Arya M. Sharma, MD

Earlier this week, Bill Colmers and I gave the inaugural Centennial Lecture for our Faculty of Medicine and Dentistry in anticipation of the upcoming 100 year anniversary of the University of Alberta medical school.

In this talk, we discussed why it is so difficult to keep weight off. I presented the clinical problem, and Colmers, the neuroscientist, presented an overview of how the brain affects eating behaviour and regulates body weight.

I was particularly impressed by how Colmers described the respective roles of the hedonic and homeostatic systems in human evolution.

While the hedonic (pleasure seeking) system evolved to help our hunter-gatherer ancestors seek out and take advantage of any highly palatable energy dense foods they happened to come upon, the homeostatic system evolved to protect from wasting away those extra calories that they did ingest.

Thus, according to Colmers, the hedonic system’s job was to make it hard to resist, in fact, make our ancestors to often go to considerable lengths to searching out those rare palatable energy dense foods and then to eat as much of them as possible, whether they were actually hungry or not. They could of course always store those extra calories as fat tissue for later use - a tremendous survival advantage.

In contrast, the job of the homeostatic system was to ‘defend’ those stored calories - in fact, it is designed to regard any accumulation of fat stores as the ‘new normal’ and from then on make sure that this increased level of fatness was maintained (or regained) ever after.

Indeed, the homeostatic system is ‘designed’ to readjust its set point of body weight - after all it has to do this starting from birth as body weight continues to increase as the baby grows into a toddler that grows into a kid and ultimately into an adult.

Unfortunately, the mechanisms that allow the set point to reset to ‘defend’ a progressively higher body weight - generally works in only one direction - after all that is all that is required by nature, where people do not naturally ’shrink’.

Colmers used the analogy of a ratchet to describe how the homeostatic system is designed to defend ever increasing body weights without having the ability to reset itself to a lower body weight even if the person now wants to lose weight.

Once set to a higher weight (e.g. resulting from ‘overindulgence’ driven by the hedonic system or other factors that may promote weight gain), the homeostatic system uses a wide range of mechanisms affecting hunger, satiety, appetite, metabolic rate, etc. to ‘defend’ this weight from then on.

A very helpful analogy I thought, nicely explaining why evolution has given us the mechanisms to gain weight but not to lose it.

AMS
Edmonton, Alberta

Traditionally, dietary counseling has focused largely on client education and prescriptive approaches to promoting better ‘choices’.

Based on the limited success that such approaches have had on changing long-term dietary habits, a rather provocative article by Bradley Applehaus and colleagues from the Rush University Medical Centre, Chicago, Il, published in a recent issue of the Journal of the American Dietetic Association, argues that it is perhaps now time to discard the notion of ‘choice’ in favor of a strategy based on a deeper understanding of the complex interaction between neurobehavioural processes and environmental determinants of overeating.

As the authors discuss, both counselors and clients frequently attribute obesity largely to poor ‘personal choices’ and studies have shown that dietitians rank ‘lack of willpower’ as far more important to the development of obesity than genetic or other biological factors. This is not only contrary to our current understanding of the complex neurobiology of ingestive behaviour but also only serves to stigmatise and frustrate patients, who in turn blame their own ‘failures’ on lack of motivation or personal ‘failings’.

“The term personal choice implies that human behavior derives from conscious, volitional decisions, and connotes that human beings have free will to decide between alternative courses of action independent of biological and environmental forces. An implication of this definition of personal choice is that individuals can be considered causally, financially, and morally responsible for their behavior”

“In contrast to the notion of personal choice, some argue that human behavior is explained by neurobiological processes and their interaction with environmental stimuli. Supporting this deterministic model of personal choice are studies demonstrating that future actions can be predicted by brain activation patterns up to 10 seconds before individuals become aware of having made a decision, behavior is strongly influenced by processes outside of conscious awareness, and individuals can be led to believe that they have caused actions outside of their control.”

Thus, the authors propose that rather than making adoption of a ‘healthy’ diet a matter of choice, dietetic practitioners may better serve their clients by basing their counseling strategies on the emerging understanding of neurobehavioural drivers of eating behaviours, particularly, on the issues of food reward, inhibitory control, and time discounting.

Whereas the concept of ‘food reward’ involving the brain’s complex mesolimbic reward circuitry (as in addictions) is readily evident, as is the complex neurobiology of the prefrontal cortex that determines motivation, impulsivity and inhibitory self-regulation, time discounting refers to the increased value of immediate (short-term) rewards compared to deferred (long-term) benefits routinely demonstrated in psychological testing and deeply ingrained in human behaviour.

Recognising and fully acknowledging how the brain’s neural circuitry that underlies these behaviours interacts with (and is thus ultimately responsive to) environmental situations and cues can perhaps provide a far more realistic and effective counseling strategy.

