By Josee Beaudry

You may be that person who struggles to lose those last few pounds, or you keep gaining weight despite your best efforts, or maybe you can’t seem to keep any weight on. This is pretty normal. However, there are extreme cases; cases such as severe obesity or anorexia nervosa. These cases may be so severe that a person’s weight becomes their handicap and it is impossible to change it without some outside help. This is where Dr. Alfonso Abizaid’s research comes into play.

Dr. Abizaid is an Associate Professor at ĐÓ°ÉÔ­´´ University and he looks at how the brain controls how much energy an individual needs to take in to survive and how much energy is spent on food seeking behaviors. He not only studies the processes associated with energy regulation but also looks at behavioral aspects such as how one acts when experiencing cravings or how these cravings are affected during certain stressful situations. He is particularly interested in when these regulatory processes don’t work properly and how pathological problems such as obesity or wasting diseases occur. When regulatory processes aren’t functioning normally one can have issues associated with both ends of the spectrum. For example, an individual may have energy regulatory problems that cause weight gain and severe obesity or they may experience serious metabolic or psychological disorders that lead to severe malnutrition and wasting. Dr. Abizaid’s goal is to seek treatments that may help such individuals. If it is possible to pinpoint exactly how things go wrong in energy regulation, then it may be possible to help people lose weight or gain weight depending on their case.

One emphasis of his research has been on the hormone ghrelin, which regulates food intake and metabolism. What makes this hormone so interesting is that it is produced by the gut and makes people eat while most hormones in the gut reduce food intake. Ghrelin facilitates the accumulation of body fat and if released during a long period of time it leads to weight gain. Even more interestingly, ghrelin levels rise when an individual is stressed. Consequently, this may be the reason why people may tend to eat more and gain weight during stressful times.

Dr. Abizaid’s interest in ghrelin began while he was a postdoctoral fellow at Yale University. What really peeked his interest in ghrelin was where the hormone was acting in the brain. Of particular interest was that receptors for ghrelin were not only found in the hypothalamus- an area of the brain that works like a thermostat for energy in the brain, but also found in other areas of the brain including the ventral tegmental area (VTA). The VTA is a brain region associated with reward and addiction. That fact that ghrelin receptors were found in this area suggested that, in addition to food intake and energy regulation, this hormone could be implicated in psychological processes such as motivation, emotion and memory. Indeed, in reality we don’t just eat because we are out of energy stores. Most of the time we eat in response to signals that evoke previous pleasurable experiences with certain foods, or in response to time cues that tell us when foods are available. The fact that ghrelin targets and stimulates brain regions like the VTA also indicates that ghrelin may be a substrate for what we know as “cravings”.

Recently, Abizaid along with his students, discovered a drug that decreases the active form of the ghrelin hormone. While this drug reduces weight gain and body fat it does not seem to cause any obvious side effects in preclinical studies. Despite this exciting discovery, they still do not know the specific mechanism in which the new drug deactivates ghrelin and for this reason they cannot test it on humans until they have a better understanding of how this drug works. Dr. Abizaid has been on the forefront of energy regulation and great discoveries lay ahead. ĐÓ°ÉÔ­´´ University is lucky to have such an innovative researcher!

.

, from the Dept. of Biology, was the recipient of a CIHR New Investigators Salary Award to support his research on antibiotic resistance and bacterial adaptation. While antibiotics have been used for decades to fight bacterial infection, the evolution of antibiotic resistance has emerged as a critical public health threat. In this research, Wong will study the evolution and genetics of antibiotic resistance, and of pathogen adaptation more generally. He will use laboratory and clinical populations of infectious bacteria, including E. coli and bovine tuberculosis, to identify mutations that confer resistance or that contribute to increased fitness during infection. In addition, he has developed an innovative genetic screen that will enable him to identify novel therapeutics targeted towards antibiotic resistant pathogens.

, from the Dept.  of Neuroscience, received funding to better understand the hormonal mechanisms by which stress responses alter behavioral and metabolic processes associated with obesity. Obesity is related to a variety of pathologic conditions that include cancer, heart disease, diabetes, and renal insufficiency, all of which can lead to an early death and poor quality of life. While it is clear that there are genetic factors that are closely associated with obesity, environmental factors also play an important role. Stress, for example has been associated with a number of metabolic changes that ultimately can lead to obesity, insulin resistance, and cardiovascular disease. Interestingly, a number of symptoms that are seen following exposure to different types of stressors are also seen in animals exposed to chronically elevated levels of the hormone ghrelin. Ghrelin, a stomach derived hormone, is commonly associated with the stimulation of appetite and food intake (particularly the intake of high calorie foods), as well as the accumulation of body fat. Ghrelin appears to be released following exposure to stressors, and thus it is possible that the behavioral and metabolic alterations that are seen following chronic stress paradigms are mediated in part by ghrelin. This research seeks to provide evidence that this is the case, and to determine the parts of the brain directly affected by ghrelin to mediate these effects.

