To conclude this brief series on our new exhaustive review of the putative health benefits of long-term weight-loss maintenance, published in Annual Reviews of Nutrition, here is the summary paragraph of our findings:
“Obesity is well recognized as a risk factor for a wide range of health issues affecting virtually every organ system. There is now considerable evidence that intentional weight loss is associated with clinically relevant benefits for the majority of these health issues. However, the degree of weight loss that must be achieved and sustained to reap these benefits varies widely between comorbidities. Downsides of weight loss that is too rapid and/or extreme may occur, as in the increased risk of gallbladder disease, the presence of excess residual skin, or deterioration in liver histology. Uncertainty also remains about the potential benefit or harm of intentional weight loss on patients presenting with some chronic diseases and on overall mortality. Clearly, well- controlled prospective studies are needed to better understand the natural history of obesity and the impact of weight-management interventions on morbidity, quality of life, and mortality in people living with obesity.”
The is much left to be done and answering some of these questions will become progressively easier as better treatments for obesity become available.
In our exhaustive review of the potential health benefits of intentional long-term weight loss, published in Annual Reviews in Nutrition, I discussed in yesterday’s post, we also noted a number of issues that remain unresolved.
- The precise definition of success in terms of weight loss remains controversial, and the dogmatic assumption that prolonged periods of sustained weight loss (greater than 10 years) are more likely than shorter periods to have a beneficial effect on health out- comes has never been challenged.
- Some evidence suggests that intentional weight loss may lead to meaningful reductions in several conditions, such as COPD, and cancer risk with a short latency time, although data from randomized trials are not yet available to support this hypothesis.
- Future studies on the relationship between long-term weight loss and suicide are needed, especially in diverse populations, subgroups of patients, and those who engage in other long-term weight-loss strategies apart from the use of antiobesity medications and bariatric surgery. The potential relationship between failed weight-loss attempts and suicide ideation needs to be evaluated.
- There is ongoing controversy over the findings from epidemiological studies on the relationship between weight loss and mortality. Data from controlled studies in this regard are very limited.
Clearly, as we discussed at length here at the ongoing Canadian Obesity Network’s Obesity Research Summer School (Boot camp), much remains to be done for young researchers planning a career in this field.
While the health benefits associated with intentional weight loss for some complications of obesity (such as elevated lipids and diabetes) are well documented, high-quality studies to back many other potential health benefits are harder to find.
Just how well (or poorly) the putative health benefits of long-term intentional weight loss are documented for each of the many conditions associated with obesity, is now detailed in a comprehensive review of the literature that we just published in the Annual Reviews of Nutrition.
The 40 page long review, which includes almost 250 relevant publications, supports the following main findings:
- Defining and assessing clinically relevant obesity and weight change are challenging tasks. In a given individual, there is often little relationship between the magnitude of obesity and measures of health.
- Despite its modest effect on long-term weight loss, behavioral modifications thatimprove eating behaviors and increase physical activity constitute a cornerstone for integral and sustainable weight management.
- Intentional weight loss is associated with a clinically relevant reduction in blood pressure, improvement in cardiac function, and reduction in cardiovascular events. The duration and magnitude of weight change required to achieve a significant benefit are still unclear.
- In individuals with impaired glucose metabolism at any stage, intentional weight loss achieved by any means is associated with a proportional reduction in T2DM prevalence, severity, and progression.
- Intentional weight loss is consistently associated with a clinically relevant reduction in triglycerides and increase in HDL cholesterol. The effects of weight loss on LDL cholesterol are less consistent.
- Overall, nonalcoholic fatty liver disease is commonly associated with excess weight and can show marked improvement with behavioral, pharmacological, and/or surgical weight loss. Very rapid weight loss, however, may worsen liver histology in some patients. Simi- larly, gallbladder disease is not only common in patients presenting with obesity but also highly prevalent after intentional weight loss.
- Obesity is widely recognized as a key modifiable risk factor for osteoarthritis, with sig- nificant improvements in pain and function reported with weight loss.
- Obstructive sleep apnea and obesity hypoventilation syndrome tend to improve with moderate weight loss; however, complete resolution is not common and is related to very significant weight loss.
- Asthma and COPD are clearly associated with obesity. Sustained weight loss seems to be associated with a significant improvement in asthma symptoms. Data for COPD are rather limited.
- Pregnant women who under go bariatric surgery seem to be less likely to present obstetric complications such as gestational diabetes, preeclampsia, and macrosomia.
- Data on weight loss and suicide are controversial. Caution may be in order when con- sidering bariatric surgery in patients with a history of suicide ideation or attempt.
- Data suggest that long-term weight loss is associated with an improvement in health- related quality of life. The amount of weight loss required to achieve a significant change, however, remains controversial.
However, there are many other issues where putative benefits of intentional weight loss remain even less clear than with the above.
For many conditions we will likely not know the long-term benefits of obesity treatments till better treatments become available and are tested in affected individuals.
