Food and the Brain

Food and the Brain
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Feeding, necessary for survival, is a motivated behaviour and consumption of high-caloric foods even more so. This tendency can be maladaptive. Global development has been accompanied by a new epidemic: obesity. While the problem may stem from overabundance and overconsumption, there is much more to the story than gluttony and inadequate willpower.

The regulation of appetite and feeding relies on many physiological systems. The enteric nervous system innervates the gastrointestinal tract (GIT). It includes the vagal nerve: the conduit between gut and brain for many satiety-signalling molecules. The GIT houses the microbiome, composed of many types of bacteria having; it is significantly involved in digestion. The hypothalamus houses the arcuate, paraventricular and ventrolateral nuclei, all involved in the regulation of feeding. Also located in the hypothalamus is the suprachiasmatic nucleus: the body’s master clock, important in maintaining circadian rhythms relating to, among many other things: sleep and feeding. The ventral tegmental area interacts through dopaminergic circuitry with the hypothalamus and mediates one’s reward response to different foods. Grey matter regions, including the superior frontal gyrus, are involved in inhibitory control of feeding[1]. Circulating hormones are important in relay between these regions. Leptin, manufactured in adipose tissue and ghrelin, in the stomach, are important satiety and hunger signals, respectively. The relative activity of these cortical, endocrine and other regions depends on many factors, some exogenous. Diet-induced epigenetic modification can cause both hypothalamic[2] and dopaminergic[1] neuroanatomical changes. Stress, sleep and mealtime have the capacity to re-entrain circadian clocks in peripheral tissue[4]. Antibiotics and probiotics can affect microbiotic composition. 
Perturbations of this interaction system from abnormal feeding can result in or exacerbate metabolic and affective disorders: obesity-associated pathologies, anorexia nervosa, depression and many others. In understanding the mechanisms underlying normal and abnormal feeding behaviours, we can develop more effective long-term treatments, including anti-obesity drugs.

Bibliography
1. Yokum, S., Hg, J., Stice, E. Relation of regional grey and white matter volumes to current BMI and future increases in BMI: A prospective MRI study. International Journal of Obesity 36, 656-664 (2012).
2. Liu, M. et al. Obesity induced by a high-fat diet downregulates apolipoprotein A-IV gene expression in rat hypothalamus. Am J Physiol Endocrinol Metab 287, E366-E370 (2004).
3. Vucetic, Z., Carlin, J. L., Totoki, K. & Reyes, T. M. Epigenetic dysregulation of the dopamine system in diet-induced obesity. J. Neurochem 120, 891-898 (2012).
4. Stephan, F. K. The ‘Other’ Circadian System: Food as a Zeitgeber. Journal of Biological Rhythms 17, 284–292 (2002).


Anti-Obesity Drugs

main article: Anti-Obesity Drugs
author: Juhie Ahmed

Obesity is on the rise
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Obesity has become a prominent health problem in the last few decades[1]. It can be caused by both genetic and environmental factors; however, its recent increase is mostly attributed to the sedentary lifestyle adopted by much of the population living in industrialized areas [2]. It is associated with comorbidities such as type II diabetes and hypertension, as well as a reduced lifespan [3]. Anti-obesity drugs are an appealing solution to this significant health issue. It is important to remember that while using anti-obesity drugs, optimum weight loss results are achieved when the drugs are paired with a healthier diet and exercise. There are several types of anti-obesity drugs, such as serotonin inhibitors, androgenic drugs, stimulants and inhibitors of fat absorption [4]. Since the early 1900’s anti-obesity drugs have been tied to low efficiency and other serious side effects leading to a discontinuation of a majority of these drugs [4].

Bibliography
1. James PT, Rigby N, Leach R. The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil. 2004;11:3–8.
2. Li M, Cheung BM. Pharmacotherapy for obesity. Br J Clin Pharmacol. 2009;68:804–810.
3. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation.1983;67:968–977.
4. Li, M. F., & Cheung, B. M. (2011). Rise and fall of anti-obesity drugs. World journal of diabetes, 2(2), 19.


