Prof Brian Oldfield - Researcher Profile

Brian Oldfield

Address

Department of Physiology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

Bariatric surgery addressing large problems

Sixty-one per cent of Australians are overweight or obese, and despite countless fad diets and apparent quick-fix solutions, this figure is on the rise. Bariatric surgery is the only available clinical treatment for obesity. Professor Brian Oldfield wants to understand why lap band surgery -- the simplest form of bariatric surgery -- has such a strong influence on our stomach-to-brain interactions.

 

The two most common types of bariatric surgery are the adjustable gastric band, or lap band, and Roux-en-Y gastric bypass. In Australia, more than 80 per cent of procedures involve the adjustable gastric band, which doctors inflate according to the patient’s needs. Brian believes bariatric surgery is a viable option for obese people if dieting and other lifestyle changes have failed.

“If you look at the figures on the impact of different interventions or strategies, people can lose five per cent of their body weight by changing their diet and exercise regime, sometimes more,” says Brian. “But if you look at those people over eight or 10 years, virtually all of them return to their original weight. That’s because we have a genetic environment in our bodies that drives us to maintain body fat.

“Whatever breed of bariatric surgery you want to talk about, patients lose at least 25 to 30 per cent of their body weight and 60 to 70 per cent of their excess body weight.”

Brian says the adjustable gastric band has advantages over the more complex Roux-en-Y procedure that dominates bariatric surgery in the United States. He says the importance lies not in the band itself, but in the chemical reactions it creates.

“Initially, everybody thought people ate less with a gastric band fitted because it was restrictive. It just stopped the food getting in so you couldn’t eat as much. It doesn’t work like that. We are charged with finding out the mechanism of the effectiveness of the adjustable gastric band." 

Brian believes a better understanding of why the band works could eliminate the need for surgery altogether.

“Knowing why the band works is important because it can change the way you do bariatric surgery,” he says. “It can give you confidence and you can market it better. But the real impact is if you understand the stomach-to-brain interactions that can cause satiety or eliminate diabetes, we can actually bypass bariatric surgery. That’s the major long-term driver.” 

Brian is also working on a project involving lipolysis, the process whereby the nervous system breaks down body fat. By tracking a mutated form of Pseudorabies virus through the nervous system, Brian is hoping to increase lipolysis preferentially. He says this could lead to a reduction in abdominal fat which, unlike subcutaneous fat, relates to issues like cardiovascular disease and diabetes.

“We thought there may be some differential input from the nervous system to subcutaneous fat and abdominal fat, and that in some way the brain controls these differently,” he says. "Given that the activity of brain pathways is mediated by neurotransmitters, it could be possible to modulate the activity of the pathways that were going to abdominal fat.

“The advantage we have is a Pseudorabies virus that glows red and a Pseudorabies virus that glows green. You can inject the green virus into the subcutaneous fat and the red virus into abdominal fat, follow their passage through the nervous system and map the pathways that are controlling subcutaneous or abdominal fat. So you can start to investigate the changes in genes in specific nerve cells that are related to one type of fat or the other.” 

 

Qualifications

BACHELOR OF SCIENCE
Institution: Monash University
Year awarded: 2007
PHD IN PHYSIOLOGY & MEDICINE
Institution: Monash University
Year awarded: 2007

Publications

Books

McKinley, M.J., McAllen, R.M., Davern, P., Giles, M.E., Penschow, J., Sunn, N., Uschakov, A., Oldfield, B.J., 2003, The sensory circumventricular organs of the mammalian brain, Springer-Verlag Berlin, USA.

Book Chapters

McKinley, M.J., Oldfield, B.J., 2008, Angiotensin II, in Encyclopedia of Neuroscience, eds LR Squire, Elsevier Ltd, UK, pp. 389-395.

McKinley, M.J., Allen, A.M., Oldfield, B.J., 2008, Angiotensin actions on and within brain, in Encyclopedia of Neuroscience, eds LR Squire, Elsevier Ltd, UK, pp. 381-388.

McKinley, M.J., Clarke, I.J., Oldfield, B.J., 2004, Circumventricular Organs, in The Human Nervous System, eds G Paxinos & JK Mai, Elsevier Academic Press, USA, pp. 562-591.

Journal Articles

Verty, A.N.A., Lockie, S.K.H., Stefanidis, A., Oldfield, B.J., 2013, Anti-obesity effects of the combined administration of CB1 receptor antagonist rimonabant and melanin-concentrating hormone antagonist SNAP-94847 in diet-inudced obese mice, International Journal Of Obesity [P], vol 37, issue 2, Nature Publishing Group, UK, pp. 279-287.