In their paper, the authors provide several specific examples of how such an approach may work.

For e.g., the tendency for the brain’s reward circuitry to drive the intake of highly palatable foods can be thwarted by eliminating such foods from the personal foodscape and avoiding temptation and exposure to such foods by sticking to grocery lists or online grocery shopping.

Similarly, inhibitory control can be made easier by avoiding situations that challenge (e.g. buffets) or weaken (e.g. stress) inhibitory control.

The tendency to discount time can be countered by focussing on short-term (immediate) rather than long-term (health) goals.

Many of these strategies may seem familiar to present recommendations, however, the context and manner in which these strategies are presented to and discussed with the client would be vastly different.

Thus, rather than making these behaviours a matter of ‘personal choice’ the counseling goal would be to have clients fully understand how their own genetic predispostiion and neurobiology drives them to these behaviours and how they have to adopt these ‘unnatural’ and ‘difficult’ strategies to overcome their ‘nature’.

As the authors point out:

“the model explains eating behaviors that promote obesity without invoking character flaws (eg, lack of willpower). By emphasizing genetically-influenced neurobiological processes that confer vulnerability to overeating in a toxic food environment, the model enables dietetics practitioners to more effectively address obesity without promoting stigma.”

In terms of the counseling process, the authors suggest that this approach

“…acknowledges that patients are working against potent genetic vulnerabilities and a toxic food environment, and normalizes patients’ (and dietetics practitioners’) frustration with failed attempts at weight control.”

and that

“…patients can better control their weight through strategies focused on the interaction between the brain and the environment. For the majority of dietetics practitioners, this second message constitutes a shift in strategy from urging patients to make the tough choices required for weight control to helping patients minimize the number of tough choices they encounter.”

While it remains to be seen whether or not such a shift in strategy will indeed produce better outcomes, I do appreciate the fact that this paper makes a serious attempt at recognising just how effectively biology drives eating behaviour and that the simplistic concepts of ‘personal choice’ and ‘will power’ are clearly not the most effective strategies to counter the toxic food environment that most of us are exposed to.

To use an analogy that I have used before, recognising that someone has a hypersensitive bronchial system that predisposes them to asthma should lead them to avoiding and eliminating air-borne pollutants in their immediate environment rather than simply trying to breathe less.

AMS
Edmonton, Alberta

Hat tip to Annette for pointing me to this article.

Appelhans BM, Whited MC, Schneider KL, & Pagoto SL (2011). Time to abandon the notion of personal choice in dietary counseling for obesity? Journal of the American Dietetic Association, 111 (8), 1130-6 PMID: 21802557

Regular readers will recall the many posts on the issue of intra-uterine epigenetic programming, that is now believed by many to be one of the key drivers of the childhood obesity epidemic.

As more and more human and experimental evidence for this hypothesis accumulates, it is becoming increasingly evident that the intra-uterine environment may play a central role in determining the future risk of obesity in offspring (even much later in life).

This notion is further supported by an interesting study by Ricardo Orozco-Solís and colleagues from the Université de Nantes, France, published in the latest issue of PLoS One, showing that in rats, maternal nutrition during pregnancy is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus (the brain centre that regulates eating behaviours).

In this study, the researchers analyzed the profile of the hypothalamus transcriptome (the sum of all genes expressed as RNAs) in 180 days-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet through pregnancy and lactation.

From the almost 30,000 examined genes, around 700 were up-regulated and 300 down-regulated by early protein restriction.

Most interestingly, the researchers found that perinatal protein restriction permanently altered the expression of two gene clusters regulating a large number of common cellular processes.

While the first gene cluster includes several gate keeper genes regulating insulin signaling and nutrient sensing, the second cluster represents a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel. This network also links temporal and nutritional cues to metabolism through their tight interaction with the circadian clock (in this context readers may recall the recent posts on the link between sleep and obesity).

As pointed out by the authors, these findings clearly show that (protein-) malnutrition during pregnancy and lactation may play a key role in epigenetically programming hypothalamic circuits regulating energy homeostasis.

As blogged before, the key to preventing childhood obesity may well lie in ensuring maternal nutrition and healthy body weights - once born, as with the proverbial horses, the kids may be out of the barn!

AMS
Hamilton, Ontario

Orozco-Solís R, Matos RJ, Guzmán-Quevedo O, Lopes de Souza S, Bihouée A, Houlgatte R, Manhães de Castro R, & Bolaños-Jiménez F (2010). Nutritional programming in the rat is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus. PloS one, 5 (10) PMID: 20975839

Readers may be well aware that the use of cannabis or “hashish” can induce the “munchies”, an acute craving for highly palatable foods.

Now Garron Dodd and colleagues from the University of Manchester, UK, have identified a new brain peptide called hemopressin that acts through cannabinoid receptors to reduce food intake in rats and mice. Their findings are published in the latest edition of the Journal of Neuroscience.

