Cellular and Molecular Metabolism

Selected Publications

Lindegaard B, Abilgaard J, Heywood SE, Pedersen BK, Febbraio MA. Role of Interleukin-18 in the maintenance of metabolic homeostasis is influenced by female sex hormones. Mol Metab doi: 10.1016/j.molmet.2018.04.005, 2018. [E-pub ahead of print].

Lancaster GI, Langley KG, Anton Berglund N, Kammoun HL, Reibe S, Estevez E, Weir J, Mallett NA, Pernes G, Conway JRW, Lee MK, Timpson P, Murphy AJ, Masters SL, Gerondakis S, Bartonicek N, Kaczorowski DC, Dinger ME, Meikle PJ, Bond PJ, Febbraio MA. TLR4 is not a receptor for saturated fatty acids but mediates lipid-induced inflammation by re-programming macrophage metabolism. Cell Metab 27: 1096-1110, 2018. Accompanied by Research Highlight: Morris A. Palmitate is not a TLR4 agonist Nature Reviews Endocrinology https://doi.org/10.1038/s41574-018-0029, 2018.

Kammoun HL, Allen TL, Henstridge DC, Barre S, Coll R, Cron L, Reibe S, Murphy AJ, Bensellam, M, Laybutt R, Butler MS, Robertson AB, O’Neill LA, Cooper MA, Febbraio MA. Evidence against a role for NLRP3-driven inflammation in db/db mice. Mol Metab 10: 66-73, 2018.

Whitham M, Parker BL, Friedrichsen M, Hingst JR, Hjorth M, Hughes WE, Egan CL, Cron LNN, Watt KI, Kuchel RP, Jayasooriah N, Estevez E, Petzold T, Suter CM, Gregorevic P, Kiens B, Richter EA, James DE, Wojtaszewski JFP, Febbraio MA.  Extracellular vesicles provide a means for tissue cross talk during exercise. Cell Metab 27: 237-251, 2018.

Man K, Liao Y, Gabriel S, Gloury R, Preston S, Henstridge DC, Marc Pellegrini M, Berberich-Siebelt F, Febbraio MA, Shi W, Kallies A. Transcription factor IRF4 promotes CD8+ T cell exhaustion and limits the development of memory-like T cells during chronic infection. Immunity 47: 1129-1141, 2017.

Lee-Young RS, Hoffman N, Murphy KT, Henstridge DC, Iliades P, Zivanovic B, Hong YH, Colgan T, Kraakman MJ, Bruce CR, Gregorevic P, Kingwell BA, McConell GK, Wadley GD, Lynch GS, Drummond GR, Febbraio MA. Glucose-6-phosphate dehydrogenase activity contributes to the regulation of glucose uptake in skeletal muscle. Mol Metab. 5: 1083-1091, 2016.

Whitham M, Febbraio MA. The ever expanding myokinome: discovery challenges and therapeutic implications. Nature Rev. Drug Discov. 15: 719-729, 2016.

Lancaster GI, Kammoun KL, Kraakman MJ, Kowalski GM, Bruce CR, Febbraio MA. PKR is not obligatory for high fat diet-induced obesity and its associated metabolic and inflammatory complications. Nature Comm. DOI: 7: 10626  doi:10.1038/ncomms10626, 2016.  Accompanied by Research Highlight: Greenhill C. PKR is not involved in metabolic diseases. Nature Rev Endo doi:10.1038/mrendo. 2016.

Murphy AJ, Kraakman MJ, Lawlor KE, Wentworth JM, Vasanthakumar A, Gerlic M, DiRago L, Cengia L, Metcalf D, Roberts AW, Vince JE, Harrison LC, Kallies A, Kile BT, Croker BA, Febbraio MA, Masters SL. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome. Cell Metab. 23: 155-164, 2016 Accompanied by Research Highlight: Netea MG, Joosten LAB. The NLRP1-IL-18 Connection: A stab in the back of obesity-induced inflammation. Cell Metab. 23: 6-7, 2016.

Selathurai A, Burch ML, Kowalski GM, Sepulveda P, Risis S, Lee-Young RS, Meikle PJ, Genders AJ, McGee SL, Watt MJ, Russell AP, Frank M, Jackowski S, Febbraio MA, Bruce CR. Elimination of the CDP-ethanolamine pathway in skeletal muscle has pronounced effects on lipid homeostasis and mitochondrial oxidative capacity without altering insulin sensitivity. Cell Metab. 21: 718-730, 2015.

