The Problem With Brown Fat Stimulation
Brown Fat Cells in White Fat Tissue
Brown adipose tissue is a thermogenic organ, whose sole purpose is to burn calories, which it does with remarkable efficiency (to generate heat).
Not surprisingly, much current research focuses on harnessing this tissue to control or even reduce body weight.
Now a paper by Aaron Cypess and colleagues from the Joslin Diabetes Center in Boston, published in Cell Metabolism, describes the use of the β3-adrenergic receptor (AR) agonist mirabegron, a drug normally used to treat bladder dysfunction, to stimulate brown adipose tissue in humans.
The studies were carried out in 12 healthy young lean male volunteers, who were each given a single 200 mm dose of mirabegron.
Subsequent imaging studies using PET and CT scanning showed substantial activation of brown adipose tissue depots associated with an rise in resting metabolic rate of over 200 cal per day.
Unfortunately, these changes were accompanied by a significant rise in heart rate and blood pressure, not exactly a desired effect when it comes to reducing cardiometabolic risk.
Indeed, these “side-effects” of β3-AR stimulation has been noted before and has resulted in previous attempts to harness this system to be abandoned for human use.
Nevertheless, this study does prove the point that stimulating brown fat in humans can result in a significant increase in metabolic rate.
If this tissue is ever to be harness for weight management, researchers will need to find a way to activate this tissue without also stimulating the sympathetic nervous system (which will still leave them with the problem of heat dissipation – simply burning calories will always result in thermogenesis, which can have quite unpleasant side effects).
@DrSharma
Toronto, ON
Cypess AM, Weiner LS, Roberts-Toler C, Elía EF, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, & Kolodny GM (2015). Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist. Cell metabolism, 21 (1), 33-8 PMID: 25565203
Can’t Wait To Lose Weight? Then You May Not Understand The Problem
Delayed reward discounting is a psychological phenomenon where we tend to see more value in a small immediate reward than in a larger reward promised later (simply put, would you prefer to receive $100 now or rather have $1000 at the end of the year?). In health terms, this may mean something along the lines of, “Would you rather have those extra fries with that, than not have a heart attack 20 years from now?”
Now, a study by Seung-Lark Lim and Amanda Bruce, published in Appetite developed a temporal discounting measure based on weight-loss rewards, that works similar to the more commonly used monetary reward discounting methods.
Both Monetary Choice Questionnaire (MCQ), and an adapted weight version of the MCQ with weight loss as the reward, were administered to healthy young adults, who also completed self-reports that measure obesity-related cognitive variables.
Not surprisingly, the participants who expressed a desire to lose weight, did indeed discount weight-loss rewards over time (which incidentally correlated with their temporal discounting of monetary rewards).
More interestingly, the authors also found that higher temporal discounting for weight loss rewards (i.e., preference for immediate weight loss) as associated with beliefs that obesity is under obese persons’ control and largely due to lack of willpower.
In other words, the more someone believes that body weight is under their control and simply a matter of willpower, the less willing they are to patiently wait for it to happen – even if a slower rate of weight loss may in the end lead to greater weight loss (which it unfortunately does not).
These findings certainly explain the reason why the weight industry does well to promise rapid weight loss – even when chances for long-term success may be remote.
It is clearly in their interest to promote the idea that anyone can be at any weight they chose and losing weight is simply a matter of willpower (or ponying up the dough).
@DrSharma
Copenhagen, DK
Lim SL, & Bruce AS (2015). Can’t wait to lose weight? Characterizing temporal discounting parameters for weight-loss. Appetite, 85, 8-13 PMID: 25450897
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Does The Media Depiction Of Obesity Hinder Efforts To Address It?
A study by Paula Brochu and colleagues, published in Health Psychology, suggests that the often unflattering depiction of people living with obesity in the media (as in the typical images of headless, dishevelled, ill-clothed individuals, usually involved in stereotypical activities – holding a hamburger in one hand and a large pop in the other or pinching their “love handles”), may well play a role in the lack of public support for policies to address this issue.
The researchers asked participants to read an online news story about a policy to deny fertility treatment to obese women that was accompanied by a nonstigmatizing, stigmatizing, or no image of an obese couple. A balanced discussion of the policy was presented, with information both questioning the policy as discriminatory and supporting the policy because of weight-related medical complications.
The findings of the study show that participants who viewed the article accompanied by the nonstigmatizing image were less supportive of the policy to deny obese women fertility treatment and recommended the policy less strongly than participants who viewed the same article accompanied by the stigmatizing image.
Given that negative and stigmatising images of people with obesity are the rule rather than the exception in media reports about obesity, the authors suggest that simply eliminating stigmatizing media portrayals of obesity may help reduce bias and foster more support for policies to address this problem.
