‘Phenotype-informed interventions’ hold key to treat obesity, break weight cycling
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Although an estimated 45 million Americans will try a diet each year, roughly 90% of people who lose weight end up gaining it back.
This perpetual diet, weight loss and weight gain cycle can be discouraging for people who want to successfully lose weight and improve their health, but there are significant metabolic adaptations at play that influence a person’s ability to maintain their weight loss.
Obesity is a disease of energy balance dysregulation that results in the storage of excess calories as fat. Energy balance relies on energy intake and expenditure; two processes tightly regulated by humoral and neuronal signals in response to internal and external cues. Every time someone tries to lose weight, regardless of the specific diet, they are eating a reduced-calorie diet. They initially experience increased hunger with more food cravings, and they will likely feel a steep drop in energy. If you’ve ever tried a diet, you know what I’m talking about.
Most professional societies recommend a caloric deficit coupled with moderately intense physical activity for weight loss, but studies comparing different diets do not document the superiority of any specific diet for weight loss and long-term benefit with any intervention depending on diet adherence.
Diet interventions based on macronutrients, genetics or meal timing have shown no benefit compared to standard treatment. Diet interventions mainly focus on obesity-related complications — managing or preventing type 2 diabetes, cardiovascular risk or hypertension — but none are tailored to the underlying pathophysiological and behavioral abnormalities identified in patients with obesity.
‘Simple Diet and Exercise’ Fails Most Patients
A caloric-deficit diet results in a metabolic adaptation that occurs in response to decreasing a body’s metabolic rate, or the number of calories an individual needs to survive and keep their basic bodily functions happy and working. Thus, the body’s metabolism slows down and fewer calories need to be consumed in order to maintain weight loss. While this metabolic adaptation once served to keep people alive during prehistoric food scarcity, it’s the same reason why a simple diet and exercise approach fails the majority of people in modern times.
Taking this adaptation into consideration, we have developed an understanding of obesity as four different diseases with unique phenotypes that impact a person’s ability to successfully lose weight. Phenotyping classifies a person’s type of obesity based on their personal biological mechanisms. By understanding how the four different phenotypes influence a person’s weight gain and limit their ability to lose weight, a physician can tailor treatment to a patient’s unique needs.
Research from the Mayo Clinic has shown that these phenotype-tailored strategies can produce significant weight loss in adults with obesity. Our team has stratified obesity into these four phenotypes:
- Hungry brain: This group suffers from not feeling satiated, regardless of how much food they have consumed, and typically eat more than other people to feel full.
- Hungry gut: Are you hungry again, even though you just ate a full meal an hour ago? This group suffers from abnormal postprandial satiety.
- Emotional hunger: Feeling sad? Time to eat. Happy? Let’s celebrate with food. This group typically lacks control when eating in response to their emotions and they suffer from hedonic eating.
- Slow burn: This group might have their exercise and food goals dialed in, but the scale doesn’t budge. They suffer from a slow metabolism, also known as abnormal resting energy expenditure.
We have determined that at least 85% of patients with obesity have one of these four phenotypes. When a physician determines which phenotype is influencing a patient’s behavior, they can make a more informed decision about the interventions and treatments that will work best for that patient.
Tailoring Intervention to Type
In a 12-week study published in eClinical Medicine, 165 patients were divided into 2 groups: one group of patients followed a standard lifestyle intervention that included adhering to a Mediterranean diet with a 500-calorie deficit, 150 minutes of moderate exercise per week and a recommendation to reach 10k steps daily, whereas the other group was given a phenotype-tailored lifestyle intervention:
- Participants with the ‘hungry brain’ phenotype were instructed to restrict their meals to one or two per day with a filling, high-fiber diet.
- The ‘hungry gut’ phenotype group was instructed to have three meals per day with a pre-meal protein supplement.
- The ‘emotional eating’ group ate a Mayo Clinic diet, cut down on snacking, participated in behavioral group therapy with clinical health psychologists and checked in weekly with their wellness coach.
- The ‘slow burn’ group followed a Mayo Clinic diet combined with a post-workout protein drink. They were directed to do at least 30 minutes of high-intensity interval training four to five times per week and check in weekly with their physical therapist.
According to study results, patients who followed the diet and exercise program tailored to their specific phenotype saw twice as much weight loss as patients who followed the standard lifestyle recommendations. They saw benefits to their metabolic and physiological adaptations associated with weight gain, and had a greater decrease in waist circumference, fat mass, gastric emptying, anxiety score and triglycerides level.
While more studies are needed, these findings suggest that phenotype-informed interventions can benefit not only patients struggling with obesity but those who are overweight and get caught in the diet, weight loss and weight gain cycle year after year.
The outcome of this 12-week study underscores why ‘one-size-fits-all’ treatments for obesity don’t work for many patients long-term. Obesity is a multifactorial disease that requires precision medicine to target treatments for patients in a way that yields long-term success.
References:
- Acosta A, et al. Obesity (Silver Spring). 2021;doi:10.1002/oby.23120.
- Cifuentes L, et al. EClinicalMedicine. 2023;doi:10.1016/j.eclinm.2023.101923.
For more information:
Andres Acosta, MD, PhD, is a consultant and assistant professor of medicine in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minnesota. He also co-founded Phenomix Sciences.
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