Professor Brian Oldfield
Professor - Department of Physiology
BSc (Hons), PhD
Address
Department of Physiology
Monash University VIC 3800
Australia
Located
Room F216, Building 13F (Physiology) at Clayton Campus
Tel: +61 3 990 52507
Fax: +61 3 990 29500
Email: Brian.Oldfield@monash.edu
Background
Professor Brian Oldfield completed his PhD in 1979 and after postdoctoral studies at McGill University, Montreal and Columbia University, New York he established international credentials while at the Howard Florey Institute, Melbourne in the neuroendocrinology of fluid balance. For the last 10 years his interests have shifted to focus more on the ingestion of food and the development of obesity rather than the ingestion of fluids. The transition between these related fields is now complete and he is now an established member of the international obesity research community with regular invitations to speak about the work of his group at international meetings.
Research Interests
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Since his recruitment to the Department of Physiology in 2005, Professor Oldfield has formed a team of Metabolic Neuroscientists focused on the way the brain controls both ends of the energy balance spectrum – on the one hand, its role in the control of food intake and on the other, the way it controls energy expended in metabolism. His group has widespread interests between these two poles of the energy balance equation ranging from the way reward pathways in the brain mediate the craving of highly palatable foods, through the brains involvement in the determination of the distribution of fat to the part played by the brain in anorexia nervosa. He has a major interest in understanding the mechanisms underling bariatric surgery and his group has established the first rodent model of the adjustable gastric band. This work is supported by commercial funding derived from the US based Pharmacuetical and Appliance Compnay, Allergan.
Current Honorary Appointments and Positions
- Member of the Scientific Advisory Board of the Centre for Obesity Research and Education (CORE)
- Head, Basic Research Division of the Centre for Obesity Research and Education
- Australasian Representative of the International Neuroendocrine Federation (until December 2009)
- Chair of the Executive of the Victorian Obesity Consortium (VOC)
- Chair of the Executive of the Monash Obesity Research Initiative (MORI)
- Chair of Basic Science & member of the Sponsorship and finance sub-committee of the Australian and New Zealand Obesity Society (ANZOS)
Current Honours Projects
1. Adjustable Gastric Band (AGB) surgery, an animal model – does tightening your belt help to enhance weight loss?
Laporascopic adjustable gastric band (LAGB) surgery in human patients is emerging as one of the most effective means of initiating and maintaining weight loss. In fact, surgical approaches have created a new “gold standard” where they can offer between 20-30% weight loss (and 60-70% loss of excess weight) whereas the best pharmacological therapies are hovering at about 5% loss of excess body weight. While there is often a misconception that the band which is placed around the upper part of the stomach in the human patient acts solely to limit the amount of food allowed into the stomach, this is not true. The best evidence to date is that there is either a 
hormonal or neural signal activated by the tightening of the band which alerts the brain to reduce hunger. We have no idea of the nature of this signal or the changes in the brain that it mediates to reduce hunger.
This series of projects uses a miniaturized band fitted to the rat stomach and a range of approaches to map the potential pathways to the brain and the changes in gene expression that are initiated by adjustment of the band. Specifically, individual projects will examine i) the potential activation by the band of neural links between the stomach and the brain via the vagus nerve, ii) the changes in levels of gut derived hormones in the blood that may activate the brain following tightening of the band, iii) the changes in activation of feeding related pathways as shown in fMRI following tightening of the band, iv) the changes in expression of feeding related genes in the brain and expression of incretins and other peptides and hormones in the stomach following tightening of the band v) changes in energy expenditure following tightening of the band. These experimental approaches will provide valuable information about the mechanisms underlying the effectiveness of this approach in human patients.
