Adelaide Medical School
Faculty of Health and Medical Sciences
My research focus is of metabolic health with a particular interest in obesity, lipotoxicity and type 2 diabetes. Currently, as part of my postdoctoral fellowship at CSIRO (Adelaide), I am investigating the role of mitochondrial dysfunction in the pathogenesis of skeletal muscle insulin resistance.
Name of research group: Nutrition & Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide
Brief description of research area: Skeletal muscle mitochondrial dysfunction has been proposed as a key mechanism in promoting insulin resistance. The impairment of mitochondrial oxidative metabolism has been hypothesised to lead to the build-up of lipotoxic lipid species, which, in turn, promote insulin resistance, the hallmark of type 2 diabetes. Currently, I am investigating the role of mitochondrial dysfunction in the pathogenesis of skeletal muscle insulin resistance using an in vitro cell-based model of human primary myotubes. I am looking at the role of nutrients, including fatty acids and amino acids as well as food bioactive derivatives, in modulating pathways and specific proteins and genes known to be important in the regulation of mitochondrial oxidative capacity. Particularly, I am investigating whether nutritional tools able to boost oxidative metabolism might prevent long-chain saturated fatty acids induced insulin resistance.
Title: The impact of medium-chain fatty acids on skeletal muscle insulin signalling and mitochondrial function
Project description: Medium-chain fatty acids have been shown to be β-oxidised at a higher rate compared to long-chain saturated fatty acids suggesting they may be able to modulate mitochondrial function and prevent lipotoxicity-induced insulin resistance. Thus, the aim of this project is to investigate the impact of medium-chain fatty acids on mitochondrial function, insulin sensitivity and the activation of pathways known to regulate mitochondrial biogenesis, function and fatty acid catabolism. This project will employ an in vitro cell-based model of human skeletal muscle myotubes which closely mimics in vivo physiology. Cells will be challenged with medium-chain fatty acids and the following endpoints will be evaluated. Insulin signalling will be assessed by investigating AKT/Protein kinase B phosphorylation by Western blot. This technique will be also used to quantify specific protein of the mitochondrial electron transport chain complexes and the phosphorylation and activation of AMPK which is known as a critical node in promoting oxidative metabolism. Furthermore, we will assess changes in mitochondrial dynamics (i.e. fusion and fission) by fluorescence microscopy using fluorescent probes or immunocytochemistry to target skeletal muscle mitochondria. Finally, the expression of genes involved in skeletal muscle oxidative metabolism and mitochondrial function will be investigated by real-time PCR.
Projects available for: Third Year / Honours / Masters
Location: CSIRO, gate 13 Kintore Avenue, Adelaide, SA5000
Research project start: Semester 1 and 2
Year Citation 2019 McLean, F. H., Campbell, F. M., Sergi, D., Grant, C., Morris, A. C., Hay, E. A., . . . Williams, L. M. (2019). Early and reversible changes to the hippocampal proteome in mice on a high-fat diet.. Nutrition & metabolism, 16, 57.
2019 Sergi, D., Naumovski, N., Heilbronn, L., Abeywardena, M., O Callaghan, N., Lionetti, L., & Luscombe-Marsh, N. (2019). Mitochondrial (dys)function and insulin resistance: From pathophysiological molecular mechanisms to the impact of diet. Frontiers in Physiology, 10, 20 pages.
DOI Scopus1 WoS1 Europe PMC1
2019 McLean, F., Campbell, F., Langston, R., Sergi, D., Resch, C., Grant, C., . . . Williams, L. (2019). A high-fat diet induces rapid changes in the mouse hypothalamic proteome. Nutrition and Metabolism, 16(1), 16 pages.
2019 Munialo, C., Naumovski, N., Sergi, D., Stewart, D., & Mellor, D. (2019). Critical evaluation of the extrapolation of data relative to antioxidant function from the laboratory and their implications on food production and human health: a review. International Journal of Food Science and Technology, 54(5), 1448-1459.
2019 Williams, J., Sergi, D., McKune, A., Georgousopoulou, E., Mellor, D., & Naumovski, N. (2019). The beneficial health effects of green tea amino acid l-theanine in animal models: Promises and prospects for human trials. Phytotherapy Research, 33(3), 571-583.
DOI Scopus4 WoS4 Europe PMC1
2018 Sergi, D., Campbell, F., Grant, C., Morris, A., Bachmair, E., Koch, C., . . . Williams, L. (2018). SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice 06 Biological Sciences 0604 Genetics. Genes and Nutrition, 13(1), 14 pages.
DOI Scopus3 WoS2 Europe PMC2
2018 Sergi, D., Morris, A., Kahn, D., McLean, F., Hay, E., Kubitz, P., . . . Williams, L. (2018). Palmitic acid triggers inflammatory responses in N42 cultured hypothalamic cells partially via ceramide synthesis but not via TLR4. Nutritional Neuroscience, 1-14.
DOI Scopus8 Europe PMC1
2017 Tups, A., Benzler, J., Sergi, D., Ladyman, S., & Williams, L. (2017). Central regulation of glucose homeostasis. Comprehensive Physiology, 7(2), 741-764.
DOI Scopus12 WoS8 Europe PMC7
2013 McGillicuddy, F., Reynolds, C., Finucane, O., Coleman, E., Harford, K., Grant, C., . . . Roche, H. (2013). Long-term exposure to a high-fat diet results in the development of glucose intolerance and insulin resistance in interleukin-1 receptor I-deficient mice. American Journal of Physiology - Endocrinology and Metabolism, 305(7), E834-E844.
DOI Scopus14 WoS13 Europe PMC9
Year Citation 2016 Sergi, D., Kahn, D., Morris, A., & Williams, L. (2016). Palmitic acid induces inflammation in hypothalamic neurons via ceramide synthesis. In PROCEEDINGS OF THE NUTRITION SOCIETY Vol. 75 (pp. E46). CAMBRIDGE UNIV PRESS.
2015 Sergi, D., Morris, A., Drew, J., Campbell, F., Nicol, P., & Williams, L. (2015). A novel hypothalamic protein regulated by high fat diet and leptin. In PROCEEDINGS OF THE NUTRITION SOCIETY Vol. 74 (pp. E190). CAMBRIDGE UNIV PRESS.
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