Tsoli, M., Moore, M., Burg, D., Painter, A., Taylor, R., Lockie, S.K.H., Turner, N., Warren, A., Cooney, G.J., Oldfield, B.J., Clarke, S., Robertson, G., 2012, Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice, Cancer Research [P], vol 72, issue 17, American Association for Cancer Research, USA, pp. 4372-4382.

Lockie, S.K., Heppner, K.M., Chaudhary, N., Chabenne, J.R., Morgan, D.A., Veyrat-Durebex, C., Ananthakrishnan, G., Rohner-Jeanrenaud, F., Drucker, D.J., DiMarchi, R., Rahmouni, K., Oldfield, B.J., Tschop, M.H., Perez-Tilve, D., 2012, Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling, Diabetes [P], vol 61, issue 11, American Diabetes Association, USA, pp. 2753-2762.

Clarke, I.J., Smith, J.T., Henry, B.A., Oldfield, B.J., Stefanidis, A., Millar, R.P., Puspita Sari, I., Chng, K., Fabre-Nys, C., Caraty, A., Ang, B., Chan, L., Fraley, G.S., 2012, Gonadotropin-inhibitory hormone is a hypothalamic peptide that provides a molecular switch between reproduction and feeding, Neuroendocrinology [P], vol 95, issue 4, S. Karger AG, Switzerland, pp. 305-316.

Kampe, J., Stefanidis, A., Lockie, S.K.H., Brown, W.A., Dixon, J., Odoi, A., Spencer, S.J., Raven, J., Oldfield, B.J., 2012, Neural and humoral changes associated with the adjustable gastric band: insights from a rodent model, International Journal Of Obesity [P], vol 36, issue 11, Nature Publishing Group, United Kingdom, pp. 1403-1411.

Adler, E.S., Hollis, J.H., Clarke, I.J., Grattan, D.R., Oldfield, B.J., 2012, Neurochemical characterization and sexual dimorphism of projections from the brain to abdominal and subcutaneous white adipose tissue in the rat, Journal Of Neuroscience [P], vol 32, issue 45, Society for Neurosciences, USA, pp. 15913-15921.

Lockie, S.K.H., Czyzyk, T.A., Chaudhary, N., Perez-Tilve, D., Woods, S.C., Oldfield, B.J., Statnick, M.A., Tschop, M.H., 2011, CNS opioid signaling separates cannabinoid receptor 1-mediated effects on body weight and mood-related behavior in mice, Endocrinology [P], vol 152, issue 10, The Endocrine Society, USA, pp. 3661-3667.

Lim, K., Armitage, J., Stefanidis, A., Oldfield, B., Black, M., 2011, IUGR in the absence of postnatal "catch-up" growth leads to improved whole body insulin sensitivity in rat offspring, Pediatric Research [P], vol 70, issue 4, Nature Publishing Group, USA, pp. 339-344.

Verty, A., Evetts, M., Crouch, G., McGregor, I., Stefanidis, A., Oldfield, B., 2011, The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia, Neuropsychopharmacology [P], vol 36, issue 7, Nature Publishing Group, UK, pp. 1349-1358.

Hollis, J.H., Jonaidi, H., Lemus, M.B., Oldfield, B.J., 2011, The endocannabinoid arachidonylethanolamide attenuates aspects of lipopolysaccharide-induced changes in energy intake, energy expenditure and hypothalamic Fos expression, Journal of Neuroimmunology [P], vol 233, issue 1-2, Elsevier BV, The Netherlands, pp. 127-134.

Tschop, J., Nogueiras, R., Lockie, S.K.H., Kasten, K.R., Castaneda, T.R., Huber, N., Guanciale, K., Perez-Tilve, D., Habegger, K., Ottaway, N., Woods, S.C., Oldfield, B., Clarke, I., Chua Jr, S., Farooqi, I.S., O'Rahilly, S., Caldwell, C.C., Tschop, M.H., 2010, CNS leptin action modulates immune response and survival in sepsis, Journal Of Neuroscience [P], vol 30, issue 17, Society for Neuroscience, USA, pp. 6036-6047.

