Michael D. Thompson, M.D., Ph.D.

Assistant Professor
Pediatrics
Endocrinology/Metabolism

Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-454-6051

  • thompsonmd@wustl.edu

  • Understanding the impact of parental obesity on offspring liver disease and the mechanisms that mediate the development of chronic diseases in adulthood

Research Abstract:

In our lab, we utilize mouse models of maternal and paternal obesogenic diet exposure to study the effect on offspring metabolic disease. Others and we have identified that offspring exposed to maternal obesogenic diet develop more severe NAFLD and have associated changes in bile acid homeostasis. Current work in the lab is focused on understanding the molecular mechanisms involved in these changes as well as the mechanisms for transmission of these phenotypes across generations. These studies include evaluation of the microbiome, which is passed from Mom to offspring at birth and known to play a primary role in obesity-associated conditions including NAFLD. We are also undertaking epigenetic analyses to define the sustained changes to the hepatic methylome and chromatin architecture after parental obesogenic diet exposure. These studies focus on unbiased sequencing approaches including ATAC-seq, MeDIP-seq, and RRBS. While the primary focus is on NAFLD, we have also identified that offspring exposed to maternal obesogenic diet are at increased risk of cholestatic liver disease suggesting that the underlying changes induced by parental obesity may have implications across multiple types of liver disease. Studies are ongoing to develop model of cholestatic liver disease following parental obesogenic diet exposure including primary sclerosing cholangitis, which is associated with inflammatory bowel disease.

We have also begun to study the impact of parental obesogenic diet exposure on the development of cancer in the offspring. NAFLD is a precursor for the development of hepatocellular carcinoma. Ongoing work is evaluating whether the predisposition to develop NAFLD leads to increased development of HCC after maternal obesogenic diet exposure. Likewise, maternal obesogenic diet induces changes to the microbiome and sensitivity to development of intestinal inflammation. We are evaluating the impact of these changes on development of colon cancer in the offspring.

The long-term goal of the lab is to identify and develop preventive measures that target developmental programming and thus mitigate the increased risk for chronic disease observed in offspring exposed to parental obesogenic diet. We are currently evaluating the impact of parental and offspring exercise as a therapeutic approach to target developmental programming. Preliminary evidence in the literature indicates that exercise in the absence of parental obesity plays a protective role from development of NAFLD in the offspring. Our studies will identify whether exercise (parental or offspring) plays a protective role in the setting of parental obesity driven offspring NAFLD risk and ultimately the mechanisms involved in protection.

Selected Publications:

Thompson MD. Developmental Programming of NAFLD by Parental Obesity. Hepatol Commun. 2020;4(10):1392-1403.

Ferey J, Boudoures AL, Reid M, Drury A, Scheaffer S, Modi Z, Kovacs A, Pietka T, DeBosch BJ, Thompson MD, Diwan A, Moley KH. Maternal High-Fat, High-Sucrose Diet Induces Transgenerational Cardiac Mitochondrial Dysfunction Independent of Maternal Mitochondrial Inheritance. Am J Physiol Heart Circ Physiol. 2019.

Thompson MD, Derse A, Ferey J, Reid M, Xie Y, Christ M, Chatterjee D, Nguyen C, Harasymowicz N, Guilak F, Moley KH, Davidson NO. Transgenerational Impact Of Maternal Obesogenic Diet On Offspring Bile Acid Homeostasis And Non-Alcoholic Fatty Liver Disease. Am J Physiol Endocrinol Metab. 2019.

Thompson MD, Moghe A, Cornuet P, Marino R, Tian J, Wang P, Ma X, Abrams M, Locker J, Monga SP, Nejak-Bowen K. β-Catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis. Hepatology. 2018;67(3):955-971.

Last Updated: 4/30/2021 6:25:56 PM

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