2. Blockade of cannabinoids in the brain – a role in the control of obesity 
The cannabinoids have been known for many centuries to increase food intake – most recently recognized as the need to ingest highly palatable foods after smoking cannabis. These largely anecdotal observations have been incorporated into the treatment of patients suffering from cancer and AIDS in order to promote appetite. Over the last few years, blockers of the endogenous actions of the receptors to cannabinoids in the brain, the so called CB1 receptor antagonists, have become the number 1 candidates to combat obesity. This is thought to be largely through changes in food intake but the role of these agents in determining levels of energy breakdown and the level of body fat is unknown. In contrast to the role of the CB1 receptor in appetite and energy expenditure, the CB2 receptor is important for regulation of the immune system. Although poorly understood, obesity is now accepted as a state of inflammation whereby obese individuals have increased circulating and adipose tissue expression of inflammatory markers, similar to what is seen during an infection. This opens the possibility that CB2 receptor agonists, known to inhibit the immune system, may prove beneficial for the treatment of obesity-related inflammatory conditions such as type 2 diabetes
3. The biological basis of anorexia nervosa? Impact of an animal model
While obesity and its related issues occupy centre stage amongst so called eating disorders, anorexia nervosa is situated at the other end of the spectrum and represents a very significant problem amongst affected individuals. Nearly 20% of those diagnosed with restrictive anorexia nervosa will die as a result of the disorder. There is no effective treatment and there is only a sketchy understanding of the etiology of the disorder. It is clear that psychological and environmental issues play a role but what is not apparent is the extent to which there is an underlying biological basis of anorexia nervosa. In this vein, insight into these mechanisms or the brain regions involved may enable the development of therapeutic strategies.
This series of projects is based on an activity based rodent model of anorexia which mimics a number of the key characteristics of the disease. It is our intention to exploit this model to investigate the biological substrates involved as well as the potential to pharmacologically reverse the weight loss associated with anorexia nervosa.
4. Antipsychotic drug (APD) induced weight gain – understanding the mechanisms behind the increases in weight and development of diabetes in schizophrenic patients taking APDs
Commonly overlooked when considering individuals who are overweight or obese are those who gain weight and develop diabetes directly as a result of taking medications for psychoses including schizophrenia. This is a debilitating situation which often results in patients discontinuing medications or running the risk of developing metabolic syndrome. These disadvantages are tolerated because of the effectiveness of the drugs in alleviating antipsychotic symptoms.
We have a series of projects based in animal models and possibly in a human intervention study that will look at the mechanisms involved and the potential to reverse these adverse effects with adjunct therapies.
5. The potential for opioids and other peptides in the central nervous system to alleviate the mood related effects of endocannabinoid receptor antagonists
Until recently, the endocannabinoid receptor “antagonist”, rimonabant was considered one the brightest hopes for a human anti-obesity therapy. Unfortunately, large scale human trials revealed an adverse effect on mood and a tendency to increase suicide rates. This intolerable adverse effect profile has lead to the removal of the drug but research continues to find ways to preserve the significant positive effects of the drug on weight loss and diabetic status.
This series of experiments looks in animal models at possible adjunct treatments where other compounds, namely opioids and the antagonists of the orexigenic hormone MCH, are co administered with rimonabant in an attempt to circumvent the unwanted effects on mood while preserving or even adding to anorexigenic outcomes.
