Metabolic Health

 

​​

Research summary:

Research within the ‘Metabolic Health’ research theme focuses on 2 main themes: the respective impacts of (a) exercise-based interventions, and (b) dietary-supplementation-based interventions, upon inflammatory signalling processes relevant to the prevention and management of metabolic conditions such as Type 2 Diabetes, obesity and cardiovascular disease (CVD).


Researchers:

Dr Keith Morris, Reader
Dr Andrew Thomas, Principal Lecturer
Dr Richard Webb, Principal Lecturer/Head of Department
Dr Rachel Adams, Senior Lecturer
Dr Neil Rushmere, Senior Lecturer
Dr Maninder Ahluwalia, Lecturer

Dr Cath Withycombe, Lecturer/Early Career Researcher

Linnet Thekkemuriyil, PhD student
Mike Melhuish, PhD student
Jose-Sofia Ruffino, PhD student
Tom Cullen, PhD student
Nurudeen Hassan, PhD student
Hanan Al-Balushi, MPhil student

 

Completed studentships:

• PhD: Dr Maninder Ahluwalia (2005), Dr Thet Thet Lin (2006), Dr Neenu Singh (2007), Dr Hannah Moir (2009), Dr Lee Butcher (2009), Dr Joanne Caddy (2010), Dr Khalid Al-Muharrami (2010), Dr Suleiman Isa (2011), Dr Lowri Mainwaring (2012), Dr Nia Davies (2013), Dr Jane Thompson (2014)
• MPhil: Mr Steve Potter (2004), Mrs Gertrude Yakeu (2010)
• MD: Dr Aled Roberts MD (2006), Dr Manish Khanolkar MD (2007), Dr Hemanth Bolusani (2013)

Collaborators:

All group members are active members of the Diabetes Research Network Wales; RW sits on the Welsh Government/Valleys Regional Park ‘Health and Wellbeing’ working group.
• Prof Rob Shave, Drs Karianne Backx, Michael G Hughes and David Wasley (School of Sport, Cardiff Metropolitan University)   
• Drs Derek Lang and Phil James (Wales Heart Research Institute, Cardiff University)
• Dr Aled Roberts MD, Professor Marian Ludgate (Clinical Lecturers in Diabetes, Endocrinology and Metabolism, University Hospital Wales. School of Medicine, Cardiff University)
• Drs Malcolm Ward and Julie Bishop (Public Health Wales)
• Ms Jeannie Wyatt-Williams (Wales National Exercise Referral Scheme)
• Dr David Llewellyn (Valleys Regional Park Ltd)
• Mr Brian Davies (Sport Wales Ltd)
• Dr Hannah Moir (Kingston University)
• Professor Abdullah Alangary (King Saud University, Saudi Arabia)

Research Themes and Ongoing Projects:

The effect of exercise on molecular signaling processes and metabolic parameters relevant to the development of metabolic disorders such as Type 2 Diabetes and its complications

• In-vitro and in-vivo studies investigating the mechanisms by which signalling responses are triggered in inflammatory/vascular cells following exercise (or treatment with exercise mimetics), and thus how exercise may regulate inflammatory/vascular function. These include modulation of PPAR activity (and therefore expression of PPAR-regulated genes) due to (i) provision/generation of PPAR ligands; (ii) covalent modification of signalling proteins involved in PPAR signalling due to exercise-associated activation of upstream kinases etc.
• In-vivo studies investigating how exercise changes: (i) gene expression, especially PPAR-activated gene expression (ii) serum lipid profiles (including the qualitative and quantitative analysis of PPAR ligands in the circulation) (iii) markers of inflammation, insulin sensitivity and cardiovascular disease risk.

Ongoing Projects:

Jose Ruffino: “The effects of low-intensity exercise on monocyte differentiation: a protective mechanism against accelerated diabetic atherosclerosis?” – 2010-2015 (PhD project funded by Welsh Government/NISCHR ‘WORD’ scheme).

