LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells.

OBJECTIVE: The term Multiple Symmetric Lipomatosis (MSL) describes a heterogeneous group of rare monogenic disorders and multifactorial conditions, characterized by upper-body adipose masses. Biallelic variants in LIPE encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate LIPE-related clinical features and pathophysiological determinants. METHODS: A gene panel was used to identify pathogenic variants. The disease features were reviewed at the French lipodystrophy reference center. The immunohistological, ultrastructural, and protein expression characteristics of lipomatous tissue were determined in surgical samples from one patient. The functional impact of variants was investigated by developing a model of adipose stem cells (ASCs) isolated from lipomatous tissue. RESULTS: We identified new biallelic LIPE null variants in three unrelated patients referred for MSL and/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction. CONSLUSIONS: Biallelic LIPE null variants result in a multisystemic disease requiring multidisciplinary care. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy/MSL phenotype and associated metabolic complications. Detailed ophthalmological examination could reveal retinal damage, further pointing to the nervous tissue as an important disease target.

Diagnostic and Therapeutic Management of Post-Gastric Bypass Chronic Diarrhea: a Systematic Review.

There is a lack of recommendation regarding exploration and treatment of chronic diarrhea following gastric bypass, while it is a common side effect of this surgery. The electronic databases MEDLINE and EMBASE were searched until July 2018. Of the 553 articles identified, 35 articles were included. Intestinal bacterial overgrowth and pancreatic exocrine insufficiency are the main etiologies of diarrhea following gastric bypass. The diagnostic approach must begin by eliminating infectious causes of diarrhea. Exocrine pancreatic insufficiency can be diagnosed with fecal fat quantification or fecal elastase 1 level evaluation. A positive lactulose breath test confirms suspicion of small intestine bacterial overgrowth. In conclusion, we propose sequential exploration and treatment of the possible etiologies of diarrhea depending on clinical symptoms.