Andrew J. Lutkewitte, Ph.D.

Professional Background

Andrew Lutkewitte, Ph.D., obtained his undergraduate studies in Biology and Chemistry at Butler University in 2011 before completing his doctorate in Integrative Physiology at the Indiana University School of Medicine in 2016. His post-doctoral research at the Washington University School of Medicine was centered on liver lipid metabolism and insulin sensitivity with a focus on evaluating the metabolic responses to fasting, adipose lipolysis, obesity, and hepatic lipid accumulation. In 2023, Dr. Lutkewitte joined the University of Kansas Medical Center as an Assistant Professor and a member of the KU Diabetes Institute.

The ultimate goal of Dr. Lutkewitte's research is to investigate the relationship between functional adipose tissue mass and systemic metabolism with particular emphasis on hepatic function.

• BS, Biology and Chemistry, Butler University, Indianapolis, IN
• PhD, Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN
• Post Doctoral Fellowship, Obesity and Lipid metabolism, Washington University School of Medicine, St. Louis, MO

• The Obesity Society, Member, 2022 - Present

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Research

Overview

Obesity affects over a billion people worldwide and has been identified as a leading risk factor for developing metabolic dysfunction-associated steatotic liver disease (MASLD), as well as insulin resistance (IR) and type two diabetes mellitus (T2DM). Paradoxically, the marked absence of adipose tissue (lipodystrophy) also leads to these comorbidities. This observation suggests that adipose tissue function directly regulates systemic metabolism rather than adipose tissue mass. Several studies in human patients have shown that pathophysiological adipose tissue (defined by adipose tissue insulin resistance, inflammation, and fibrosis) drives the development of hepatic diseases such as dyslipidemia, hepatic steatosis, metabolic dysfunction-associated steatohepatitis, and even fibrosis.
Our long-term goal is to understand the mechanistic basis by which adipose tissue crosstalk with the liver regulates hepatic metabolism. We have two current research projects ongoing. [1.] In adipocytes, triglycerides are generated through the glycerol-3-phosphate pathway. The penultimate step is the generation of diacylglycerol through the phosphatidic acid phosphohydrolase activity of lipin 1 (gene name Lpin1). We have shown that in humans, adipose, LPIN1 expression positively correlates with insulin sensitivity and negatively correlates to hepatic DNL. In line with this, we have generated mice lacking lipin 1 in adipose tissue, which display a lean yet metabolically unhealthy phenotype that includes hepatic steatosis and insulin resistance. Our ongoing research is to determine the mechanisms of these phenotypes. [2.] Although the liver maintains a unique ability to regenerate following injury or loss, this capacity is reduced in parallel with the severity of the MASLD disease progression. Therefore, understanding the underlying mechanisms that regulate hepatic regeneration in the context of obesity (a worsening pandemic) could provide novel insight into potential new therapies. We have developed two mouse models with dysfunctional adipocytes to understand the dynamic relationship between healthy adipose tissue and hepatic growth. We aim to assess how acute adipose tissue loss drives hepatic expansion and how this impacts the pathophysiology of the liver in response to increased lipid load.
Together, these studies will enhance our understanding of how adipose tissue and the liver communicate to establish metabolic equilibrium and could lead to innovative therapies for metabolic disorders.

• Dysfunctional adipose tissue’s role in hepatic metabolic disease, NIH/NIGMS, PI
• Adipose-Specific Phosphatidic Acid Phosphatase Activity of Lipin 1 Regulates Systemic Insulin Sensitivity, NIH/NIDDK, PI

• Kumari, R, Ponte, M., E, Franczak, E, Prom, J., C, O'Neil, M., F, Sardiu, M., E, Lutkewitte, A., J, Christenson, L., K, Shankar, K, Morris, E., M, Thyfault, J., P. 2024. VCD-induced menopause mouse model reveals reprogramming of hepatic metabolism.. Molecular metabolism, 82, 101908
• LaPoint, A, Singer, J., M, Ferguson, D, Shew, T., M, Renkemeyer, M., K, Palacios, H, Field, R, Shankaran, M, Smith, G., I, Yoshino, J, He, M, Patti, G., J, Hellerstein, M., K, Klein, S, Brestoff, J., R, Finck, B., N, Lutkewitte, A., J. 2023. Adipocyte lipin 1 is positively associated with metabolic health in humans and regulates systemic metabolism in mice.. bioRxiv : the preprint server for biology
• Lutkewitte, A., J, Singer, J., M, Shew, T., M, Martino, M., R, Hall, A., M, He, M, Finck, B., N. 2021. Multiple antisense oligonucleotides targeted against monoacylglycerol acyltransferase 1 (Mogat1) improve glucose metabolism independently of Mogat1.. Molecular metabolism, 49, 101204
• Lutkewitte, A., J, Schweitzer, G., G, Kennon-McGill, S, Clemens, M., M, James, L., P, Jaeschke, H, Finck, B., N, McGill, M., R. 2018. Lipin deactivation after acetaminophen overdose causes phosphatidic acid accumulation in liver and plasma in mice and humans and enhances liver regeneration.. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 115, 273-283
• Ferguson, D, Eichler, S., J, Yiew NKH, Colca, J., R, Cho, K, Patti, G., J, Shew, T., M, Lutkewitte, A., J, Mukherjee, S, McCommis, K., S, Niemi, N., M, Finck, B., N. 2023. Mitochondrial pyruvate carrier inhibition initiates metabolic crosstalk to stimulate branched chain amino acid catabolism.. Molecular metabolism, 70, 101694
• Martino, M., R, Gutiérrez-Aguilar, M, Yiew NKH, Lutkewitte, A., J, Singer, J., M, McCommis, K., S, Ferguson, D, Liss KHH, Yoshino, J, Renkemeyer, M., K, Smith, G., I, Cho, K, Fletcher, J., A, Klein, S, Patti, G., J, Burgess, S., C, Finck, B., N. 2022. Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.. Cell reports, 39 (4), 110733
• Singer, J., M, Shew, T., M, Ferguson, D, Renkemeyer, M., K, Pietka, T., A, Hall, A., M, Finck, B., N, Lutkewitte, A., J. 2022. Monoacylglycerol O-acyltransferase 1 lowers adipocyte differentiation capacity in vitro but does not affect adiposity in mice.. Obesity (Silver Spring, Md.), 30 (11), 2122-2133
• Habibi, M, Ferguson, D, Eichler, S., J, Chan, M., M, LaPoint, A, Shew, T., M, He, M, Lutkewitte, A., J, Schilling, J., D, Cho, K., Y, Patti, G., J, Finck, B., N. 2023. Mitochondrial Pyruvate Carrier Inhibition Attenuates Hepatic Stellate Cell Activation and Liver Injury in a Mouse Model of Metabolic Dysfunction-associated Steatotic Liver Disease.. bioRxiv : the preprint server for biology