Circadian Rhythms: Food, Sleep and Stress

main article: Circadian Rhythms: Food, Sleep and Stress
author: Isabel Mackay-C

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The SCN and other hypothalamic nuclei sync circadian rythms,
like waking and sleeping, to a 24 hour light-dark cycle
ImageSource: Horacio de la Iglesia, fac.org

Located in the hypothalamus is the suprachiasmatic nucleus (SCN): the body’s master clock, which, among other things, governs one’s sleep-wake cycle, secretion of cortisol and core body temperature. It also modulates behavioural states like arousal and feeding. To accomplish this, the SCN projects to other hypothalamic nuclei and communicates and coordinates with many oscillators in peripheral tissue. The lateral hypothalamus and paraventricular nucleus serve as important regions of influence. They communicate with the SCN and other rhythmic systems like the HPA-axis and can elicit motivated behaviours. The activity of neuropeptides in hypothalamic nuclei, namely orexin/hypocretin, is emerging as an important strategy by which the brain maintains energy homeostasis.

While the SCN relies predominantly on photic entrainment, peripheral clocks must be entrained by nonphotic cues. Importantly among them is one’s feeding schedule, which can have dramatic effects on one’s liver, pancreas and other organs.[1] Thus, food-entrainable oscillators (FEOs) are important mechanisms of homeostasis. The discovery of FEOs elucidates the fact that the circadian regulation of hormone secretion and behaviour is reciprocal.
That is: while endogenous oscillators influence behaviour, so too can these oscillators be affected by behaviours
like feeding, sleep duration and stress.[2]

Misalignment in the integration of the SCN and peripheral clocks is associated with a variety of metabolic and affective disorders.
With obesity, major depressive disorder and other pathologies on the rise, it is crucial to understand how one’s temporal habits may
be affecting one’s physiology and, subsequently, one’s health.

Bibliography
1. Schibler, U., Ripperger, J., Brown, S.A. (2003). Peripheral Circadian Oscillators in Mammals: Time and Food. Journal of Biological Rhythms, 18(3), 250–260.
2. Bodosi, B., Gardi, J., Hajdu, I., Szentirmai, E., Obal, F., Jr, & Krueger, J. M. (2004). Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted


Eating Disorders

main article: Eating Disorders
author: Demi Lee

Eating Disorders
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[5]

Eating disorders are characterized as psychiatric disturbances in eating behavior and self-body perception with psychosomatic consequences[1][6]. It is known to carry the highest mortality rate amongst all psychiatric disorders[7]. There are three main classes of eating disorders: anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS)[2]. These disorders predominantly afflict young women but can affect males as well[4]. 

The etiology of eating disorders is currently idiopathic though multifactorial models to understand these disorders and the various genetic, environmental and psychological factors that contribute to their onset are used[1]. It has been hypothesized that the vast amount of change that the body undergoes during puberty increases the vulnerability of the appetite regulation systems and the hypothalamus[3]. In addition, certain types of eating disorders are often associated with certain personality traits[1]. Both AN and BN have high psychiatric comorbidity of depressive symptoms and anxiety disorders like obsessive-compulsive disorder[6].

Bibliography
1. Ahrén, J. C. (2011). Neuropsychological aspects of eating disorders – a focus on diagnostic criteria. In V. R. Preedy et al (Eds.), Handbook of Behavior, Food and Nutrition (pp. 1387-1395). Stockholm, SE: Springer Science.
2. American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev.). doi:10.1176/appi.books.9780890423349 .
3. Connan F., Lightman S. L., Landau S., Wheeler M., Treasure J. A. (2003). Neurodevelopmental model for anorexia nervosa. Physiol Behav, 79, 13–24
4. Carlat, D. J., Camargo, C. A. Jr. (1991). Review of bulimia nervosa in males. Am J Psychiatry, 148(7), 831-843.
5. [Eating Disorders], Retrieved April 1st, 2013, from: http://www.blogilates.com/wp-content/uploads/2012/06/eating-disorder.jpeg.
7. Kaye, W. H., Fudge, J. L., Paulus M. (2009). New insights into symptoms and neurocircuit function of anorexia nervosa. Nature Rev Neurosci, 10, 573–84


