Transcriptional Control of Energy Regulation

To students of human physiology, the commonly held view that obesity is simply a matter of energy in and energy out is nothing short of laughable. Indeed, there are perhaps no other biological functions of more importance for survival of an organism, than those that regulate energy uptake, storage and expenditure – functions, without any form of life would be impossible. Thus, the finely tuned complex and often highly redundant pathways that have evolved to optimize energy metabolism have evolved to readily switch from states of feeding to starvation with shifts in substrate use (both qualitative and quantitative) – functions that are controlled by hundreds (if not thousands) of genes. Getting these genes to work in concert, requires a complex system of gene regulation, by which individual genes are switched on an off (to allow or stop protein synthesis) in various tissues to just the right amount at just the right time – a process known as transcriptional control. Now, a comprehensive review by Adelheid Lempradl and colleagues, published in Nature Genetics, summarizes the multitude of interlinked processes that control transcription of genes involved in energy homeostasis. As the authors explain, “Transcriptional control is the sum of the cellular events that select and dose gene transcription. In simple terms, these events converge on the regulation of gene locus accessibility and polymerase activity (including recruitment, pausing, processivity and termination).” “Energy homeostasis requires multi-layered regulation via dynamic, often periodic, expression of metabolic pathways to properly anticipate and respond to shifts in energy state.” “Transcription factors act by binding to specific regulatory DNA sequences, thus controlling the transcriptional output of defined target gene sets. They cooperate with co-regulators, which either promote (co-activators) or inhibit (co-repressors) transcription. Together, they build feedback networks and control the stability and responsiveness of energy homeostasis. Metabolic cells use receptors and metabolic machinery to generate specific signalling responses to endocrine inputs (for example, insulin, glucagon or leptin receptors) or metabolic inputs (for example, the primary energy metabolism machinery itself).” The papers goes on to discuss at length the various regulator, co-regulators and the plethora of epigenetic modifiers that determine how these factors do their job of activating or deactivating relevant genes throughout the body. Why is any of this important? “Rapid progress is currently being made in research on chromatin-based regulation of gene expression. Particular unknowns include the mechanisms that establish long-term set points or priming of gene expression. Identifying the processes that… Read More »

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Always Hungry? Blame It On Food Porn

There is no doubt that living in a society in which we are constantly surrounded by highly palatable foods makes not overeating a challenge for most of us. Now, an interesting paper by Charles Spence and colleagues from Oxford University, published in Brain and Cognition, makes a strong case for how exposure to images of desirable foods (which they label ‘food porn’, or ‘gastroporn’) via digital interfaces might be inadvertently exacerbating our desire for food (what they call ‘visual hunger’). In their paper, the authors review the growing body of cognitive neuroscience research demonstrating the profound effect that viewing such images can have on neural activity, physiological and psychological responses, and visual attention, especially in the ‘hungry’ brain. Beginning with a brief discussion of evolutionary aspects of vision and food, the authors remind us that, “Foraging – the search for nutritious foods – is one of the brain’s most important functions. In humans, this activity relies primarily on vision, especially when it comes to finding those foods that we are already familiar with. In fact, it has been suggested that trichromatic colour vision may originally have developed in primates as an adaptation that facilitated the selection of more energy-rich (and likely red) fruits from in-amongst the dark green forest canopy.” “The brain is the body’s most energy-consuming organ, accounting for somewhere in the region of 25% of blood flow, or rather, 25% of the available consumed energy. Note that this figure is even higher in the newborn human, where the brain absorbs up to two thirds of the energy that is consumed by the developing organism. As Brown notes: “In embryos, the first part of the neocortex to develop is the part which will represent the mouth and tongue…” As the brain grew in size over the course of human evolution, the demands on the visual system to efficiently locate nutrients in the environment would likely also have increased.” This notion is not trivial given our current environmental exposure to a multitude of food images: “Our brains learnt to enjoy seeing food, since it would likely precede consumption. The automatic reward associated with the sight of food likely meant another day of sufficient nutrients for survival, and at the same time, the physiological responses would prepare our bodies to receive that food. Our suggestion here is that the regular exposure to virtual foods nowadays, and the array of neural, physiological,… Read More »

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CON Co-Hosts the International Congress on Obesity in Vancouver