Hollis, J.H., Lemus, M.B., Evetts, M.J., Oldfield, B.J., 2010, Central interleukin-10 attenuates lipopolysaccharide-induced changes in food intake, energy expenditure and hypothalamic Fos expression, Neuropharmacology [P], vol 58, issue 4-5, Pergamon, UK, pp. 730-738.

Chen, D., Hazelwood, L., Walker, L.L., Oldfield, B.J., McKinley, M.J., Allen, A.M., 2010, Changes in angiotensin type 1 receptor binding and angiotensin-induced pressor responses in the rostral ventrolateral medulla of angiotensinogen knockout mice, American Journal Of Physiology-Regulatory Integrat..., vol 298, American Physiological Society, USA, pp. R411-R418.

Jensen, C.J., Stankovich, J., Butzkueven, H., Oldfield, B.J., Rubio, J.P., 2010, Common variation in the MOG gene influences transcript splicing in humans, Journal of Neuroimmunology [P], vol 229, issue 1-2, Elsevier BV, The Netherlands, pp. 225-231.

Qi, Y., Henry, B.A., Oldfield, B.J., Clarke, I.J., 2010, The action of leptin on appetite-regulating cells in the ovine hypothalamus: Demonstration of direct action in the absence of the arcuate nucleus, Endocrinology [P], vol 151, issue 5, The Endocrine Society, USA, pp. 2106-2116.

Verty, A.N., Allen, A.M., Oldfield, B.J., 2010, The endogenous actions of hypothalamic peptides on brown adipose tissue thermogenesis in the rat, Endocrinology [P], vol 151, issue 9, The Endocrine Society, USA, pp. 4236-4246.

Kampe, J., Brown, W.A., Stefanidis, A., Dixon, J., Oldfield, B.J., 2009, A rodent model of adjustable gastric band surgery-implications for the understanding of underlying mechanisms, Obesity Surgery, vol 19, Springer New York LLC, USA, pp. 625-631.

Kampe, J., Tschop, M.H., Hollis, J.H., Oldfield, B.J., 2009, An anatomic basis for the communication of hypothalamic, cortical and mesolimbic circuitry in the regulation of energy balance, European Journal Of Neuroscience [P], vol 30, issue 3, Wiley-Blackwell Publishing Ltd, UK, pp. 415-430.

Ootsuka, Y., de Menezes, R.C., Zaretsky, D.V., Alimoradian, A., Hunt, J., Stefanidis, A., Oldfield, B.J., Blessing, W.W., 2009, Brown adipose tissue thermogenesis heats brain and body as part of the brain-coordinated ultradian basic rest-activity cycle, Neuroscience [P], vol 164, issue 2, Pergamon, UK , France, pp. 849-861.

Qi, Y., Namavar, M.R., Iqbal, J., Oldfield, B.J., Clarke, I.J., 2009, Characterization of the projections to the hypothalamic paraventricular and periventricular nuclei in the female sheep brain, using retrograde tracing and immunohistochemistry, Neuroendocrinology [P], vol 90, issue 1, S. Karger AG, Switzerland, pp. 31-53.

Verty, A., Boon, W.M., Mallet, P.E., McGregor, I.S., Oldfield, B.J., 2009, Involvement of hypothalamic peptides in the anorectic action of the CB 1 receptor antagonist rimonabant (SR 141716), European Journal Of Neuroscience [P], vol 29, issue 11, Wiley-Blackwell Publishing Ltd, UK, pp. 2207-2216.

Qi, Y., Oldfield, B.J., Clarke, I.J., 2009, Projections of RFamide-related peptide-3 neurones in the ovine hypothalamus, with special reference to regions regulating energy balance and reproduction, Journal of Neuroendocrinology [P], vol 21, issue 8, Wiley-Blackwell Publishing Ltd, UK, USA, pp. 690-697.

Jensen, C.J., Oldfield, B.J., Rubio, J.P., 2009, Splicing, cis genetic variation and disease, Biochemical Society Transactions [P], vol 37, issue Pt. 6, Portland Press Ltd, UK, pp. 1311-1315.

Verty, A., Allen, A.M., Oldfield, B.J., 2009, The effects of rimonabant on brown adipose tissue in rat: Implications for energy expenditure, Obesity [P], vol 17, issue 2, Nature Publishing Group, USA, pp. 254-261.

Stefanidis, A., Verty, A., Allen, A.M., Owens, N.C., Cowley, M.A., Oldfield, B.J., 2009, The role of thermogenesis in antipsychotic drug-induced weight gain, Obesity, vol 17, Nature Publishing Group, USA, pp. 16-24.