While I’m here at the 10th Canadian Obesity Network Summer School (Boot Camp), in the Canadian Rockies, it is perhaps of interest to note that one of the founding faculty of this school, Denis Richard from Laval University, has just published a paper in Nature Reviews Endocrinology, which nicely reviews the complex neurobiology of energy balance.
The paper focuses largely on the “energy out” part of energy homeostasis, which is partly determined by the themogenesis of brown adipose tissue and mediated by the sympathetic nervous system.
Thus, several areas of the brain work together in complex neuronal networks involving a host of neuronal systems including the opioid, endocannabinoid and melanocortin systems, that not only control appetite and eating behaviour but also thermogenesis.
These neuronal systems, in turn receive inputs from a wide range of peripheral organs including the gut, liver and adipose tissue via hormonal and neuronal pathways that signal energy stores and nutritional status.
The paper also discusses how some of these findings may be relevant to the development of novel treatments for obesity.
For researchers and students: the paper includes a number of excellent graphics that nicely illustrate these systems.
This year’s 10th annual Canadian Obesity Summer School (also known as “Boot Camp”) is now in session.
This year’s class includes Canadian trainees from the Universities of British Columbia, Alberta, Calgary, Manitoba, Ottawa as well as McMaster, McGill, Queen’s and Memorial Universities.
International trainees represent nine countries including Belgium, Brazil, Lebanon, Germany, Israel, Japan, Saudi Arabia, Spain, and the United Arab Emirates.
Attendees work in obesity research fields as diverse as public health, genetics, basic science, nutrition, exercise physiology, psychology, rehabilitation, clinical medicine and bariatric surgery.
I look forward to a week full of exciting interactions with all of the trainees and faculty, in what I am sure will be another memorable Summer School.
Hard to believe, but this weekend I am off to my 10th annual Canadian Obesity Network Summer Boot Camp – once again in Kananaskis in the Canadian Rockies.
As every year, I look forward to spending 9 days with an enthusiastic bunch of young obesity researchers and professionals as well as my faculty colleagues, who will teach about everything from genetics and molecular biology to public health and clinical management.
More importantly, the intense networking involved in this event, as in the past, should lead to a lasting network of professional friendship across disciplines, research interests and countries.
I am certain that the almost 300 alumni of this camp can attest to how much this experience has influenced their thinking and professional development.
Thanks to all at the Canadian Obesity Network, who make this annual event possible.
A paper by Such and German, published in Veterinary Record, shows that a significant proportion of show dogs in the UK would be considered to have overweight or obesity.
The researchers did internet searches to identify 40 pictures per breed of 14 obese-prone dog breeds and 14 matched non-obese-probe breeds that had appeared at a major national UK show (Crufts). Of 1120 photographs initially identified, 960 were suitable for assessing body condition using a previously validated method, with all unsuitable images being from longhaired breeds.
None of the dogs (0%) were underweight, 708 (74%) were in ideal condition and 252 (26%) were overweight with pugs, basset hounds and Labrador retrievers were most likely to be in the latter category.
In contrast, standard poodles, Rhodesian ridgebacks, Hungarian vizslas and Dobermanns were least likely to be overweight.
In the discussion, the authors wonder whether or not breed standards should be redefined to be consistent with a dog in optimal body condition (read – body weight).
As someone, who could not really care less about breed standards and pedigrees (having shown dogs at dog shows myself as a kid), I find this paper of interest, as it reflects our thinking about appearances, that is by no means limited to animals.
The mental health and physical benefits of owning a dog are well-documented – whether they meet show standards or not, is probably not what determines their usefulness as (wo)man’s best friend.
The amygdala is a part of the so-called limbic system that performs a primary role in the processing of memory, decision-making, and emotional reactions. The amygdala has also been implicated in a variety of mental health problems including anxiety, binge drinking and post-traumatic stress syndrome.
A study by Xu and colleagues, published in the Journal of Clinical Investigation now shows that in mice, activity of the estrogen receptor–α (ERα) in the medial amygdala may have a profound influence on the development of obesity – an effect, which appears to me largely mediated through effects on physical activity.
Building on previous work showing that ERα activity in the brain prevents obesity in both males and female rats, the researchers used a series of complex experiments to demonstrate that specific deletion of the ERα gene from SIM1 neurons, which are highly expressed in the medial amygdala, cause a marked decrease in physical activity and weight gain in both male and female mice fed with regular chow, without any increase in food intake. In addition, this deletion caused increased susceptibility to diet-induced obesity in males but not in females.
Deletion of the ERα receptor also blunted the body weight-lowering effects of a glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate.
In contrast, over-expression or stimulation of SIM1 neurons increased physical activity in mice and protected them from diet-induced obesity.
These findings point to a novel mechanism of neuronal control of physical activity, which in turn appears to have important effects on the susceptibility to weight gain.