Food Addiction

main article: Food Addiction
author: Mohammed Younus

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Obesity is a huge epidemic throughout the world and scientists are tirelessly looking for ways to combat it. Food addiction is as real as drug addiction and has been shown to work largely through the dopamine reward pathway. It has been found that obese people have a decreased amount of dopamine transduction. The hypothalamus is the integration center and receives all the sensory and peripheral signals. It is the job of the hypothalamus to check for the energy status of the body and signal the CNS to engage in feeding behaviour. Lee A. K. et al., (2010)[1] found that 5 genes involved in the transcription of dopamine (DA) were upregulated in the hypothalamus in obese mice. This suggests that obese people are conditioned to eat more, as their hypothalamus is hyperactive. In addition, John & Kenny (2010)[2] found that the striatal dopamine D2 receptors are downregulated in obese rats. This in conjunction with the increased amount of dopamine in the hypothalamus leads to a feed forward cycle. A normal diet does not satisfy the pleasure threshold for an obese person as their reward circuitry is desensitized and requires highly palatable and fatty food on a regular basis to overcome or reach the threshold. The alterations in the dopamine system in both the reward center and the hypothalamus were as a result of epigenetic changes due to high calorie intake[3]. Combating obesity is especially difficult as the feeding behaviour is mediated by multiple peripheral and central mechanisms. There is no single way to combat obesity and has to be tackled at multiple levels.

Bibliography
1. Lee A. K., Mojtahed-Jaberi M., Kyriakou T., Astarloa E. A., Arno M., Marshall N. J., Brain S. D. and O’Dell S. D. (2010) Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus. Nutrition 26, 411–422.
2. Johnson P. M. and Kenny P. J. (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature Neuroscience. 13, 635–641.
3. Vucetic Z, Carlin J.L, Totoki K, Reyes T.M (2012) Epigenetic dysregulation of the dopamine system in diet-induced obesity. Journal of Neurochemistry 120 (6): 891-8.


Food Intake and the Vagus Nerve

main article: Food Intake and the Vagus Nerve
author: Jasmine Chong

Vagus nerve innervation
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The vagus nerve innervates various visceral organs [3]

The vagus nerve (CN X) is tenth among the twelve pairs of cranial nerves. Its projections exchange sensory and motor information with various visceral organ systems. A system of particular interest is the gastrointestinal system, which sends out vagal afferents and mediates the feeling of satiety in response to mechanical and chemical signals from the gut. Abnormal vagal excitability has implications in the lack of voluntary control over food consumption behaviours. Differential vagal activity is involved in satiety thresholds, obesity, and the perpetuation of the binge-purge cycle of bulimia nervosa[1]. Vagus nerve stimulation and vagotomy procedures have been associated with weight loss [2], demonstrating the significance of the vagus nerve in the treatment of obesity.

Bibliography
1. Faris, P. L., Eckert, E. D., Kim, SW., Meller, W. H., Pardo, J. V., Goodale, R. L., & Hartman, B. K. (2006). Evidence of a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms. Journal of Affective Disorders, 92, 79-90.
2. Val-Laillet, D., Biraben, A., Randuineau, G. & Malbert C. H. (2010). Chronic vagus nerve stimulation decreased weight gain, food consumption and sweet craving in adult obese minipigs. Appetite, 55, 245-252.
3. [Vagus Nerve Innervation]. Retrieved March 30, 2013, from: http://healingfromthefreeze.files.wordpress.com/2011/08/vagus.jpg


