- 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.
- Breznik, JA, Naidoo, A, Foley, KP, Schulz, C, Lau, TC, Loukov, D et al.. TNF, but not hyperinsulinemia or hyperglycemia, is a key driver of obesity-induced monocytosis revealing that inflammatory monocytes correlate with insulin in obese male mice. Physiol Rep. 2018;6 (23):e13937. doi: 10.14814/phy2.13937. PubMed PMID:30548217 PubMed Central PMC6286899.
- Cavallari, JF, Anhê, FF, Foley, KP, Denou, E, Chan, RW, Bowdish, DME et al.. Targeting macrophage scavenger receptor 1 promotes insulin resistance in obese male mice. Physiol Rep. 2018;6 (22):e13930. doi: 10.14814/phy2.13930. PubMed PMID:30485705 PubMed Central PMC6260912.
- Yao, Y, Jeyanathan, M, Haddadi, S, Barra, NG, Vaseghi-Shanjani, M, Damjanovic, D et al.. Induction of Autonomous Memory Alveolar Macrophages Requires T Cell Help and Is Critical to Trained Immunity. Cell. 2018;175 (6):1634-1650.e17. doi: 10.1016/j.cell.2018.09.042. PubMed PMID:30433869 .
- Foley, KP, Zlitni, S, Denou, E, Duggan, BM, Chan, RW, Stearns, JC et al.. Long term but not short term exposure to obesity related microbiota promotes host insulin resistance. Nat Commun. 2018;9 (1):4681. doi: 10.1038/s41467-018-07146-5. PubMed PMID:30409977 PubMed Central PMC6224578.
- Sharma, A, Maurya, CK, Arha, D, Rai, AK, Singh, S, Varshney, S et al.. Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes. Biochim Biophys Acta Mol Basis Dis. 2019;1865 (1):136-146. doi: 10.1016/j.bbadis.2018.10.036. PubMed PMID:30391544 .
- Poznanski, SM, Barra, NG, Ashkar, AA, Schertzer, JD. Immunometabolism of T cells and NK cells: metabolic control of effector and regulatory function. Inflamm. Res. 2018;67 (10):813-828. doi: 10.1007/s00011-018-1174-3. PubMed PMID:30066126 .
- Kim, TT, Parajuli, N, Sung, MM, Bairwa, SC, Levasseur, J, Soltys, CM et al.. Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mice. Am. J. Physiol. Endocrinol. Metab. 2018;315 (4):E511-E519. doi: 10.1152/ajpendo.00471.2017. PubMed PMID:29870676 .
- 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. 2018;23 (4):570. doi: 10.1016/j.chom.2018.03.006. PubMed PMID:29649447 PubMed Central PMC5899819.
- Rebalka, IA, Cao, AW, Raleigh, MJ, Henriksbo, BD, Coleman, SK, Schertzer, JD et al.. Statin Therapy Negatively Impacts Skeletal Muscle Regeneration and Cutaneous Wound Repair in Type 1 Diabetic Mice. Front Physiol. 2017;8 :1088. doi: 10.3389/fphys.2017.01088. PubMed PMID:29311999 PubMed Central PMC5742241.
- Stearns, JC, Simioni, J, Gunn, E, McDonald, H, Holloway, AC, Thabane, L et al.. Intrapartum antibiotics for GBS prophylaxis alter colonization patterns in the early infant gut microbiome of low risk infants. Sci Rep. 2017;7 (1):16527. doi: 10.1038/s41598-017-16606-9. PubMed PMID:29184093 PubMed Central PMC5705725.