Arranging Fat: UM Bioartography
Callie A.S. Corsa, PhD Scientific Writer, JB Ashtin; Former Postdoctoral Fellow, Molecular & Integrative Physiology
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ave you ever looked through the microscope and been amazed at what you saw? As scientists who do this routinely, we may take it for granted, but microscopic images are often complex, intriguing, and beautiful. The UofM BioArtography program was developed to collect artistic scientific images and share them with the greater public community to spark curiosity and spread scientific knowledge. In 2019, during my postdoc in the lab of Dr. Ormond MacDougald, I was analyzing several H&E-stained slides from various organs while phenotyping a novel mouse model we developed when I noticed something very strange under the microscope. These mice had almost no body fat (white adipose tissue), very few adipocytes in their bone marrow, and very abnormal brown adipose tissue, so we also took a close look at their skin to see if the dermal adipose tissue was affected. Consistent with our hypothesis, we saw a huge reduction in the number of dermal adipocytes in these mice. As I looked closer, I also noticed some very strange characteristics in the layers of the skin. The dermis and epidermis were significantly thicker compared with control mice, and the hair follicles were huge and abnormally shaped.
This mouse model was created to mimic the most common inherited partial lipodystrophy, familial partial lipodystrophy type 2 (FPLD2). FPLD2 is characterized by a progressive loss of adipose tissue and the development of lipodystrophy-related diabetes and non-alcoholic fatty liver disease. FPLD2 is known to be caused by mutations in the LMNA gene, but the traditional methods that researchers use to study a disease caused by genetic mutations in people – looking at what happens to cultured cells or mice with those same mutations – hasn’t worked well with FPLD2. Examinations of cultured cells with dysfunctional or absent LMNA have yielded conflicting results (1), (2), and a LMNA mutation that causes dramatic disease in humans produces very mild effects when overexpressed in the fat cells of mice.(3) In order to study this condition in mice, we created an entirely new mouse model in which an important functional region of the LMNA gene was deleted specifically in adipocytes. The lipodystrophic phenotypes observed in these mice beautifully mimicked the human FPLD2 adipose tissue
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Physiology Matters
loss, but why would the skin be severely affected when the genetic deletion was only targeted to adipocytes? The subcutaneous white adipose tissue from these mice also had a very strange morphology, with the appearance of dense fibrotic tissue between the cells and mild hyperplasia of the mammary epithelial cells. We consulted multiple pathologists to figure out what was happening in the tissue, but none of them could explain what we saw – though they all agreed it was incredibly odd. We still have no idea what caused these strange phenotypes in the skin, but it made for some very interesting images! By sharing this image, we would like to promote awareness of rare diseases and the lack of available therapies, along with showcasing the beauty of the microscopic world. The next time you’re looking through the microscope, take a minute to marvel at the beautiful details you’re viewing, and consider sending a few of your images to UofM Bioartography! • 1. Boguslavsky et al., Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 15(4): 653-663, 2006. 2. Oldenburg et al., Deregulation of Fragile X-related protein 1 by the lipodystrophic lamin A p.R482W mutation elicits a myogenic gene expression program in preadipocytes Hum Mol Genet 23(5): 11511162, 2014. 3. Wojtanik et al., The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation J Lipid Res 50(6): 1068-1079, 2009.
Visit http://www.bioartography.com to view a collection of art for purchase. Please use discount code MIP at checkout for 15% off, valid through 6/30/21.