Publications (2008 onwards):
1.  Davies, N.A., Watkeys, L., Butcher, L., Potter, S., Hughes, M.G.1, Moir, H.2, Morris, K., Thomas, A.W. and Webb, R. “The Roles of Oxidative Stress, Oxidised Lipoproteins and AMPK in Exercise-Associated PPAR Signalling within Human Monocytic Cells” Free Radical Research (in press).
2.  Thomas AW, Davies NA, Moir H, Watkeys L, Ruffino JS, Isa SA, Butcher LR, Hughes MG, Morris K, Webb R. “Exercise-associated generation of PPARγ ligands activates PPARγ signalling events and upregulates genes related to lipid metabolism.” J Appl Physiol. 2012 Mar; 112(5):806-15.
3.  Adams RA, Higgins T, Potter S, Evans SA. “The effect of physical activity on haematological predictors of cardiovascular risk: evidence of a dose response”. Clin Hemorheol Microcirc. 2012;52(1):57-65. doi: 10.3233/CH-2012-1566.
4.  Yakeu, G. Butcher, L. Isa, S. Webb, R. Roberts, A. Thomas, AW, Backx, K., James, P,E Morris, K. (2010) “Low-intensity exercise triggers monocyte polarisation into the M2 anti-inflammatory phenotype” Atherosclerosis 212: 668–673.
5.  Moir, H., Hughes, M.G., Potter, S., Sims, C., Butcher, L.R., Davies, N.A.,Verheggen, K, Jones, K.P., Thomas, A.W., and Webb, R. (2010) “Exercise-induced Immuno-suppression: The Roles of Reactive Oxygen Species and AMPK Dephosphorylation within Immune Cells” J Applied Physiol 108 (5):1284-92.
6.  Butcher, L., Backx, K., Roberts, A., Thomas, A., Webb, R., and Morris, K. (2008): “Low-intensity exercise exerts beneficial effects on plasma lipids via PPAR” Medicine & Science in Sports & Exercise 40 (7), pp. 1–7.
7.  Moir, H., Butcher, L., Jones, K.P., Hughes, M.G., Neale, H., Jia, H., Al-Ismaily, Z., and Webb, R. (2008): "AMPK Inactivation in Mononuclear Cells: A Potential Intracellular Mechanism For Exercise-Induced Immuno-suppression." Applied Physiology, Nutrition and Metabolism 33, p. 75-85

Selected Oral Presentations (2008 onwards):
•  J.S. Ruffino, R. Webb, N.A. Davies, K. Morris, A.W. Thomas. “Participation in a Low Intensity Exercise Programme Promotes M2 Polarisation and Improves Insulin Sensitivity”. 5th International Congress on Prediabetes and the Metabolic Syndrome, Vienna, Austria, April 18-20, 2013.
•  Davies, N., Watkeys, L., Thompson, J., Morris, K., Thomas, AW., Webb, R. (2011) “PPARγ activation in peripheral blood mononuclear cells due to transient increases in reactive oxygen species during exercise: a molecular rationale for prescribing exercise to patients?” J. Diabetes 3 (s1): p. 248. Poster presented at 4th International ‘Pre-Diabetes’ Congress, Madrid, 2011
•  Moir, H., Jones, K.P., Hughes, M.G. and Webb, R.: “AMPK Inactivation in Mononuclear Cells via an AMP:ATP-independent Mechanism – A Potential Explanation for Exercise-Induced Immunosuppression?”. Poster presented at the FASEB J. International Summer Conference, August 2008 (Snekkersten, Denmark).
•  Butcher, L., Webb, R., Backx, K., Roberts, A.W., Thomas, A.W., Morris, K.: “Low-intensity exercise, LDL oxidation and regulation of lipoprotein clearance genes.” Seminar presented at the American College of Sports Medicine’s 55th Annual Meeting, May 2008 (Indianapolis, USA).

Translational Research evaluating the impact of externally-offered exercise programmes on ‘biomarkers’ of metabolic health and cardiovascular/diabetic risk

•  Collaborative work with ‘Valleys Regional Park’ (which comprises over 40 partners, including Groundwork Wales, Welsh Assembly Government, Local Authorities, Sport Wales, Countryside Council for Wales, BTCV and Ramblers Cymru, and which is seeking to regenerate the South Wales valleys primarily though capitalising upon the outstanding natural environmental assets of the area) to evaluate the impact of VRP community-based exercise programmes. 
•  Collaborative work with the Wales National Exercise Referral Scheme (a body which was established in 2007 to standardise exercise referral opportunities across all Welsh Local Authorities/Health Boards) to evaluate the impact of NERS-associated exercise programmes. 
•  Collaborative work with Sport Wales Ltd investigating the impact of intensive training regimes on the inflammatory responses of elite athletes.