Kraakman MJ, Kammoun HL, Allen TL, Deswaerte V, Henstridge DC, Estevez E, Matthews VB, Neill B, White DA, Murphy AJ, Peijs L, Yang C, Rises S, Bruce CR, Du X-J, Bobik A, Lee-Young RS, Kingwell BA, Vasanthakumar A, Shi W, Kallies A, Lancaster GI, Rose-John S, & Febbraio MA. Blocking IL-6 trans-signaling prevents high fat diet-induced adipose tissue macrophage recruitment and does not exacerbate weight gain, liver steatosis or insulin resistance. Cell Metab 21: 403-416, 2015.

Sapra G, Tham YK, Cemerlang N, Matsumoto A, Kiriazis H, Bernardo BC, Henstridge DC, Ooi JYY, Pretorius L, Boey EJH, Lim L, Sadoshima J, Meikle PJ, Mellet NA, Woodcock EA, Marasco S, Ueyama T, Dy X-J, Febbraio MA*, & McMullen JR*. The small molecule, BGP-15, protects against heart failure and atrial fibrillation in mice. Nature Comm. DOI: 10.1038/ncomms6705, 2014 . *MAF and JRM are joint corresponding authors. Accompanied by Research Highlight: Crunkthorn S. Insulin sensitizer protects the heart. Nature Rev Drug Disc. 14 (2): 93, 2014.

Lancaster GI, & Febbraio MA. The immune-modulating role of exercise in metabolic disease. Trends Immunol 35:262-269, 2014.

Febbraio MA. Role of interleukins in energy homeostasis: implications for metabolic disease. Trends Endocrinol & Metab 25: 312-319, 2014.

Henstridge DC, Bruce CR, Tory K, Kolonics A, Drew BG, Chung J, Watson N, Estevez E, Gardner T, Lee-Young RS, Connor T, Watt MJ, Hargreaves M, McGee SL, Hevener AL, & Febbraio MA. Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance. Diabetes 63: 1881-1894, 2014.

Mauer J, Chaurasia B, Goldau J, Vogt MC, Schmitz J, Ruud J, Nguyen KD, Theuric S, Hausen C, Bronneke HS, Estevez, E, Allen TL, Febbraio MA, Chawla A, Wunderlich FT, & Breuning JC. IL-6 signaling in myeloid cells promotes alternative macrophage activation to limit obesity-associated insulin resistance. Nature Immunol. 15: 423-430, 2014. Accompanied by Research Highlights: Reilly SM, Saltiel AR. Countering inflammatory signals in obesity. Nature Immunol. 15: 410-411, 2014; Covarrabias AJ, Horng T. IL-6 strikes a balance in metabolic inflammation. Cell Metab. 19: 898-899, 2014;  Bordon Y. Immunometabolism: IL-6 the resistance fighter. Nature Rev Immunol. 14: 282-283, 2014.

Man, K, Miasari M, Shi W, Xin A, Henstridge DC, Preston S, Pellegrini M, Belz GT, Smyth GK, Febbraio MA, Nutt SL, & Kallies A. IRF4 is essential for T cell receptor affinity mediated metabolic programming and clonal expansion of T cells. Nature Immunol 14: 1155-1165, 2013.

Lindegaard B, Matthews VB, Brandt C, Hojman P, Allen TL, Estevez E, Watt MJ, Bruce CR, Mortensen O, Syberg S, Rudnicka C, Abildgaard J, Pilegaard H, Hidalgo J, Ditlevsen S, Algreen T, Madsen AN, Pedersen BK, & Febbraio MA. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice. Diabetes 62: 3064-3074, 2013.

Teperino R, Amann S, Bayer M, McGee SL, Loipetzberger A, Conner T, Jaeger C, Kammerer B, Winter W, Wiche G, Dalgaard K, Riter J, Gaster M, Lee Young R, Febbraio MA, Knauf C, Cani PD, Aberger F, Penninger JM, Pospisilik JA, &  Esterbauer H. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat. Cell 151: 414-426, 2012. Accompanied by Research Highlight: Lee KY, Kahn CR. Turning on brown fat and muscle metabolism: hedging your bets. Cell 151: 248-250, 2012.

