Does NPY Play a Role in Maintaining The Weight Setpoint?
As regular readers of these posts are well aware, the Holy Grail of obesity is how to lower the body weight setpoint , which tends to reset to progressively higher weights with weight gain and then acts to “defend” against weight loss, virtually guaranteeing weight regain in the vast majority of people who try to lose weight. Now, a study by Yonwook Kim and Sheng Bi published in the American Journal of Physiology, shows that knocking down neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) can reverse the weight gain induced by a high-fat diet in rats. Following the induction of significant weight gain by feeding rats a high-fat diet (HFD), which not only increased body weight but also induces insulin resistance, the obese rats received bilateral DMH injections of an adenovirus vector that specifically knocked down NPY in this region of the brain. Not only did the NPY knockdown rats exhibit normal food intake and a reduced body weight, their glucose tolerance and insulin sensitivity also reverted to that seen in lean control rats, an effect that was maintained even over weeks of follow up. While these studies do not exactly prove the importance of NPY in the establishment or maintenance of the body weight “set point”, they do suggest that blocking NPY in the DMH (e.g. through an NPY inhibitor) may provide a potential target for the treatment of obesity and diabetes. @DrSharma Edmonton, AB
Inequalities in Access To Bariatric Surgery in Canada
Despite a substantial recent increase in bariatric surgery in Canada, there are still substantial differences in access to this treatment across the country. As I discuss in an editorial published this week in CMAJ, annual access to bariatric surgery (2012-13) per 1,000 individuals living with a BMI >= 35 kg/m2 (2007-2010 prevalence) in Canada is around 5.4, however, this number ranges from as high as 9.6 in Quebec to as low as 1.1 in Nova Scotia – an almost 10-fold difference (bariatric surgery is not available in Prince Edward Island or the Territories). To catch up with the current rate of surgery in Quebec, Alberta would need to perform an additional 813 procedures a year, while BC would need an additional 805 and Nova Scotia an additional 463 per year. Overall, bringing the rate of surgery across Canada to the current rate in Quebec, would require an additional 5,129 surgeries per year. However,, even bringing the rate of bariatric surgery across Canada to the current rate in Quebec may not be enough to significantly reduce the burden of severe obesity across Canada. This, must not be an argument against further increasing access to surgery – there is no doubt that the vast majority of the 1000s, who currently do manage to get surgery benefit significantly from this intervention. While it is important to acknowledge that obesity competes for scarce resources in strapped health care systems and that choices must be made about what services/treatments to provide, we must remember that bariatric surgery is currently the only effective long-term treatment for people living with severe obesity. Despite all the risks inherent in any surgical procedure, and the fact that the occasional patient may struggle to lose weight or end up putting it back on, surgery currently remains the best treatment we have. Nevertheless, as I point out in the editorial, “Even as provinces work to increase access to bariatric surgery, other aspects of bariatric care cannot be ignored. For one, efforts at secondary prevention, to reduce and limit weight gain in individuals already carrying excess weight must be increased. Given the over 6 million Canadian adults and children living with obesity, these services must be provided at the primary care level rather than at specialized centres. Secondly, these services need to apply the established tenets of chronic disease management to obesity, which include patient education, self-management and ongoing follow-up and support. These principles are… Read More »
Leaders Have To Understand, Accommodate, Embrace & Support Diversity
Earlier this week, I spoke at a leadership lecture series on barriers to participation at the Peter Lougheed Leadership College at the University of Alberta. The speaker series was hosted by the principal of the college,the Right Honourable Kim Campbell, who served as Canada’s 19th prime minister in 1993. While I spoke about the particular challenges and barriers faced by Canadians living with obesity and how these can be accommodated and supported in the workplace and society in general, other speakers spoke on the accommodation of individuals living with other challenges. Thus, Kelly Falardeau, herself a victim and advocate for burn survivors and Deryk Beal, one of Canada’s leading clinician scientists on stuttering and other speech impediments, joined me in speaking on the importance of diversity and the need to identify obstacles to social inclusion that keep individuals from reaching their full potential. In my presentation I did my best to portray the biological, physical, emotional and societal challenges that Canadians living with obesity face everyday. Here is what I asked the students to think about: “So how can we help people living with such barriers? For one, let us educate ourselves on the real