Ongoing Projects:
Tom Cullen: “Assessment of the Inflammatory Responses to Acute and Chronic Exercise in Elite Athletes” - 2011-2015 (project funded by EU ‘KESS’ scheme, in collaboration with Sport Wales Ltd).

Publications (2008 onwards):
1.  Cullen, T. Thomas, A.W. Webb, R. Hughes, M.G. “The relationship between interleukin-6 in saliva, venous and capillary plasma, at rest and in response to exercise” Cytokine (in press).
2.  Thompson JES, Webb R, Hewlett P, Llewellyn D, McDonnell BJ. “Matrix metalloproteinase-9 and augmentation index are reduced with an 8-week green-exercise walking programme” J Hypertension (2013) 2 (4): p. 127-33.

Selected Oral Presentations (2008 onwards):
•  Webb, R., Thompson, J.E.S., Hewlett, P., Llewellyn, D., McDonnell, B.J.  “The Effect of an 8-week Green-Exercise Programme on Markers of Cardiovascular Risk”. Poster presented at The Welsh Environment as a National Health Resource national conference (Snowdonia National Park Conference centre, April 2014).
•  Thompson, J.E.S., Webb, R., Hewlett, P., Llewellyn, D., McDonnell, B.J.  “The Effect of an 8-week Moderate-Intensity, Green-Exercise Intervention on MMP-9 and Vascular Haemodynamics”. Seminar presented at 23rd European Meeting on Hypertension and Cardiovascular Protection; European Society of Hypertension (Milan, June 2013).
•  Thompson, J.E.S., Webb, R., Llewellyn, D., Hewlett, P., McDonnell, B.J.  “The Effect of an 8-week Green Exercise Programme on Markers of Mental and Vascular Health”.  Poster presented at 18th Annual Meeting of the European College of Sport Science (ECSS) (Barcelona, June 2013).
•  CULLEN, T., THOMAS, A., WEBB, R., HUGHES, M. “CYTOKINE RELEASE FOLLOWING CONTINUOUS AND INTERVAL EXERCISE OF CONTRASTING VOLUME” Poster presented at 18th Annual Meeting of the European College of Sport Science (ECSS) (Barcelona, June 2013).
•  CULLEN, T., CORBETT, L., PHILLIPS, T., THOMAS, A.W., WEBB, R., HUGHES, M.G. “PLASMA AND SALIVARY INTERLEUKIN-6 RESPONSES TO EXERCISE ARE NOT CORRELATED”. Poster presented at 18th Annual Meeting of the European College of Sport Science (ECSS) (Barcelona, June 2013).
•  Thompson, J.E.S., McDonnell, B.J., Hewlett, P., Webb, R.  “Translating Exercise-Derived Health Benefits from the Laboratory into the Community”.  Seminar presented at 8th Annual Symposium of Health Enhancing Physical Activity (HEPA) Europe, The World Health Organisation (Cardiff, September 2012). 

Nutraceutical Research: Identification and characterisation of natural and synthetic bioactive compounds, with particular focus on the potential of these compounds to modulate inflammatory signalling processes and hence to impact upon metabolic health

•  In-vivo and in-vitro studies on the effect of Conjugated Linoleic Acid, Fenugreek and other natural PPAR ligands on gene expression and cell signaling, especially: (i) vascular markers of inflammation and CVD, (ii) lipid metabolism, (iii) insulin sensitivity, (iv) vascular reactivity in individuals with metabolic syndrome, (v) expression of relevant biomarkers (eg. receptor for AGE) in cultured vascular and endothelial cells. (NB. This includes collaborative work with industrial partners (eg. Obsidian Ltd) investigating the impact of dietary supplementation with products containing the above bio-active compounds on inflammatory responses).
•  In-vitro studies on the effect of Rosiglitazone (and other synthetic PPAR ligands) on gene expression, protein phosphorylation cascades, intracellular calcium handling and vascular contractility/arterial stiffness in cultured vascular and endothelial cells.

