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Browsing by Author "Laville, Martine"
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Item Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity(American Diabetes Association, 2013-11) Carobbio, Stefania; Hagen, Rachel M.; Lelliott, Christopher J.; Slawik, Marc; Medina-Gomez, Gema; Tan, Chong-Yew; Sicard, Audrey; Atherton, Helen J.; Barbarroja, Nuria; Bjursell, Mikael; Bohlooly-Y, Mohammad; Virtue, Sam; Tuthill, Antoinette; Lefai, Etienne; Laville, Martine; Wu, Tingting; Considine, Robert V.; Vidal, Hubert; Langin, Dominique; Oresic, Matej; Tinahones, Francisco J.; Manuel Fernandez-Real, Jose; Griffin, Julian L.; Sethi, Jaswinder K.; López, Miguel; Vidal-Puig, Antonio; Medicine, School of MedicineThe epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.Item International consensus on the diagnosis and management of dumping syndrome(Nature Publishing group, 2020-05-26) Scarpellini, Emidio; Arts, Joris; Karamanolis, George; Laurenius, Anna; Siquini, Walter; Suzuki, Hidekazu; Ukleja, Andrew; Van Beek, Andre; Vanuytsel, Tim; Bor, Serhat; Ceppa, Eugene; Di Lorenzo, Carlo; Emous, Marloes; Hammer, Heinz; Hellström, Per; Laville, Martine; Lundell, Lars; Masclee, Ad; Ritz, Patrick; Tack, Jan; Surgery, School of MedicineDumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.