6 weeks previously, after which it developed respiratory distress and anorexia. The cat was thin, exhausted and had rapid, shallow, open-mouthed breathing. Serial upper gastrointestinal contrast radiographs showed a prolonged transit time of the contrast medium due to restricted gastric emptying, and filling defects of the duodenojejunal portions of the small intestines. The cranial abdominal cavity contained large, firm, white masses that adhered to most of the anterior abdominal organs. The intestinal walls were completely surrounded by large, hard, lobulated masses of lipomatous tissue. The masses were characterised histologically by extensive areas of coagulative necrosis of adipocytes containing foci of saponification. The lesions resembled those of massive fat necrosis or lipomatosis in cattle, pigs and deer.

Accidental Falls↗

Long-term changes in adipose tissue in human disease.

Redistribution of white adipose tissue is a long-term symptom of several chronic diseases. Although the roles of adipocytes in acute illness have been thoroughly studied, how or why short-term responses of adipose tissue to disease sometimes produce long-term redistribution, and the causal relationship between the anatomical changes and the associated metabolic syndromes are poorly understood. The present paper reviews explanations for the redistribution of adipose tissue after infection with HIV, and in Crohn's disease; both conditions that share the peculiarity of selective expansion of certain adipose depots while others are depleted. HIV adipose tissue redistribution syndrome (HARS) develops gradually after several months of infection with the HIV both in untreated patients and in those taking protease inhibitors and nucleoside reverse transcriptase inhibitors. Some current theories about the causes of HARS are critically assessed, and reasons presented for implicating local interactions between the immune system and perinodal adipocytes. Some evolutionary aspects of conspicuous long-term changes in the distribution of human adipose tissue are discussed. Adipose tissue acts as a social signal, indicating dietary history and previous exposure to pathogens. A distinctive symptom of Crohn's disease is selective enlargement of the mesenteric adipose tissue near the diseased lymph nodes and intestine. Perinodal adipocytes have site-specific properties not found in adipocytes from nodeless depots, such as perirenal and epididymal, that may equip them to interact locally with lymph-node lymphoid cells, making polyunsaturated fatty acids selectively and rapidly available to activated immune cells. Studies of the time course of activation of perinodal adipocytes via the lymph nodes they enclose indicate that prolonged or frequent stimulation recruits more adipocytes to control by immune cells, which may lead to selective enlargement of node-containing depots. These concepts suggest hypotheses about HARS and the anomalous development of mesenteric adipose tissue in Crohn's disease that could form the basis for further investigations.

Adipose Tissue↗