Genetics of Obesity

main article: Genetics of Obesity
author: Eduard Doumanian

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With rapidly rising urbanization, economic development, and standard of living across the globe, the transition to a first world nation is accompanied by a growing epidemic: Obesity. Ample inexpensive junk food overloaded with sodium, trans and saturated fats, and sucrose abound on every store shelf and attempt to enamor consumers in through advertisements. This preys upon the weaknesses of many individuals, yet there is much more to the story than mere gluttony and insufficient willpower. Some of the upstream causes of insatiable consumption are due to neurological alterations and dysregulation[1]. This includes the hypothalamus (housing the arcuate, paraventricular, and ventromedial nuclei that play a role in food intake regulation), the dopamine (DA) reward system, and the enteric nervous system (with hormonal and neural feedback to the CNS)[1][2]. A multitude of factors can disrupt the homeostasis of the milieu intérieur, thus impacting the metabolic rate and drive to eat. This subtopic is primarily concerned with the genetic causes and epigenetic modifications that initiate and maintain considerable weight gain. Diet-induced downregulation or upregulation of specific genes leads to neuroanatomical changes in the hypothalamic and dopamine systems (which control satiety and reward, respectively)[1][2]. Monogenetic causes of obesity will be explored, as well as the potential remedies through behaviour (e.g. exercise) and genetic engineering.

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Bibliography
1. Vucetic, Z., Carlin, J. L., Totoki, K., & Reyes, T. M. (2012). Epigenetic dysregulation of the dopamine system in diet-induced obesity. Journal of Neurochemistry, 120, 891-898. doi: 10.1111/j.1471-4159.2012.07649.x
2. MacKay, W. A. (2010). NEURO 101: Neurophysiology without tears . Toronto: Sefalotek Ltd.


Hormonal Regulation of Feeding Behaviour

main article: Hormonal Regulation of Feeding Behaviour
author: Joonyoung Hwang
The human body is normally capable of matching the day-to-day fluctuations in energy intake with an appropriate amount of energy expenditure. This homeostatic regulation of energy consumption is achieved by many peptides and steroids that circulate in the body, imposing substantial influence on development, appetite, and feeding behaviour. These signalling molecules, or hormones, are largely regulated and secreted from the hypothalamus, pancreas, fat cells, and the gastrointestinal tract.

The actions and mechanisms in which these hormones regulate our appetite and feeding behaviour through signalling pathways involving the leptin-melanocortin pathway in the ventromedial hypothalamus and other downstream signalling effects of leptin are extremely salient to metabolic homeostasis. In addition, gut and endocrine organ derived hormones such as ghrelin, cholecystokinin (CCK) and peptide YY3-36 (PYY3-36) have significant effects on feeding behaviour and appetite.

Recent discoveries have suggested that some of these hormones, markedly leptin and ghrelin, have additional effects on the cognitive aspects of the nervous system such as stress and depressive symptoms. Specifically, leptin and ghrelin have recently been suggested as potential pharmaceutical targets of anti-anxiety and anti-depressant drugs, as these molecules are associated with decreased levels of depressive symptoms and chronic stress in human adults[1] and mouse models[2].

Therefore, the overall effects of hormones on feeding behavior and energy consumption require thorough investigation, with further emphasis on newly discovered cognitive impacts of these hormones on stress and depression.

Obesity
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Obesity is in part caused by disturbances in hormonal regulation of energy homeostasis. Image source:[3]
Bibliography
1. Lawson, E. A., Miller, K. K., Blum, J. I., Meenaghan, E., Misra, M., Eddy, K. T., Herzog, D. B., & Klibanski, A. (2012). Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat. Clinical Endocrinology, 76(4), 520-525.
2. Lutter, M., Sakata, I., Osborne-Lawrence, S., Rovinsky, S.A., Anderson, J.G., Jung, S., Birnsbaum, S., Yanagisawa, M., Elmquist, J.K., Nestler, E.J., Zignman, J.M. (2008). The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nature Neuroscience, 11(7), 752-753.
3. [Obesity Silhouette]. Retrievd March 25, 2013, from: http://fittipdaily.com/wp-content/uploads/2010/06/USA-Obesity-Rate.jpg


