Charles Najt, PhD

My long-term research interests involve the comprehensive understanding of lipid metabolism, with an emphasis on how alterations in the genes and metabolites in this network contribute to human diseases such as non-alcoholic fatty liver disease (NAFLD), hepatic insulin resistance, cardiovascular disease, and Type 2-Diabetes and how these diseases impact healthspan. My current research targets linking the fatty acids released by Adipose Triglyceride Lipase (ATGL) to gene activation (metabolic state to gene regulation).

I recently showed that Perilipin 5 (PLIN5), a LD protein with multifaceted cellular roles (Figure 1), translocates to the nucleus and forms a transcriptional complex with master regulators of mitochondrial gene expression and mitochondrial biogenesis (Figure 1; point 3).

The Najt Lab is expanding upon our work linking lipid signaling to nutrient sensors by examining PLIN5 in health and lifespan. This is a significant gap in knowledge, as PLIN5 is inversely correlated with age-related metabolic disorders and allows adaptation to environmental stressors, thus directly linking environmental factors to nutrient sensing nodes. Moreover, PLIN5 expression increases with longevity-enhancing interventions such as caloric restriction or intermittent fasting.

In addition to unraveling the mechanism by which PLIN5 impacts health and longevity, work in the Najt lab also focuses on the inflammatory properties of Perilipin 2 (PLIN2). Previous work highlights the anti-inflammatory effects of ablating PLIN2; however the mechanism by which PLIN2 contributes to inflammation is unknown. Given the effects of PLIN2 on inflammation, we plan to examine PLIN2 in the progression of NAFLD, heart disease, and aging. 

Reviewed Journals

• Najt CP, Adhikari S, Heden TD, Cui W, Gansemer ER, Rauckhorst AJ, Markowski TW, Higgins LA, Ker EW, Boyum MD, Alvarez J, Mehra D, Puchner EM, Taylor EB, Mashek DG. Organelle Interactions Compartmentalize Hepatic Fatty Acid Trafficking and Metabolism. Cell Reports. (2023) Vol. 42
• Shang L, Aughey E, Kim H, Heden TD, Wang LU, Najt CP, Esch N, Brunko S, Abrahante JE, Macchietto M, Mashek MM, Fairbanks T, Promislow DL, Neufeld TP, Mashek DG. Systemic Lipolysis Promotes Physiological Fitness in Drosophila Melanogaster. Aging. (2022) Vol. 12
• Heden TD, Chen C, Leland G, Mashek MM, Najt CP, Shang L, Chow LS, Mashek DG. Isolated and Combined Impact of Dietary Olive Oil and Exercise on Markers of Health and Energy Metabolism in Female Mice. J Nutritional Biochem. (2022) Vol. 107 pp. 109040
• Najt CP, Khan SA, Heden TD, Witthuhn BA, Perez M, Mead LE, Franklin MP, Karanja KK, Graham MJ, Mashek MM, Bernlohr DA, Parker L, Chow LS, Mashek DG. Lipid droplet-derived monounsaturated fatty acids traffic via PLIN5 to allosterically activate SIRT1. Molecular Cell. (2020) 77(4), pp.810-824
  
• Seibert JT, Najt CP, Heden TD, Mashek DG, Chow LS. Muscle Lipid Droplets: Cellular Signaling to Exercise Physiology and Beyond. Trends in Endo Metab. (2020) Vol. 31 No. 12
  
• Guerrero GR, Majer LA, Griffin TJ, Higgines L, Najt CP, Perlman DM, Bhargava M. Application of Proteomics in Sarcoidosis. Am J Respir Cell Mol Biol. (2020) 63(6), 727-738
  
• Najt CP, Mashek DG. The Lipid Droplet as a Signaling Node. The Liver: Biology and Pathobiology, (2020) 245-254
  
• Zhang E, Cui W, Lopresti M, Mashek MT, Najt CP, Hu H, Mashek DG.  Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting. Journal of Lipid Res. (2020) 61(30), pp. 338-350.
  
• Mashek DG, Cui W, Shang L, Najt CP. Hepatic Lipid Droplets in Liver Function and Disease. The Liver: Biology and Pathobiology. (2019) Sixth Edition
• Muratore KA, Najt CP, Livezey NM, Marti J, Mashek DG, Arriaga EA. Sizing Lipid Droplets from Adult and Geriatric Mouse Liver Tissue via Nanoparticle Tracking Analysis. Anal Bioanaly Chem. (2018) 

Oral Presentations

• Najt CP, Mashek DG. (2022) Lipid Droplet Signaling in Metabolic Health and Aging. The Midwest Aging Consortium, Virtual.
• Najt CP. (2021) Lipid Droplet Signaling in Metabolic Health and Aging. The Gerontological Society of America, Virtual.
• Najt CP, Mashek DG. (2019) Perilipin 5 Links ATGL-Lipolytic Activity to SIRT1 Signaling. Frontiers of Metabolism – Morgridge Institute for Research, Madison, WI.
  
• Najt CP, Mashek DG. (2018) Perilipin 5 Links ATGL-Lipolytic Activity to SIRT1 Regulation through MUFA Trafficking. Minnesota Diabetes Research Day, Mayo Clinic, Rochester, MN.
  

Poster Presentations

• Najt CP, Mashek DG. (2022) Hepatic Cytosolic and Peridroplet Mitochondria Have Unique Proteomes, Dynamics, and Energetics. Federation of American Societies for Experimental Biology – Lipid Droplet Conference, Ashville, NC.
• Najt CP, Mashek DG. (2018) Perilipin 5 Links ATGL-Lipolytic Activity to PGC-1a /PPAR-a signaling. Federation of American Societies for Experimental Biology – Lipid droplets on the Move in Health and Disease,  Steamboat Springs, CO.