Readers may wish to visit the Canadian Obesity Network’s image bank Picture Perfect At Any Size of non-stigmatizing images of people living with obesity that are available for free download for educational and media purposes.
@DrSharma
Copenhagen, DK
Canadian Clinical Practice Guidelines For Obesity: We Need More Than Diet and Exercise
Yesterday, saw the release of new Clinical Practice Guidelines from the Canadian Task Force on Preventive Health Care to help prevent and manage obesity in adult patients in primary care.
Similarly to the Endocrine Society’s Guidelines for the pharmacological treatment of obesity (see yesterday’s post), the authors use a GRADE system to rank and rate their recommendations.
Key recommendations are summarized as follows:
- Body mass index should be calculated at primary health care visits to help prevent and manage obesity.
- For normal weight adults, primary care practitioners should not offer formal structured programs to prevent weight gain.
- For overweight and obese adults health care practitioners should offer structured programs to change behaviour to help with weight loss, especially to those at high risk of diabetes.
- Medications should not routinely be offered to help people lose weight.
Virtually all of these recommendations are supported by evidence that is rated between moderate to very low, which essentially leaves wide room for practitioners to either do nothing or whatever they feel is appropriate for a given patient.
The guidelines do not discuss the role of bariatric surgery (arguably the most effective treatment for severe obesity) and make no recommendations for when this should be discussed with patients.
The rather subdued recommendations for the use of medications is understandable, given that the only prescription medication available for obesity in Canada is orlistat (why the authors chose to also discuss metformin, which is not indicated for obesity treatment, is anyone’s guess).
Overall, the reader could easily come away from these guidelines with a sense that obesity management in primary care is rather hopeless, given that behavioural interventions are modestly effective at best (which is probably why the authors recommend that these not be routinely offered to patients at risk of weight gain).
Indeed, it is hard to see how primary care practitioners can get more enthusiastic about obesity management given this rather limited range of treatment options currently available to Canadians.
If there is anything to take away from these guidelines, it is probably the simple fact that we desperately need more effective treatments for Canadians living with obesity.
@DrSharma
Edmonton, AB
Endocrine Society Clinical Practice Guidelines For The Pharmacological Treatment of Obesity
Last week, the US Endocrine Society released a rather comprehensive set of evidence-based clinical practice guidelines for the pharmacological management of obesity, published in the Journal of Clinical Endocrinology and Metabolism.
The recommendations in the 21-page document follow the rather rigorous Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group (from 0 to 4 stars) and goes beyond just evaluating the evidence in favour of pharmacological treatment of obesity itself but also for the pharmacological treatment of overweight and obese individuals presenting other medical conditions.
Here are the (in my opinion) most important recommendations from this document:
1) While diet, exercise and behavioural interventions are recommended in all patients with obesity,
“Drugs may amplify adherence to behavior change and may improve physical functioning such that increased physical activity is easier in those who cannot exercise initially. Patients who have a history of being unable to successfully lose and maintain weight and who meet label indications are candidates for weight loss medications.(****)”
2) “If a patient’s response to a weight loss medication is deemed effective (weight loss > 5% of body weight at 3 mo) and safe, we recommend that the medication be continued. If deemed ineffective (weight loss < 5% at 3 mo) or if there are safety or tolerability issues at any time, we recommend that the medication be discontinued and alternative medications or referral for alternative treatment approaches be considered. (****)”
3) “If medication for chronic obesity management is prescribed as adjunctive therapy to comprehensive life- style intervention, we suggest initiating therapy with dose escalation based on efficacy and tolerability to the recommended dose and not exceeding the upper approved dose boundaries. (**)”
The guidelines also make specific recommendations for the pharmacological treatment of overweight and obese individuals presenting with a wide range of other medical issues, including 2 diabetes mellitus (T2DM), cardiovascular disease, psychiatric illness, epilepsy, rheumatoid arthritis, COPD, HIV/AIDS and allergies.
For example:
“In patients with T2DM who are overweight or obese, we suggest the use of antidiabetic medications that have additional actions to promote weight loss (such as glucagon-like peptide-1 [GLP-1] analogs or sodium-glu- cose-linked transporter-2 [SGLT-2] inhibitors), in addi- tion to the first-line agent for T2DM and obesity, metformin. (***)”
The guidelines also discuss the pros and cons of the anti-obesity medications currently available in the US (phentermine, orlistat, phentermine/topiramate, lorcaserin, buproprion/naltrexone, and liraglutide), which we can only hope will soon also become available to patients outside the US.
The entire document is available here.
@DrSharma
Edmonton, AB
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