Shawn Hayley, from the Dept. of Neuroscience, was successful in acquiring funding to support his research assessing the mechanisms underlying Parkinson’s Disease. The vast majority of cases of Parkinson’s disease (PD) are of unknown origin, and environmental influences have been repeatedly implicated. That said, certain genetic changes, such as those involving a gene that appears to influence the inflammatory immune system (called LRRK2), might engender a vulnerability to the impact of environmental toxicants. In this research, it is suggested that activation of LRRK2, along with immune system messenger proteins, called cytokines, together give rise to PD. We will test this hypothesis using genetically modified mice (that either lack LRRK2 or express abnormal levels of this gene) and administering certain cytokines, immune agents (e.g. compounds that mimic viral and bacterial infections) and environmental toxicants (e.g. pesticides linked to PD).

, from the Dept. of Health Sciences, together with his research collaborator, Dr. Warren Foster of the Department of Obstetrics & Gynecology at McMaster University were awarded an operating grant to study a novel clinical marker of endometriosis. Endometriosis is an estrogen dependent disease of unknown etiology that affects between 10-15% of reproductive age women which can result in significant pain and interference with everyday activities including work and social interactions. Clinically useful markers of endometriosis are lacking and many women are symptomatic for 8-12 years before achieving a definitive diagnosis. Hence, novel clinical markers of endometriosis are urgently needed. The proposed study will investigate whether brain derived neurotrophic factor (BDNF) is a clinically useful marker of endometriosis that has the potential to offer women with pelvic pain more appropriate, effective, and less costly medical therapies compared to surgery.

For updates on the CHAIM Centre, follow us on !

There’s something a little extra delicious about a barbequed meal and a cold beer on the deck after returning home from a fire-fighting tour. Our crew just finished a 19-day tour in Lac la Biche district in Alberta. We were working on a fire near Cold Lake that grew to 10 000 ha in less than 4 days in the absence of wind—it was dry, and the fuels were ready to burn. Fire behavior predictions foreshadowed lots of work, long days, and short sleeps.

The Alberta government set up a base camp (trailers for a kitchen, diner, bathroom, logistics, radio ops, etc.), and we set up our tents. Everyday on tour is unpredictable—what you’ll see, what you’ll accomplish, when you’ll be going home. A small change in observed weather throughout the day can either increase or suppress fire behaviour, movement, and growth. Despite the abundant unknowns, I’m a creature of habit, and try to create as much of a daily routine as possible for the things I can control.

4:54 am: Alarm goes off.
5:15 am: Morning jog down the basecamp road
5:57 am: Wait in line for breakfast
5:59 am: Grab a bagged lunch

The bagged lunch. Of all the elements and difficulties you face on a daily basis while on tour, the bagged lunch can really be a morale booster or breaker. Looking in your bagged lunch before you get to the line can be destructive, because you KNOW there is going to be a white bread ham sandwich in there, and that’s a day-killer that you just don’t need at 6:00am (or if you’re “lucky”, it’ll be a white bread peanut butter and butter sandwich). It’s not wet feet, bug bites, sleep deprivation, or diminished cigarettes that warrant daily complaints; it’s the white bread ham sandwiches.

On average, the bagged lunch consists of: 3 white bread ham, cheese, and butter sandwiches; one apple; one orange; one dessert square; two juice boxes; and, if you choose to grab one, a bag of chips. It might be immature. It might be selfish. But when you have a daily 30-minute walk through knee-deep muskeg to get to a 20-minute hike through dusty, sooty, burn, and your face is covered in black ash, your B.O. is unrecognizable, and your shin chafe starts to bleed, the last thing you want to pull out of your bagged lunch is a white bread ham sandwich.

By day 8, you’re pretty vocal about how much you hate sandwiches. By day 10, you’re pretty sure you cannot eat another sandwich. By day 14 you’ve boycotted sandwiches, and have started hoarding granola bars to get you through the day. Day 14. That’s two weeks.