Bruce CR, Risis S, Babb JR, Yang C, Kowalski GM, Selathurai A, Lee-Young RS, Wier JM, Yoshioka K, Takuwa Y, Meikle PJ, Pitson SM, & Febbraio MA. Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high fat fed mice. Diabetes 61: 3148-3155, 2012. Accompanied by Research Highlight: Gorski J. Ceramide and insulin resistance: how should the issue be approached? Diabetes 61: 3081-3083, 2012.

Pedersen BK, & Febbraio MA. Muscle, exercise and obesity: skeletal muscle as a secretory organ. Nature Rev Endocrinol. 8: 457-465, 2012.

Gehrig S, van der Poel C, Sayer TA, Schertzer JD, Henstridge DC, Church JE, Lamon S, Russell AP, Davies KE, Febbraio MA, & Lynch GS. HSP72 preserves muscle function and slows progression of severe muscular dystrophy. Nature 484: 384-398, 2012. Accompanied by Research Highlight: Tse, MT. Neuromuscular disorders: Turning up the heat (shock) Nature Rev Drug Disc. 11 (5): 354, 2012.

Whitham M, Chan MHS, Matthews VB, Prelovsek O, Lunke S, El-Osta A, Wunderlich FT, Pal M, Broenneke H, Bruning J, Lancaster GI, & Febbraio MA. Contraction-induced IL-6 gene transcription in skeletal muscle is regulated by c-jun terminal kinase/Activator protein -1.  J Biol. Chem. 287: 10771-10779, 2012.

Nicholls HT, Kowalski G, Risis S, Zaffino LA, Watson N, Kanellakis P, Watt MJ, Bobik A, Bonen A, Febbraio M, Lancaster GI, & Febbraio MA. Haematopoietic cell restricted deletion of CD36 reduces high fat diet-induced macrophage infiltration and insulin resistance in adipose tissue. Diabetes 60:1100-1110, 2011.

Matthews VB, Allen TL, Risis S, Chan MHS, Watson N, Zaffino LA, Babb J, Boon J, Meikle PJ, Jowett J, Watt MJ, Jannson J-O, Bruce CR, & Febbraio MA. Interleukin-6 deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 53: 2431-2441, 2010.

Yuen DYC, Dwyer RM, Matthews VB, Drew BG, Southgate RJ, Neill B, Kingwell BA, Clark MG, Rattigan S, & Febbraio MA. IL-6 attenuates insulin mediated increases in endothelial cell signaling, but augments skeletal muscle insulin action via differential effects on TNF-α expression. Diabetes 58:1086–1095, 2009.

Pedersen BK, & Febbraio MA. Muscle as an endocrine organ – focus on muscle-derived IL-6. Physiol. Rev. 88: 1379-1406, 2008.

Chung J, Nguyen A-K, Henstridge DC, Holmes AG, Chan MHS, Mesa JL, Lancaster GI, Southgate RJ, Bruce CR, Duffy S, Vigh L, Horvath I, Mestril R, Watt MJ, Hooper PD, Kingwell BA, Hevener A, & Febbraio MA. HSP72 protects against obesity-induced insulin resistance. Proc Natl Acad Sci USA 105: 1739-1744, 2008. Accompanied by Research Highlight: Stevens, K. Melting away. Nature Med. 14, 123, 2008.

Febbraio MA. gp130 receptor ligands: potential therapeutic targets in obesity J. Clin Invest. 117:  841-849, 2007.

Steinberg GR, Michell BJ, van Denderen B, Watt MJ, Fam BC,  Andrikopoulos S, Gorgun CZ, Proietto J, Carling D, Hotamisligil, GS, Febbraio MA, Kay, TW, & Kemp BE. Tumor necrosis factor-α induced skeletal muscle insulin resistance involves the suppression of AMP-kinase signaling. Cell Metab 4: 465-474, 2006.

Carey AL, Steinberg GR, Macaulay SL, Thomas WJ, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Petersen BK, & Febbraio MA. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55: 2688-2697, 2006.

Watt MJ, Dzamko N, Thomas W, Rose-John S, Ernst M, Carling D, Kemp BE,  Febbraio MA. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nature Med 12: 541-548, 2006. Accompanied by Research Highlight: Ahima RS. Overcoming insulin resistance with CNTF Nature Med. 12, 511-512, 2006.

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