Inhibitory Brain Circuitry and Food Intake

main article: Inhibitory Brain Circuitry and Food Intake
author: bertoiaj

Introduction

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The Well-Stocked Kitchen - Joachim Beuckelaer (circa 1533–1575)
Image source: http://commons.wikimedia.org/wiki/File:Joachim_Beuckelaer_003.jpg

Evolutionary perspectives of the current obesity epidemic suggest that the overconsumption of food in modern society is the consequence of our formerly adaptive behaviour to overeat when the supply was available [1] . This evolved overeating behaviour would help to ensure one would be sufficiently sustained during periods when food was scarce [1]. However, the conditions of the industrialized world now provide an overabundance of food that makes this proposed inherent drive to overeat and underdeveloped inhibitory control of food intake maladaptive [1]. The neurobiological differences between individuals that are able to effectively control their food intake in an environment that provides an excessive food supply and individuals who are overweight as a result of lacking dietary self-constraint has important implications for understanding obesity and its possible risk factors [2]. Moreover, the investigation of the neural mechanisms behind the inhibitory control of food intake has been proposed as a critical area of research for methods of prevention and treatment of obesity [2]. Findings from both functional and structural neuroimaging studies have been key in analyzing the differences in brain regions that control food intake between obese and non-obese individuals. Specific areas of research include what areas of the brain are activated during self restraint from eating [3] and the structural brain differences between those of normal and high BMIs such as grey matter regions involved in inhibitory control and white matter regions implicated in food cues and reward [4].

Bibliography
1. King, B.M. The modern obesity epidemic, ancestral hunter-gatherers, and the sensory/reward control of food intake. Am Psychol, 2, 88-96 (2013).
2. Moran, T.H., & Westerterp-Plantenga, M. The potential role and deficits in frontal cortical brain areas implicated in the executive control of food intake. International Journal of Obesity, 36, 625-626 (2012).
3. Hollmann, M., Hellrung, L., Pleger, B., Schlogl, H., Kabisch, S., Stumvoll, M., Villringer, A., & Horstmann, A. Neural correlates of the volitional regulation of the desire for food. International Journal of Obesity, 36, 648-655 (2012).
4. Yokum, S., Hg, J., & Stice, E. Relation of regional grey and white matter volumes to current BMI and future increases in BMI: A prospective MRI study. International Journal of Obesity, 36, 656-664 (2012).


Microbiome

main article: Microbiome
author: Jamie Hlusko

Microbiome
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More than 500 species of bacteria live in an individual’s digestive tract (hereafter referred to as the gut), although most of the bacteria come from about 30 or 40 species.1 Since bacterial cells are so much smaller than our eukaryotic cells and do not require the support of our extensive connective tissue, we can house ten times as many bacterial cells in our gut (10^14) than we have human cells in the rest of our body.2 Functions of gut bacteria include digesting our food, stimulating cell growth and repressing the growth of harmful microorganisms.3 Our microbiota also have cognitive effects. It has been known for centuries than syphilitic infection (with the bacteria Treponema pallidum) can cause psychological symptoms. This “syphilitic madness” is now better characterized as causing depression, confusion, irritability, poor concentration, dementia and ultimately death without treatment.4 Another pathogenic bacteria is Toxoplasma gondii which reproduces in cats but can live and cause psychiatric effects in humans. In immunocompromised patients T. gondii infection can lead to death by brain inflammation however for most people an infection is asymptomatic. Around 10% of Americans are estimated to be infected with T. gondii,5 although the rate is higher among people with schizophrenia6 and personality disorders.7 Infection is associated with higher rates of car crashes,8 and violent suicidal behaviour.9 Negative effects (including cognitive effects) of the microbiome are not limited to pathogenic bacteria, changing the proportion of bacterial species present in healthy populations can result in intestinal disorders, metabolic disorders such as obesity and diabetes as well as psychiatric disorders such as depression and anxiety.




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