DEAR MAYO CLINIC: It seems like no matter what I do, I can’t lose weight. Most of my family members struggle with their weight too. Do our genetics play a part in this?
ANSWER: It’s important to understand that we are all unique and gain weight for many different reasons. When trying to understand weight gain and why some of us have difficulty losing weight, there are factors such as gut and brain connections, how we control our sensation of hunger and fullness and how long we stay full. Over a decade of studies at Mayo Clinic have helped identify characteristics that can be associated with groups of people called obesity phenotypes.
Each phenotype has a single genetic predisposition (an increased likelihood of developing obesity based on a person’s genetic makeup) and interacts differently with their environment. In many environments we see today, there is an excess of food, and we’re less active than before. Some people may feel hungry between meals, while others only have one big meal a day — our genetics drives this. Your genetic makeup determines which phenotype you’re going to have. These phenotypes can help guide treatment for weight loss. Each of these genetic phenotypes, or genotypes, identifies the type of obesity and which medication would work best.
The first phenotype is what we call “hungry brain.” These patients start eating and don’t feel full even after consuming large meals with second and third helpings. Usually, this runs in families. The other phenotype is what we call “hungry gut.” These patients start eating and feel full after their usual portion, but the gut does not send those signals to the brain. Because of that, they feel hungry between meals. Signals from the gut to the brain are hormones, such as glucagon-like peptide-1 (GLP-1). Semaglutide medications such as Wegovy, Ozempic and Rybelsus work on behalf of the GLP-1 hormone. They connect between the gut and the brain, and they signal to the brain that you’re full.
Patients who have emotional hunger are another group. Whether having a good or bad day, these patients look to cope with life by eating food. The fourth group is patients with a “slow burn” or abnormal metabolism where the body does not burn all the calories they consume.
Looking at these four phenotypes can help individualize obesity therapy. How genes correlate with an obesity phenotype can help determine which medications should be prescribed. Each of us also should have a unique diet approach based on our genotype and phenotype. Many diets have mainly focused on obesity-related complications, such as managing Type 2 diabetes or preventing heart risk, but none have been customized to phenotypes. The concept of the phenotype-tailored diet came from multiple studies that showed metabolic benefits during and after the diet plan began. These findings were then matched to each phenotype to define recommended diets.
At Mayo Clinic, we work closely with our colleagues in bariatric surgery through endoscopic procedures to find out, based on our genetics, how we can identify who will be the most responsive to each course of action. We want to bring precision medicine as we have for any other disease, and I think it’s time we do the same for obesity. — Andres Acosta, M.D., Ph.D., Bariatrician, Gastroenterologist, Mayo Clinic, Rochester, Minnesota
(Mayo Clinic Q & A is an educational resource and doesn’t replace regular medical care. For more information, visit www.mayoclinic.org.)
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