issues – if there was an easy solution that actually worked, believe me my clinic would be empty. Secondly, let us show some respect for people who wake up with this barrier every single morning and go through their day – for the most part doing everything everyone else does. Thirdly, let us acknowledge that once you have obesity there is no easy way back. I have patients who have lost their entire weight over on diet after diet after diet only to put the weight back again. Diet and exercise is simply not enough for most people – surgery works but is not available and not scalable – we cannot do surgery on 120,000 Albertans. So let us not pretend that there is an easy solution to the problem – we simply don’t have enough treatments that work. Fourthly, till we do come up with more treatments that actually work or maybe even get our act together on prevention, let us not make life harder for people living with this barrier than it has to be. We can do many things to accommodate people living with obesity – we accommodate people with all kinds of “special needs” at home, in society in the workplace –… Read More »
Promising Data For Setmelanotide For Genetic Obesity
One of the most common genetics variations related to obesity found in the general population involves the melanocortin-4 (MC4) receptor, which plays a key role in appetite regulation. Now Rhythm Pharmaceuticals released its first data on the use of their novel MC4-R agonist setmelanotide in patients with obesity and proven MC4-R defects. According to their press release, “In this pilot study, obese (BMI >/= 30kg/m2) patients with a heterozygous MC4R loss-of-function mutation were enrolled in a double-blind, placebo-controlled, randomized, parallel-group study for 4 weeks. Eight patients (six active, two placebo) received placebo or RM-493 at 0.01 mg/kg/day (~ 1 mg/day) by continuous subcutaneous infusion. Key endpoints were safety, weight loss, waist circumference, and caloric intake. Setmelanotide was well tolerated over 4 weeks, with no serious adverse events or discontinuations. The most common side effects were headache and skin tanning, with the latter believed to be due to off-target activity at the related melanocortin-1 receptor. Setmelanotide demonstrated strong trends for placebo-subtracted weight loss (2.62 kg; p=0.088); WC (5.1 cm; p=0.188) and daily caloric intake (351 kCal/day; p=not significant), without clinically important effects on heart rate or blood pressure.” Overall, the company has taken (the perhaps wise) option of focussing their development program on genetic forms of obesity. Currently they have an ongoing Phase 2 setmelanotide trial for the treatment of Prader-Willi syndrome and a second Phase 2 trial for the treatment of pro-opiomelanocortin (POMC) deficiency obesity, a very rare, life-threatening genetic disorder of the MC4 pathway associated with unrelenting appetite and obesity. Clearly, this will be a space to watch. @DrSharma Edmonton, AB
Most People Have No Clue As To How Many Calories They Expend Exercising
Eyeballing and “guesstimating” are the worst possible ways to determine whether or not you are eating the right amount of calories after a bout of exercise. This, according to a study by Ruth Brown and colleagues from Toronto’s York University, published in Medicine and Science in Sports and Exercise. The study included 58 adult men and women of either normal weight (NW) or overweight (OW), who reported either attempting (WL) or not attempting weight loss (noWL) Following 25 mins of exercise on a treadmill at either a moderate (60% HRmax) or a vigorous intensity (75% HRmax), participants were asked to estimated the number of calories they expended through exercise and create a meal that they believed to be calorically equivalent to the amount of calories they had just burnt. Both the moderate and intense exercise groups were on average spectacularly wrong in their estimates. In contrast, the active weight loss (WL) groups appeared to do far better at estimating energy consumption than the non-WL groups. As an example, following vigorous exercise, the OW-noWL overestimated energy expenditure by 72%, and overestimated the calories in their food by 37%. Although the WL groups did better, all groups showed a wide range of over and underestimation (-280 kcal to +702 kcal). These findings show that while most people tend to over or underestimate caloric expenditure with exercise, overweight adults who are not attempting weight loss may be even more off the mark than others. The most obvious solution would be to use some kind of monitor that does a better job of predicting calories consumed that just guessing. That is of course, if overcompensating is not your goal (as in people who actually gain weight when they begin exercising). For those interested in staying in energy balance, perhaps simply stepping on the scale regularly during the week should be enough. For those interested in losing weight, they may need to be reminded that exercise (alone) is actually a pretty inefficient way to lose weight, so the calories burnt during exercise probably don’t matter all that much for weight management (despite all other benefits of exercise – its the calories you eat or drink that count). @DrSharma Edmonton, AB
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