Publications by authors named "Sophie Strobel"

3 Publications

  • Page 1 of 1

Linking the obesity rs1421085 variant circuitry to cellular, metabolic, and organismal phenotypes in vivo.

Sci Adv 2021 Jul 21;7(30). Epub 2021 Jul 21.

Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire OX11 0RD, UK.

Variants in FTO have the strongest association with obesity; however, it is still unclear how those noncoding variants mechanistically affect whole-body physiology. We engineered a deletion of the rs1421085 conserved cis-regulatory module (CRM) in mice and confirmed in vivo that the CRM modulates and gene expression and mitochondrial function in adipocytes. The CRM affects molecular and cellular phenotypes in an adipose depot-dependent manner and affects organismal phenotypes that are relevant for obesity, including decreased high-fat diet-induced weight gain, decreased whole-body fat mass, and decreased skin fat thickness. Last, we connected the CRM to a genetically determined effect on steroid patterns in males that was dependent on nutritional challenge and conserved across mice and humans. Together, our data establish cross-species conservation of the rs1421085 regulatory circuitry at the molecular, cellular, metabolic, and organismal level, revealing previously unknown contextual dependence of the variant's action.
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http://dx.doi.org/10.1126/sciadv.abg0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294759PMC
July 2021

A MicroRNA Linking Human Positive Selection and Metabolic Disorders.

Cell 2020 10 14;183(3):684-701.e14. Epub 2020 Oct 14.

Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.

Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.
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http://dx.doi.org/10.1016/j.cell.2020.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092355PMC
October 2020

Adherence to infliximab therapy in inflammatory bowel disease patients in a real-life setting.

J Dig Dis 2017 Oct;18(10):566-573

Inserm U954 and Department of Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France.

Objective: To assess adherence to infliximab (IFX) therapy in inflammatory bowel disease patients, to investigate reasons for non-adherence and to identify predictors for non-adherence.

Methods: This observational study was conducted in two French referral university hospitals between 1 September and 31 October, 2011. Patients were systematically asked if they had already delayed or missed an IFX perfusion since the beginning of the treatment and about the reasons for their non-adherence.

Results: Of the 162 included patients (121 Crohn's disease [CD], 41 ulcerative colitis), 87 (53.7%) reported a delay of at least one IFX injection and 14 (8.6%) missed at least one IFX perfusion since the beginning of the treatment. The overall non-adherence rate was 54.3%. Pooling all misses, the main reasons for non-adherence were pregnancy (33.3%), intentional non-adherence (20%) and forgetfulness (13.3%). Pooling all delays, the main reasons for non-adherence were professional constraints (46.9%), infections (17.3%) and travels (14.3%). Perineal disease was associated with IFX delays (P = 0.0007, odds ratio 4.0), whereas active CD/UC was associated with IFX misses (P = 0.0258, OR = 5.4).

Conclusions: The overall non-adherence rate for IFX use was 54.3%. Professional constraints and intentional non-adherence were the leading causes of non-adherence. Perineal disease and active CD were negatively related to adherence.
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http://dx.doi.org/10.1111/1751-2980.12539DOI Listing
October 2017
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