McKinley, M.J., Walker, L.L., Alexiou, T., Allen, A., Campbell, D.J., Di Nicolantonio, R., Oldfield, B.J., Denton, D.A., 2008, Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin, American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol 294, issue 5, American Physiological Society, USA, pp. R1533-R1543.

Hollis, J.H., McKinley, M.J., Lemus, M.B., Kampe, J., Oldfield, B.J., 2008, The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex: a neuroanatomical framework for the generation of thirst, American Journal of Physiology - Regulatory Integrative Comparative Physiology, vol 294, issue 4, American Physiological Society, USA, pp. R1390-R1401.

Oldfield, B.J., Allen, A.M., Davern, P., Giles, M.E., Owens, N.C., 2007, Lateral hypothalamic 'command neurons' with axonal projections to regions involved in both feeding and thermogenesis, European Journal of Neuroscience, vol 25, issue 8, Blackwell Publishing, Oxford England UK, pp. 2404-2412.

Qi, Y., Iqbal, J., Oldfield, B.J., Clarke, I.J., 2007, Neural connectivity in the mediobasal hypothalamus of the sheep brain, Neuroendocrinology, vol 87, Karger, Basel, Switzerland, pp. 91-112.

Kampe, J., Wiedmer, P., Pfluger, P.T., Castaneda, T.R., Burget, L., Mondala, H., Kerr, J., Liaw, C., Oldfield, B.J., Tschop, M.H., Bagnol, D., 2006, Effect of central administration of QRFP(26) peptide on energy balance and characterization of a second QRFP receptor in rat, Brain Research, vol 1119, Elsevier Science, Amsterdam Netherlands, pp. 133-149.

Lawrence, A.J., Cowen, M., Yang, H., Chen, F., Oldfield, B.J., 2006, The orexin system regulates alcohol-seeking in rats, British Journal of Pharmacology, vol 148, issue 6, Nature Publishing Group, London England, pp. 752-759.

McKinley, M.J., Denton, D.A., Oldfield, B.J., De Oliveira, L.B., Mathai, M.L., 2006, Water intake and the neural correlates of the consciousness of thirst, Seminars in Nephrology [P], vol 26, issue 3, WB Saunders Co., USA, pp. 249-257.

Montanaro, M.S., Allen, A.M., Oldfield, B.J., 2005, Structural and functional evidence supporting a role for leptin in central neural pathways influencing blood pressure in rats, Experimental Physiology, vol 90, issue 5, Blackwell Publishing, Oxford UK, pp. 689-696.

McKinley, M.J., Cairns, M.J., Denton, D.A., Egan, G.F., Mathai, M.L., Uschakov, A., Wade, J.D., Weisinger, R.S., Oldfield, B.J., 2004, Physiological and pathophysiological influences on thirst, Physiology and Behavior [P], vol 81, issue 5, Elsevier Inc., USA, pp. 795-803.

McKinley, M.J., Mathai, M.L., McAllen, R.M., McClear, R.C., Miselis, R.R., Pennington, G.L., Vivas, L., Wade, J.D., Oldfield, B.J., 2004, Vasopressin secretion: Osmotic and hormonal regulation by the lamina terminalis, Journal of Neuroendocrinology [P], vol 16, issue 4, Wiley-Blackwell Publishing Ltd, UK, The Netherlands, USA, pp. 340-347.

Sunn, N., McKinley, M.J., Oldfield, B.J., 2003, Circulating angiotensin II activates neurones in circumventricular organs of the lamina terminalis that project to the bed nucleus of the stria terminalis, Journal of Neuroendocrinology [P], vol 15, issue 8, Wiley-Blackwell Publishing Ltd, UK, The Netherlands, USA, pp. 725-731.

McKinley, M.J., Albiston, A.L., Allen, A.M., Mathai, M.L., May, C.N., McAllen, R.M., Oldfield, B.J., Mendelsohn, F.A., Chai, S.Y., 2003, The brain renin-angiotensin system: location and physiological roles, International Journal of Biochemistry and Cell Biology [P], vol 35, issue 6, Pergamon, UK, pp. 901-918.

Sinnayah, P., Blair-West, J.R., McBurnie, M., McKinley, M.J., Oldfield, B.J., Rivier, J., Vale, W.W., Walker, L.L., Weisinger, R.S., Denton, D.A., 2003, The effect of urocortin on ingestive behaviours and brain Fos immunoreactivity in mice, European Journal Of Neuroscience [P], vol 18, issue 2, Wiley-Blackwell Publishing Ltd, UK, Germany, pp. 373-382.