As Canada’s national representative in the World Obesity Federation (formerly IASO), the Canadian Obesity Network is proud to co-host the 13th International Congress on Obesity in Vancouver, 1-4 May 2016. The comprehensive scientific program will span 6 topic areas: Track 1: From genes to cells For example: genetics, metagenomics, epigenetics, regulation of mRNA and non–coding RNA, inflammation, lipids, mitochondria and cellular organelles, stem cells, signal transduction, white, brite and brown adipocytes Track 2: From cells to integrative biology For example: neurobiology, appetite and feeding, energy balance, thermogenesis, inflammation and immunity, adipokines, hormones, circadian rhythms, crosstalk, nutrient sensing, signal transduction, tissue plasticity, fetal programming, metabolism, gut microbiome Track 3: Determinants, assessments and consequences For example: assessment and measurement issues, nutrition, physical activity, modifiable risk behaviours, sleep, DoHAD, gut microbiome, Healthy obese, gender differences, biomarkers, body composition, fat distribution, diabetes, cancer, NAFLD, OSA, cardiovascular disease, osteoarthritis, mental health, stigma Track 4: Clinical management For example: diet, exercise, behaviour therapies, psychology, sleep, VLEDs, pharmacotherapy, multidisciplinary therapy, bariatric surgery, new devices, e-technology, biomarkers, cost effectiveness, health services delivery, equity, personalised medicine Track 5: Populations and population health For example: equity, pre natal and early nutrition, epidemiology, inequalities, marketing, workplace, school, role of industry, social determinants, population assessments, regional and ethnic differences, built environment, food environment, economics Track 6: Actions, interventions and policies For example: health promotion, primary prevention, interventions in different settings, health systems and services, e-technology, marketing, economics (pricing, taxation, distribution, subsidy), environmental issues, government actions, stakeholder and industry issues, ethical issues Early-bird registration is now open – click here Abstract submission deadline is November 30, 2015 – click here For more information including sponsorship and exhibiting at ICO 2016 – click here I look forward to welcoming you to Vancouver next year. @DrSharma Toronto, ON  

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Are We More Susceptible to Obesity Than Before?

Regular readers will be familiar with my wariness of epidemiological data on diet and activity – especially, when these are self-reported. Nevertheless, for what it is worth, a publication by Ruth Brown and colleagues from York University, Toronto, published in Obesity Research and Clinical Practice, suggests that people today may be more susceptible to obesity than just a few decades ago. The study looks at self-reported dietary from 36,377 U.S. adults from the National Health and Nutrition Survey (NHANES) between 1971 and 2008 and physical activity frequency data from 14,419 adults between 1988 and 2006 (no activity data was available from earlier years). Between 1971 and 2008, BMI, total caloric intake and carbohydrate intake increased 10-14%, and fat and protein intake decreased 5-9%. Between 1988 and 2006, frequency of leisure time physical activity increased 47-120%. However, for a given amount of caloric intake, macronutrient intake or leisure time physical activity, the predicted BMI was up to 2.3kg/m2 higher in 2006 that in 1988. So unless there was some major systematic shift in what people were reporting (which seems somewhat unlikely) it is clear that factors other than diet and physical activity may be contributing to the increase in BMI over time – or in other words, it appears that people today, for the same caloric intake and physical activity, are more likely to have a higher BMI than people living a few decades ago. There are of course several plausible biological explanations for these findings including epigenetics, obesogenic environmental toxins, alterations in gut microbiota to name a few. If nothing else, these data support the notion that there is more to the obesity epidemic than just eating too much and not moving enough. @DrSharma Edmonton, AB

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The Cost-Saving Argument For Obesity Prevention Is No Better

Yesterday, I suggested that using a cost-saving argument to justify treatments for obesity reeks of discrimination. I argued that even if obesity treatment costs the system money, it needs to be delivered in the same way that we deliver treatments for other conditions – not because they save money, but because that’s what people living with those conditions deserve. But the “cost-saving” argument is not just used to justify treatment for obesity – it is also regularly and widely used to justify spending money on obesity prevention. The usual line of argumentation is that x dollars spent on obesity prevention will save y times x dollars in healthcare spending, which is why we need to prevent obesity. This is nonsense. We should be preventing obesity whether or not it saves money for the healthcare system, simply because obesity (defined here as excess weight that actually causes health problems) negatively impacts health and well-being. If this costs money, so be it. Obviously, no one is asking anyone to simply pay for everything (prevention or treatment) just because it is the right thing to do, no matter the cost. In real life cost does matter and there is a fiscal responsibility to spend money on things that are effective and deliver real benefits – but let us not wander into weighing one disease against another in making that decision. And most certainly the question of “fault and responsibility” leads to a very slippery slope, given that so much of what affects our health (from infections to cancer, from accidents to chronic diseases) is often avoidable. The question really boils down to whether or not there are effective ways to prevent obesity – if there are, they need to be funded, whether they save money or not. @DrSharma Edmonton, AB  

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