- Microbiota, obesity and diabetes
The inability to respond to insulin is a major cause of type 2 diabetes. This insulin resistance precedes overt diabetes and provides a therapeutic window to prevent the disease. Obesity is the main cause of insulin resistance and inflammation has emerged as a key link between obesity and insulin resistance. How does obesity cause inflammation and how does inflammation cause insulin resistance leading to diabetes? My laboratory is interested in understanding these problems in ImmunoMetabolism and how dietary and bacterial factors connect immunology and metabolism.
My laboratory uses physiology in genetic mouse models coupled with cell biology and biochemistry to understand the inflammatory basis of metabolic disease. Using our ImmunoMetabolism expertise, we collaborate with immunologists, microbiologists and gastroenterologists in order to understand how the food we eat and the bacteria that colonize us can cause (or prevent) metabolic diseases. This work is particularly interested in how the bacterial cell wall component, peptidoglycan, and dietary factors such as fat propagate inflammation and alter metabolism via nucleotide oligomerization domain (Nod) proteins. This research aims to understand modifiable sources of inflammation that promotes diabetes during obesity.
My laboratory is also connects inflammation in muscle diseases (i.e. myopathies). This builds on a long standing interest in basic science and therapeutics targeted to muscle using both endocrine and gene therapy approaches. Given that statin drugs are the first line treatment for obesity/diabetes related cardiovascular disease, we are particularly interested in immunity and statin-induced myopathy. This work is coming full circle and now looking at how statins and other drugs alter inflammation relevant to diabetes.
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- Duggan, BM, Foley, KP, Henriksbo, BD, Cavallari, JF, Tamrakar, AK, Schertzer, JD et al.. Tyrosine kinase inhibitors of Ripk2 attenuate bacterial cell wall-mediated lipolysis, inflammation and dysglycemia. Sci Rep. 2017;7 (1):1578. doi: 10.1038/s41598-017-01822-0. PubMed PMID:28484277 PubMed Central PMC5431485.
- Cavallari, JF, Fullerton, MD, Duggan, BM, Foley, KP, Denou, E, Smith, BK et al.. Muramyl Dipeptide-Based Postbiotics Mitigate Obesity-Induced Insulin Resistance via IRF4. Cell Metab. 2017;25 (5):1063-1074.e3. doi: 10.1016/j.cmet.2017.03.021. PubMed PMID:28434881 .
- Thevaranjan, N, Puchta, A, Schulz, C, Naidoo, A, Szamosi, JC, Verschoor, CP et al.. Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Cell Host Microbe. 2017;21 (4):455-466.e4. doi: 10.1016/j.chom.2017.03.002. PubMed PMID:28407483 PubMed Central PMC5392495.
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- Denou, E, Marcinko, K, Surette, MG, Steinberg, GR, Schertzer, JD. High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity. Am. J. Physiol. Endocrinol. Metab. 2016;310 (11):E982-93. doi: 10.1152/ajpendo.00537.2015. PubMed PMID:27117007 PubMed Central PMC4935139.