Ongoing projects:
1.  Nurudeen Hassan “Fenugreek seeds as sources of Natural PPARgamma ligands” – 2013-2016 (self-funded)
2.  Mike Melhuish: “PPARgamma ligands and cytoskeletal remodelling” – 2008-2015 (part-time project funded by Prince Charles Hospital, Merthyr)
3.  Linnet Thekkemuriyil: “The impact of the natural PPARγ ligand Conjugated Linoleic Acid on endothelial and monocyte-macrophage cell function” (internally funded Cardiff Met project)
4.  Hanan Al-Bulushi: “The impact of the natural PPARγ ligand Conjugated Linoleic Acid on the receptor for Advanced Glycation End-product [RAGE]” (self-funded)
5.  Raya Al-Nasri: “Characterisation of bioactive lipids in camel milk” (in collaboration with Sultan Qaboos University, Sultanate of Oman)

Publications (2008 onwards):
1.  Isa SA, Ruffino JS, Ahluwalia M, Thomas AW, Morris K, Webb R. “M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than other monocyte/macrophage subtypes.” Lipids Health Dis. 2011 Dec 6;10(1):229.
2.  Caddy, J., Isa, S., Mainwaring, LS., Adam, E., Roberts, AW., Lang, D., Morris, KR., Thomas, AW., Webb, R. (2010) “Rosiglitazone induces the unfolded protein response, but has no significant effect on cell viability, in monocytic and vascular smooth muscle cells” Biochem Biophys Res Comm 400: p. 689-695.
3.  Caddy, J., Singh, N., Atkin, L., Ahluwalia, M., Roberts, A.W., Lang, D., Thomas, A.W. and Webb, R. (2008): "Rosiglitazone Transiently Disturbs Calcium Homeostasis in Monocytic Cells" Biochemical Biophysical Research Communications 366, p.149-155.
4.  Morris RHK, Tonks AJ, Jones KP, Ahluwalia MK, Thomas AW, Tonks A, Jackson SK (2008). DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB. Biochem Biophys Res Commun. 370(1):174-8.
5.  Khanolkar M, Morris K, Thomas AW, Evans M (2008) Rosiglitazone produces a greater
reduction in circulating platelet activity compared with gliclazide in patients with type2 diabetes mellitus – an effect probably mediated by direct platelet PPAR gamma activation. Atherosclerosis 197: 718-24

Selected Oral Presentations (2008 onwards):
•  Richard Webb, Suleiman Isa, Keith Morris, Andrew Thomas. “Oxidised LDL-mediated disruption of ER membrane properties and differential sensitivity to lipotoxicity in diverse monocyte/macrophage sub-types: a novel mechanism to underpin the link between obesity and chronic inflammation?” Annual Biochem Soc Symposium - Recent advances in membrane biochemistry 5—7 January 2011 Robinson College, Cambridge, UK                
•  A. Thomas, A., Yakeu, G., Jones, P., Webb, R., Morris, K.  “Conjugated Linoleic Acid (CLA) enhances markers of M2 Polarisation in human monocytic cells” J. Diabetes 3 (s1): p. 27. Seminar presented at 4th International ‘Pre-Diabetes’ Congress, Madrid, 2011.
•  Webb, R., Isa, S., Morris, K., Thomas, AW. (2011) “Enhanced sensitivity to oxidised LDL-mediated lipotoxicity in M2-polarised macrophages: a novel mechanism to underpin the link between obesity and chronic inflammation” J. Diabetes 3 (s1): p. 234. Poster presented at 4th International ‘Pre-Diabetes’ Congress, Madrid, 2011.                      
•  Isa, S.A., Mainwaring, L.S., Webb. R. and Thomas, A.W. (2009): “The Non-Genomic Effects of High Doses of Rosiglitazone on Cell Growth and Apoptosis in Cultured Monocytic Cells” Bayero Journal of Pure and Applied Sciences 2(2): pp.1-8.
•  Mainwaring, L.S, Bolusani, H., Evans, M., Webb, R., Thomas, W., Morris, K. “The natural PPAR-γ ligand CLA regulates RAGE isoform expression in patients with metabolic syndrome”. Poster presented at the 3rd International Congress on Prediabetes and the Metabolic Syndrome, April 2009 (Nice, France).
•  Caddy, J., Thomas, A.W., Atkin, L., Roberts, A.W., Lang, D., Webb, R.: “Rosiglitazone induces ER stress responses, but not apoptosis, in monocytes and vascular smooth muscle cells”. Poster presented at 2nd World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy) October 30 - November 2, 2008, Barcelona, Spain.
•  Mainwaring, L.S., Bolusani, H., Evans, L.M., Webb, R., Morris, K. “The natural PPAR ligand CLA causes genomic and nongenomic effects in leukocytes of patients with metabolic syndrome”. Poster presented at 2nd World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy) October 30 - November 2, 2008, Barcelona, Spain.