Sunn, N., Egli, M., Burazin, T.C., Burns, P., Colvill, L., Davern, P., Denton, D.A., Oldfield, B.J., Weisinger, R.S., Rauch, M., Schmid, H.A., McKinley, M.J., 2002, Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat, Proceeding of the National Academy of Science USA, vol 99, issue 3, National Academy of Sciences, USA, pp. 1701-1706.

Oldfield, B.J., Giles, M.E., Watson, A., Anderson, C., Colvill, L.M., McKinley, M.J., 2002, The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat, Neuroscience, vol 110, issue 3, Elsevier Science Ltd, Oxford United Kingdom, pp. 515-526.

Wilson, Y., Nag, N., Davern, P., Oldfield, B.J., McKinley, M.J., Greferath, U., Murphy, M., 2002, Visualization of functionally activated circuitry in the brain, Proceedings of the National Academy of Science, vol 99, issue 5, National Academy of Sciences, USA, pp. 3252-3257.

Sly, D.J., McKinley, M.J., Oldfield, B.J., 2001, Activation of kidney-directed neurons in the lamina terminalis by alterations in body fluid balance, American Journal of Physiology Regulatory Intergrative Comp Physiology, vol 281, American Physiological Society, Bethesda USA, pp. 1637-1646.

Oldfield, B.J., Davern, P.J., Giles, M.E., Allen, A.M., Badoer, E., McKinley, M.J., 2001, Efferent neural projections of angiotensin receptor (AT1) expressing neurones in the hypothalamic paraventricular nucleus of the rat, Journal of Neuroendocrinology, vol 13, Blackwell Publishing, Oxford England, pp. 139-146.

Weisinger, R.S., Burns, P., Colvill, L.M., Davern, P.J., Giles, M.E., Oldfield, B.J., McKinley, M.J., 2000, FOS immunoreactivity in the lamina terminalis of adrenalectomized rats and effects of angiontension II Type I receptor blockade or deoxycorticosterone, Neuroscience, vol 98, Pergamon-Elsevier Science Ltd, Oxford United Kingdom, pp. 167-180.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Adjustable Gastric Band (AGB) surgery, an animal model.
Supervisors:
Oldfield, B (Main), Stefanidis, A (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Lipid Metabolism in the CNS: implications for peripheral metabolism.
Supervisors:
Watt, M (Main), Andrews, Z (Associate), Oldfield, B (Associate).
Program of Study:
(MASTER'S BY RESEARCH).
Thesis Title:
Mechanisms Underlying the Efficacy of the AGB, a Neural Perspective.
Supervisors:
Oldfield, B (Main), Stefanidis, A (Associate).

Completed Supervision

Student:
Briggs, D.
Program of Study:
Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. (PHD) 2012.
Supervisors:
Andrews, Z (Main), Oldfield, B (Associate).
Student:
Forrest, N.
Program of Study:
Adjustable Gastric Banding. 2011.
Supervisors:
Oldfield, B (Main).
Student:
Haas Lockie, S.
Program of Study:
Modes of action of obesity therapeutics: investigation and modulation of the cannabinoid 1, opioid and GLP-1 receptors as targets for treating metabolic disease. (PHD) 2012.
Supervisors:
Oldfield, B (Main).
Student:
Jensen, C.
Program of Study:
Exploring genetic variation in multiple sclerosis. (PHD) 2011.
Supervisors:
Oldfield, B (Main).
Student:
Jensen, C.
Program of Study:
GENETIC AND FUNCTIONAL CHARACTERISATION OF A MURINE MODEL OF OBESITY. 2006.
Supervisors:
Oldfield, B (Joint-Co).
Student:
Kampe, J.
Program of Study:
The involvement of the Central Nervous System in the control of food intake and obesity-from the gut to the cerebral cortex. (PHD) 2009.
Supervisors:
Oldfield, B (Main).
Student:
Qi, Y.
Program of Study:
A study of neural pathways in the ovine hypothalamus that control food intake and energy expenditure. (PHD) 2009.
Supervisors:
Clarke, I (Main), Oldfield, B (Associate).
Student:
Stefanidis, A.
Program of Study:
Toward an understanding of antipsychotic drug induced weight gain - use of a rodent model. (PHD) 2010.
Supervisors:
Oldfield, B (Main).