Let’s think about this for a minute. Ham, cheese, and butter sandwiches seem to be a fireline base-camp go to—why? Because they’re cheap and easy to make. When there are over 300 people to feed by a staff of 10, you can’t expect anything much fancier. Now think about northern semi-remote districts in Ontario, like Armstrong, or Pickle Lake, and the price of supporting over 200 rangers, where food prices are already outrageous for locals. Should the Ministry be responsible for supporting gourmet meals for the duration of rangers’ stay?

Food is expensive. Food preparation is timely. Exciting meal planning and development requires knowledge. Despite education, it’s surprising how quickly we become bored of eating the same, affordable meals all the time, and how quickly we become drawn to grabbing that bag of chips, or trying to score an extra dessert square. Food quickly becomes a comforting item on fire, as it is for so many people outside of fire.

We know that obesity rates are high among First Nations people. We know that food prices in remote communities are ridiculous. And so we know that the price and practicality to eat healthy is affecting obesity rates. But an underrepresented factor is the availability of variety. While we know that, yes, variety is limited and affects some remote and semi-remote areas, each day that I had a white bread ham sandwich, I was reminded how quickly you become bored of plain food, and how important it is to seek variety in order to continue making healthy choices.

I am aware of the importance of fueling my body with healthy, hearty fuels, and so sometimes I have to remind myself to eat for the nutrients, not the comfort or enjoyment—but what happens when people aren’t as aware of the importance in making healthy decisions regularly? What about those who aren’t aware that they are making unhealthy decisions? What about those who don’t know what a healthy decision is? Considering all these questions, why on earth would someone continue to eat the white bread ham sandwich when they can grab an extra bag of BBQ chips, a Pepsi, and a dark chocolate Mounds bar every day instead?

It’s important to realize that it’s not a divide; it’s not that First Nations people are always choosing unhealthy food options, and white people are saints when it comes to eating—trust me, I know that’s not true. But there’s a point to be made as we KNOW that food options are limited in northern remote and semi-remote communities, and that prices are high. If we want to truly make healthy options more available, it’s not enough to subsidize prices; it’s not enough to add more lettuce and peppers to the shelves. We need to revisit the importance of variety. Options. Explanations. Mentality. Being part of an individual’s built environment, improving overall diet is a complex task; not one that will ever have a simple answer or solution.

6:00am: Switch out 95% of my bagged lunch items with food I scavenged and stowed from dinner the night before.
6:03am: Get changed and gear up for the day
6:25am: Head to the bus, bagged lunch in hand, and get ready for another day’s work on LWF-122.

Author Ariel Root is currently in Kenora in her fourth season working as a forest fire fighter for the Ontario Ministry of Natural Resources and Forestry.  She has a BSc in Food Science & Nutrition from ĐÓ°ÉÔ­´´ University in 2012, and is currently a graduate student in the Health Science, Technology and Policy program at ĐÓ°ÉÔ­´´ University. She has been featured on APTN’s new hit TV show, Playing with Fire, Season 2.

Come back for next week’s instalment.

Photos by Ariel Root

Follow us on !

By Martin Wellman, Department of Neuroscience, ĐÓ°ÉÔ­´´ University

In Statistics Canada’s most recent report on overweight and obesity in 2013, 18.8% of Canadians aged 18 or older were obese based on their body-mass index, while 41.9% of men and 27.7% of women were overweight [1]. We are all aware of these health conditions in Canada and much of the rest of the Western world. Beyond the health factors associated with obesity and overweight, strain is put on the social support system, medical costs rise, and quality of life goes down.

In order to effectively reduce overweight and obesity rates, the issue has to be approached along several fronts
• at the governmental level, through regulation of foods including possibly going so far as banning certain food products or ingredients;
• at the educational level, to increase awareness and promote healthy lifestyles starting at a young age
• at the corporate level, to reduce the use of unhealthy ingredients in products; and
• at the scientific level, to guide governmental policy and educational curricula, as well as to provide an understanding of the physiological systems involved and possibly develop therapeutic agents to aid in weight loss or prevention of weight gain.

In the field of therapeutic drugs, we have seen very little success, often due to unmanageable side effects. A recent example is that of Rimonanbant (trade name Acomplia), initially approved for use in Europe. In 2008, two years after initial approval, the European Medicines Agency recommended the suspension of marketing for Rimonabant, citing that “the benefits of Acomplia no longer outweigh its risks”, including “an approximate doubling of the risk of psychiatric disorders in obese or overweight patients taking Acomplia compared to those taking placebo”. The agency’s Committee for Medicinal Products for Human Use also stated that “these psychiatric side effects could not be adequately addressed by further risk minimization measures” [2]. The drug was withdrawn the following year [3].

