Publications by authors named "Loubna Al Sadat"

2 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

Longitudinal changes on liver proton density fat fraction differ between liver segments.

Quant Imaging Med Surg 2021 May;11(5):1701-1709

Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany.

Background: To study the spatial heterogeneity of liver fat fraction changes during a long-term lifestyle intervention study using magnetic resonance imaging (MRI).

Methods: Thirty-two subjects underwent two MRI-scans in a span of one year. A chemical shift encoding-based water-fat separation method was applied to measure liver proton density fat fraction (PDFF) maps. The PDFF changes in the two liver lobes and the Couinaud segments were compared with the mean liver PDFF change.

Results: The slope of the relationship between mean liver PDFF changes and PDFF liver lobe changes was higher in the right compared to the left lobe (slope =1.08, slope =0.93, P<0.001). The highest slope of agreement between PDFF changes in each specific liver segment and mean liver PDFF changes was observed in segment VII (slope =1.12). The lowest slope of agreement between PDFF changes in each specific liver segment and mean liver PDFF changes was observed in segment I (slope =0.77).

Conclusions: Larger PDFF changes in the right liver lobe were observed compared to PDFF changes in the left liver lobe (LLL) in subjects with both increasing and decreasing mean liver PDFF after one year. The results are in line with the existing literature reporting a heterogeneous spatial distribution of liver fat and highlight the need to spatially resolve liver fat fraction changes in longitudinal studies.
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http://dx.doi.org/10.21037/qims-20-873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047351PMC
May 2021
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