Honours Positions: Applications and inquiries should be sent to Prof Brian Oldfield (brian.oldfield@monash.edu)
PhD applicants should have a MSc or 1st class Honours.
Current Postgraduate Students
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| Ms Sarah Haas-Lockie PhD Student |
Ms Elaine Adler PhD Student |
Co-Supervised PhD Students:
Nilanka Hertioga
Cathy Jensen
Research Staff
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| Dr Aneta Stefanidis Post Doctoral Fellow |
Dr Aaron Verty Research Fellow |
Dr Juliane Kampe Post Doctoral Fellow |
Ms Erika Salazar-Ortiz Animal Technician |
Current Grants
| NH&MRC Fellowship - Oldfield BJ | (2006-2010) $780,559 |
| NHMRC Project Grant - Oldfield, Prof Brian, Clarke, Prof Iain "The differential innervation of fat - potential to target visceral adiposity" |
(2011-2013) $470,022 |
| NHMRC Project Grant - Watt, A/Prof Matthew, Andrews, Dr Zane, Oldfield, Prof Brian “Physical activity restores energy homeostasis in obesity through hypothalamic neurogenesis” | (2011-2013) $322,524.0 |
| Oldfield BJ, Dixon JB and Brown W - ARC Linkage Grant “Use of an animal model to understand mechanisms underlying reductions in body weight associated with the use of the laparoscopic adjustable gastric band” |
(2010 - 2012) ARC Contribution: 2010 $45,000, 2011 $90,000, 2012 $45,000 Allergan Contribution: Year 1 $146,503, Year 2 $173,660 Total grant funds: $500,163 |
| Oldfield BJ, Dixon JB and Brown W - Alergan Inc. “Use of a rodent model to elucidate the mechanisms underlying weight loss associated with the adjustable gastric band”. |
(2009-2011_ AUS $192,400 |
Recent Key Publications
- Hettigoda NS, Badoer E, McKinley MJ, Oldfield BJ, Allen AM AUTONOMIC COMMAND NEURONS – A NEW INSIGHT INTO NEURONAL ORGANISATION Science (submitted June 2011)
- Verty ANA, Hass-Lockie S, Stefanidis A, Oldfield BJ ANTI-OBESITY EFFECTS OF THE COMBINED ADMINISTRATION OF CB1 RECEPTOR ANTAGONIST RIMONABANT AND MELANIN CONCENTRATING HORMONE ANTAGONIST SNAP-94847 IN DIET INUDCED OBESE MICE. Neuropsychopharmacology (submitted June 2011)
- Haas Lockie S, Czyzyk TA, Chaudhary N, Perez-Tilve1 D, Woods SC, Oldfield BJ, Statnick MA, Tschöp MH. CNS OPIOID SIGNALING SEPARATES CANNABINOID RECEPTOR 1 MEDIATED
- EFFECTS ON BODY WEIGHT AND MOOD-RELATED BEHAVIOR IN MICE Endocrinology (Under second Review with minor revisions June 2011)
- Hübschle T, McAllen RM,. McKinley MJ Oldfield BJ COMPARISON OF THE POLYSYNAPTIC SYMPATHETIC AND PARASYMPATHETIC INNERVATION OF THE RAT SUBMANDIBULAR GLAND Neuroscience (submitted June 2011)
- Kampe J*, Stefanidis A*, Lockie SH, Spencer SJ., Brown WA, Dixon JB, Raven J, Oldfield, BJ (*equal first authors) NEURAL AND HUMORAL MECHANISMS UNDERLYING THE EFFECTIVENESS OF THE ADJUSTABLE GASTRIC BAND – INSIGHTS FROM A RODENT MODEL International Journal of Obesity (under review since May 2011)
- Tsoli1 M, Moore1 M, Burg D, Painter A, Taylor R, Haas- Lockie S, Turner N, Warren A, Cooney G, Oldfield BJ, Clarke S, Robertson G ACTIVATION OF THE THERMOGENIC PROGRAM IN BAT AND DYSREGULATED LIPID METABOLISM IN CANCER CACHEXIA/ANOREXIA SYNDROME IN MICE. Journal of Clinical Investigation (under review since May 2011)
- Verty AN, Evetts MJ, Crouch GJ, McGregor IS, Stefanidis A, Oldfield BJ. THE CANNABINOID RECEPTOR AGONIST THC ATTENUATES WEIGHT LOSS IN A RODENT MODEL OF ACTIVITY-BASED ANOREXIA. Neuropsychopharmacology. 2011 Jun;36(7):1349-58
- Hollis JH, Jonaidi H, Lemus M, Oldfield BJ (2011) THE ENDOCANNABINOID ARACHIDONYLETHANOLAMIDE ATTENUATES ASPECTS OF LIPOPOLYSACCHARIDE-INDUCED CHANGES IN ENERGY INTAKE, ENERGY EXPENDITURE AND HYPOTHALAMIC FOS EXPRESSION. J Neuroimmunol. 2011 Jan 22
- Verty,A.N.A., Evetts,M.J., Crouch,G.J.,McGregor, I.S., Stefanidis,A., Oldfield,B.J.
(Inpress). THE CANNABINOID RECEPTOR AGONIST THC ATTENUATES WEIGHT LOSS IN A RODENT MODEL OF ACTIVITY BASED ANOREXIA. Neuropsychopharmacology (accepted 28 Dec 2010) Impact Factor 6.99. - Jensen CJ, Stankovich J, Butzkueven H, Oldfield BJ, Rubio JP (2010) COMMON VARIATION IN THE MOG GENE INFLUENCES TRANSCRIPT SPLICING IN HUMANS. J Neuroimmunol. 2010 Dec 15;229(1-2):225-31.
