Our research focuses on identifying neuronal pathways in the central regulation of energy homeostasis and, when that regulation goes wrong, obesity-induced hypertension.

Specialized brain structures, including the hypothalamus, sense the body´s energy status, integrate this information and elicit an appropriate response to the rest of the body. Recent research has begun to unravel some of the neuronal pathways regulating body weight, but the exact mechanisms by which metabolic signals are sensed by the CNS and translated into a coordinated response are still unclear.

Genome wide association scans in patient populations are identifying more and more novel genes associated with the dysregulation of body weight, food intake and glucose homeostasis, but often the physiological function and how these genes might fit into the pathways leading to disease remain unclear. Using genetic modification techniques, we investigate the physiological contribution of these genes in subsets of neurons to the control of metabolic balance. In other words, we make manipulations at the molecular level (for example in a hypothalamic signalling cascade) and combine this with systems level physiological analysis (such as the analysis of body weight and glucose homeostasis).

Ultimately this research enables us to better understand the mechanisms involved in maintaining metabolic balance.

Although we know that the hypothalamus is one of the key CNS areas sensing and integrating information on body nutrient state, the molecular mechanisms translating hypothalamic nutrient-sensing into changes in gene expression and ultimately adjustment of neuronal function remain poorly defined. Furthermore, the specific physiological functions encoded by these dynamically modulated transcriptional programs (transcriptomes) are unclear.  We have recently identified a novel transcriptional co-activator, CRTC2, as an important link between neuronal glucose-sensing and the dynamic regulation of a specific transcriptome (Lerner et. al., 2009, EMBO Reports).

Homing in on neurons themselves, a fascinating aspect of brain performance is how the intra-cellular energy state affects neuronal function, health and longevity. Decline in memory performance is closely related to, for example, age-mediated structural and functional changes of neurons leading to loss of synaptic function (and thus neuron-to-neuron communication). Synaptic performance is critically dependent on robust supply of energy in the form of ATP for neurons’ metabolically very expensive processes. We are currently investigating how CNS genes affected by whole body metabolic state might integrate this information with adjustment of neuronal health and synaptic function.

Recent research has demonstrated that agents increasing or decreasing food intake have associated effects on the cardiovascular system; a highly undesirable effect in the design of future body weight reducing therapies. Using genetic modification techniques in combination with radio-telemetry to measure cardiovascular function, we investigate how CNS genes important in the regulation of food intake also affect the cardiovascular system.

Please see also: http://www.bristol.ac.uk/phys-pharm/people/nina-balthasar/index.html

5 Selected Publications

Sohn JW., Harris LE., Berglund ED., Liu T., Vong L., Lowell BB., Balthasar N., Williams KW., Elmquist JK. (2013) Melanocortin 4 Receptors Reciprocally Regulate Sympathetic and Parasympathetic -Preganglionic Neurons. Cell, 152(3): 612-9.
 
Weir HJM., Murray TK., Kehoe PG., Love S., Verdin EM., O’Neill MJ., Lane JD., Balthasar N. (2012). CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer’s disease. PLOSOne, 7(11): e48225.
 
Rossi J., Balthasar N., Olson D., Scott M., Berglund E., Lee CE., Choi MJ., Lauzon D., Lowell BB., Elmquist JK. (2011) Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab., 13(2): 195-204.
 
Lerner RG., Depatie C., Rutter GA., Screaton RA., Balthasar N. (2009). Hypothalamic CRTC2 Links Glucose Sensing with cAMP-reponse-element-mediated Gene Transcription. EMBO Rep., 10(10): 1175-81.
 
Balthasar N. (2009) Feeding Signals to the Hungry Mind. Exp. Physiol., 94(8): 857-66. 

Awards, Fellowships and Honours

2008            Physiological Society GL Brown Prize Lecture
2007            Lister Institute Research Prize
2007            RCUK Academic Research Fellowship
2006            British Heart Foundation Intermediate Research Fellowship
2005            American Heart Association Scientist Development Grant
2005            Keystone Symposia Scholarship
2003            American Diabetes Association and European Association for the Study of Diabetes Trans-Atlantic Fellowship
2000            The Wellcome Trust International Prize Fellowship

• CNS Regulation of Energy Homeostasis
• CNS Regulation of Obesity-Induced Hypertension
• Generation and Metabolic Analysis of Neuronal Subset-Specific Genetically-Modified Mice
• CNS Transcriptome Regulation in Obesity
• Intracellular Energy Homeostasis in Ageing and Age-Associated Neuropathology