Biology over Willpower? – Response to The Wall Street Journal

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I came across an article in The Wall Street Journal (WSJ) last week which had an intriguing title – Ozempic settles the Obesity Debate: It’s Biology over Willpower. I figured it might be a click-bait type of article, but I was surprised to see that the author seems to be pushing the narrative that anyone who is trying to lose weight but is failing to do so, should jump on these brand-new, lacking long-term evidence, GLP-1 agonist drugs like Ozempic, Wegovy and Mounjaro.

Don’t get me wrong, with 42% of U.S. adults being obese, and based on study results and user reports, these drugs can work wonders for many obese individuals, however writing an article like this with little to no mention of the roles genetics, environment, lifestyle, and diet play in obesity is irresponsible – and likely the result of big pharma being behind media coverage like such.

“However, portraying weight loss solely as a matter of adjusting a set-point might inadvertently promote a more passive attitude toward one’s health…”

The main argument being made in the WSJ article is that our bodies all have different set-points. It is true, our body tends to like being in homeostasis (maintaining stability while adjusting to conditions that are best for survival). However, portraying weight loss solely as a matter of adjusting a set-point might inadvertently promote a more passive attitude toward one’s health. In other words, taking a GLP-1 receptor agonist will enable you to lose your extra pounds and you don’t even have to change your lifestyle and diet. Just like the ever-increasing number of patients who are put on statins to lower their blood lipids, without changing their diet or their exercise level. This is the perfect scenario for the pharmaceutical industry who loves to see more millions of people becoming dependent on these drugs.

The article seems to ignore the fact that with lifestyle change, such as changing our diet (i.e. shifting from an ultra-processed, fast food-type diet to one of minimally processed whole foods and little sugar) and increasing physical activity, we are able to change our set-points which are programmed into our brain gut microbiome system.

Like everything on planet Earth, our bodies follow the laws of thermodynamics. If we eat 2200 calories in a day and burn 2200 calories through our basal metabolic rate (calories we burn doing nothing), physical activity and the thermic effect of feeding (the energy it takes for your body to digest, absorb and metabolize the food you eat), we should be the same weight the next day, give or take some due to hydration, differences in metabolism, etc. By shifting our diet to whole foods, we are minimizing the empty-calorie foods we eat (high calorie foods full of fat and sugar with minimal nutrients, i.e. donuts, soda, candy bars), while also receiving the vital nutrients we need, helping tell our body to feel full for longer. Now, it is important to note that this may be easier for some than others due to environmental factors such as living in a food desert (fewer grocery stores, many corner stores and fast-food restaurants) or living with family or friends who consume unhealthy foods (obesogenic environment).

“It ignores the bidirectional interactions between the brain, the gut and its microbiome which play such a crucial role in the generation of food related sensations, such as hunger, satiety and food aversion.”

The WSJ article highlights the importance of the brain, being the “chief chemist” in controlling our appetite and weight. Without a doubt, the brain, in particular the centers that regulate hunger and satiety does play a very important role here but the article is oversimplifying a much more complex situation. It ignores the bidirectional interactions between the brain, the gut and its microbiome which play such a crucial role in the generation of food related sensations, such as hunger, satiety and food aversion. GLP1 has long been known to be produced, stored and released from specialized cells in our gut, called enteroendocrine cells. GLP release is caused not only by ingested protein and sugars, but also by microbial metabolites such as short chain fatty acids generated from complex carbohydrates, e.g. plant based fiber. GLP reaches the brain via the vagus nerve and the bloodstream and activates GLP-1 receptors in the hypothalamus generating a sensation of fullness and motivation to stop eating.

Studies have shown that those who regularly consume foods high in calories (especially high in added sugar/empty calories) can result in a downregulation of the GLP-1 receptor in the hypothalamus, compromise the brain’s homeostatic functions, reducing its ability to regulate calorie intake and switch to a pattern of hedonic eating. This switch from eating what the body needs to food consumption based on pleasure can lead to overeating and weight gain. If you know about how the brain’s reward network functions, this makes total sense. Foods that cause immense pleasure (dopamine release) such as those high in sugar and fat will cause you to feel good and less stressed in the short term, but desensitizing your dopamine receptors as a result. Once the feeling goes away, your brain will be seeking that same feeling, causing you to further seek out foods which replicate it. It’s a vicious cycle.

“…we also aren’t sure of the long-term consequences of these drugs as they are newly approved for human consumption.”

There is no question, that this new category of drugs do work and have been highly effective in the short term in many cases. However, they are not for everyone. Importantly, we aren’t sure of the long-term consequences of taking these medicines as they are newly approved for human consumption. For example, will long term use of these drugs lead to a desensitization of the GLP-1 receptor, making it even less sensitive to physiologically released GLP? Will individuals who have successfully lost weight on these drugs be able to keep their weight down at a new set point once they stop taking the drugs, or will there be the well-known Yo-yo effect, with weight rebounding even above the starting weight before taking the medication. If that is the case, will this require lifelong use of the drug to keep body weight down?

Ozempic and its counterparts do offer hope for individuals unsuccessfully struggling with obesity, but I disagree that it should be a first-line defense. The article I’m referencing oversimplifies obesity, and it should be approached in a more holistic view – taking into account the role of the brain gut microbiome system, genetics, lifestyle and individual responsibility. As we’ve written about extensively here, changing your diet to that of one that nourishes your body (keeping your gut microbes in mind) and implementing physical exercise into your lifestyle are ways which you can lose the weight and keep it off without becoming dependent on an expensive drug.

E. Dylan Mayer Dylan is a graduate from the University of Colorado at Boulder, with a major in Neuroscience and minor in Business. He has also recently completed his M.S. in Human Nutrition at Columbia University.

This article was reviewed and approved by Emeran Mayer, MD