Hemopressin is a short, nine amino acid peptide found in the rat brain that behaves as an inverse agonist at the cannabinoid receptor CB(1), where it inhibits agonist-induced receptor internalization.

In their studies, Dodd and colleagues found that this peptide dose-dependently decreases night-time food intake in normal male rats and mice, as well as in obese ob/ob male mice, when administered centrally or systemically, without any obvious adverse side effects.

Hemopressin specifically blocks the hyperphagic response to CB(1) receptor agonists, while having no effect on eating behaviour in CB(1) receptor null mutant male mice.

Obviously, the discovery of this peptide not only increases our understanding of the complex neurobiology of ingestive behaviour but may also lead the way to new treatments for obesity.

It should however be noted that we have already had potent inhibitors of the CB(1) receptor for the treatment of obesity (readers will recall rimonabant), which were withdrawn from the market due to increased incidence of depression.

Nevertheless, it may well be that endogenous inhibitors of the endocannabinoid system (like hemopressin) may well be better tolerated previous inhibitors of this system.

Perhaps we have not seen the last of our attempts to decrease appetite by blocking the endocannabinoid system just yet.

AMS
Edmonton, Alberta

p.s. You can now also follow me and post your comments on Facebook

Dodd GT, Mancini G, Lutz B, & Luckman SM (2010). The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (21), 7369-76 PMID: 20505104

An important aspect of enjoying food, in addition to the actual taste and mouth feel, is the complex sensory stimulation of the olfaction system. After the food enters the oral cavity, aroma molecules find their way to the sensitive olfactory nerve endings in the nose by making their way up the back of the throat into the nasal cavity (apparently the nose has a clever way of telling whether this aroma is coming from the food on your plate or from the food in your mouth).

This activation of specific brain areas by a retronasally sensed food odor is not only associated with the perception of the aroma of the food that is consumed but is also hypothesized to directly contribute to its satiating effect (sensory-related satiation).

A paper by Rianne Ruijschop and colleagues from The Netherlands, published in the Journal of Agricultural and Food Chemistry, provides a splendid overview of this fascinating area of research.

In this paper, Ruijschop and colleagues describe a series of experiments that examine a wide range of factors that can affect retronasal olfaction-related satiation.

Not surprisingly, solid and semisolid foods that required a greater amount of chewing and swallowing elicited a stronger and longer-lasting retronasal aroma release pattern than the rather short-lived spiked pattern observed with liquid foods. A higher extent of retronasal aroma release may therefore be one of the explanations why solid foods appear to be more satiating than liquid foods.

Indeed, the researchers did observe a negative trend between the extent of retronasal aroma release and the amount of ad libitum food intake. Subjects who had a higher extent of retronasal aroma release tended to consume less.

However, retronasal aroma release intensity and profile morphology appeared to be subject specific, which may support the hypothesis that subject differences in the extent of retronasal aroma release are linked to subject differences in sensory satiation and food intake behavior.

In further studies, the researchers found that certain aromas were better at eliciting a satiation response than others. Thus, aromas that suggest fat content (i.e., lactones) were less effective in creating a satiation response than aromas suggesting carbohydrate content (i.e., maltol) or the breakdown of protein (i.e., “animalic”). In a separate experiment, custard products with the addition of maltol or animalic at sensory detection threshold were able to increase subjects’ feeling of fullness significantly.

These results are in line with the observation that macronutrients have different satiating efficiencies, in which protein is more satiating, followed by carbohydrate and fat as least satiating.

Based on these studies, the authors suggest that these findings may provide the rational for developing strategies for prolonging the duration of retronasal aroma release during food consumption.

Examples could include food products with an increase of aftertaste or an increased or lingering aroma release via flavor delivery systems or encapsulation technology or the development of long-chewable food structures in beverages that evoke substantially more oral processing and an increase in transit time in the oral cavity.

Furthermore, a reduction in bite size by tailored packaging may support the “right” oral processing behavior in food products. Interestingly, as blogged previously, eating too fast has been previously associated with increased risk for obesity.

Differences in the extent of retronasal aroma release during consumption may be one of the reasons that people vary in their satiation characteristics, which may prevent them from overeating or not. Whether or not there is a difference in this effect between normal weight and obese people is not known.

As the authors point out, integration of these findings into novel food products may provide a new way to reduce food consumption.

While we wait for these new foods here are my retronasal olfaction-based satiation tips:

1) Take small bites
2) Chew your food thoroughly
3) Don’t drink your calories

Remember, the main problem with fast food is not the “food” - it’s the “fast”.

Happy Holidays,

AMS

p.s. As I am planning to take it easy for the next couple of days you are likely to see sporadic posts till the new year.