In addition to side effects, the weight-loss associated with Rimonabant (in combination with dieting and exercise), while statistically significant, was certainly not enough to bring an obese individual down to what is considered “normal” weight. Data indicated an approximate 5% reduction in weight following one year of treatment in 50% of participants receiving 20 mg/day [4]. This 5% represents an average drop in weight from 105 kg (231 lbs) to 100 kg (220 lbs). When treatment was extended to two years, the reduced weight compared to placebo controls was maintained, but the extent of the weight loss did not increase. This maintenance, however, was an important result of treatment, as many dieters regain the weight they lose.

As is the case with most conditions, the path to effective pharmaceuticals has been, and likely will be, a long road with minor incremental improvements, and possible setbacks, along the way. The challenge of developing pharmaceuticals with minimal side effects stems in large part from the interactions between various physiological systems. Simply put, there is no bodily function or system that acts in isolation. For the example the use of aspirin as an analgesic may also function in prevention or treatment of certain cardiovascular problems.

Our research focuses on a particular hormone called ghrelin. Discovered in 1999, ghrelin promotes feeding and is secreted into circulation primarily, but not solely, by the stomach. Ghrelin levels rise when our body detects low energy, particularly before a meal, and decrease once energy supplies increase, such as after a meal. Injection of ghrelin enhances appetite and feeding and promotes storage of fats in both animals and humans. Once activated, ghrelin binds to a receptor called the growth-hormone secretagogue receptor, also known as GHSR1a. It is this receptor that modulates most of ghrelin’s activities. While we have the tools to block this receptor, or to block activation of ghrelin, we know that doing so can have wide-reaching effects beyond reductions in feeding or fat storage.

The interaction between the ghrelin system and other biological systems is demonstrated by a fascinating phenomenon called receptor dimerization. Dimerization involves two receptors that come together and physically interact. This physical interaction can change how the receptors work, including increases or decreases in sensitivity, and how long the receptor stays active. In some cases, the dimerized complex has properties entirely different from the two receptors it is composed of. GHSR1a can form dimers with many other receptors. One such dimer involves partnering GHSR1a with the dopamine 1 receptor (D1R), which is heavily involved in reward mechanisms. This includes the rewarding feelings associated with such things as eating or sex. When dimerized with GHSR1a, D1R signaling is amplified four-fold. If we administer weight-loss drugs that inhibit GHSR1a, in theory this should also inhibit signaling through D1R, which would reduce our ability to experience pleasure. When this reduction is severe enough, we call it anhedonia, which is associated with psychiatric conditions such as depression. While in most people this reduction in reward may not be so severe, there may be some who are more prone to such negative consequences.

In addition to dopamine’s rewarding effect, it is also capable of making us less hungry. In this case, it is the dopamine 2 receptor (D2R) that is responsible, but only when it is dimerized with GHSR1a. Given this, inhibition of GHSR1a should reduce dopamine’s ability to decrease appetite, which is the opposite to what we would normally expect to happen when GHSR1a is inhibited. An interaction between GHSR1a and other neurochemical systems has also been found, including serotonin (associated with depression and schizophrenia).

This complexity is a reflection of the tight interconnections between various physiological pathways. This is why drug design that achieves a specific purpose without negative side effects is such a challenge. This process of dimerization extends beyond the ghrelin system, and is part of the intricate knowledge needed for the development of drug treatments. This is not, however, a reason to give up hope in terms of pharmaceuticals. As scientists, our primary goal is to understand how these systems work. The more knowledge we gather, the closer we get to more effective treatments.

Based on
Wellman, M. and A. Abizaid (2015). “Growth Hormone Secretagogue Receptor Dimers: A New Pharmacological Target.” eNeuro 2(2).

1. Statistics Canada. Overweight and obese adults (self-reported), 2013. Statistics Canada Catalogue no. 82-625-X 2013 [cited 2015 May 13]; Available from: .
2. European Medicines Agency. Press Release: The European Medicines Agency recommends suspension of the marketing authorisation of Acomplia. 2008 [cited 2015 May 13]; Available from: .
3. European Medicines Agency. Public statement on Acomplia (Rimonabant): Withdrawal of the marketing authorisation in the European Union. 2009 [cited 2015 May 13]; Available from: .
4. Pi-Sunyer, F., et al., Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: Rio-north america: a randomized controlled trial. JAMA, 2006. 295(7): p. 761-775.

Top image courtesy of Mister GC at 
Ice cream image courtesy of stockimages at