Obesity doesn’t look the same at age 15 as it does at age 45 and Duke University School of Medicine researchers are learning why.
A study published in the Journal of Clinical Investigation showed teenagers retain a degree of metabolic flexibility that’s largely lost in adulthood. The study suggests that the way teenage bodies respond to excess weight is fundamentally different and potentially more reversible.
By showing that obesity’s biology changes with age, the discovery points to a potential window when the metabolic damage linked to obesity can be halted, or even reversed, before it becomes a lasting health burden.
“For a long time, medicine has tended to treat adolescents as little adults,” said John Rawls, PhD, a professor of molecular genetics and microbiology and member of the Duke Microbiome Center. “But teenagers are still growing, building muscle and bone, and using energy in ways that are very different from adults. We wanted to understand how those differences shape obesity.”
Nearly 1 in 5 U.S. children has obesity, a condition associated with higher risk for heart disease, diabetes, asthma, and some cancers later in life.
Without intervention, most children with obesity will continue to have obesity into adulthood, said study co-author Sarah Armstrong, MD, a pediatrician and medical weight management specialist at Duke Health.
The change from adolescence to adults happens in late teens to early 20s for women and early-to-mid 20s for men.
But researchers are increasingly asking when those risks become biologically embedded and whether adolescence offers a chance to change course.
The microbiome tells a different story in teens
The Duke team focused on two systems often linked to obesity: the gut microbiome which is the community of microbes living in the digestive tract, and the metabolome, the collection of chemicals produced as the body and microbiome process food and energy.
First, using gut microbes collected from 287 teenagers in the Pediatric Obesity Microbiome and Metabolism Study, they confirmed that teens with obesity have microbiomes that differ compositionally from those of teens at a healthy weight.
Next, Jessica McCann, PhD, a senior research associate in molecular genetics and microbiology, transplanted microbiome samples from adolescents with and without obesity into germ-free mice.
Unlike what researchers often see in adult obesity studies, the mice did not gain extra weight after receiving microbiota from adolescents with obesity.
The findings indicate that while obesity-related differences in the microbiome are beginning to emerge during adolescence, those microbes may not be driving disease the waythey do in adults.
“This suggests there’s a developmental window in which the microbiome becomes involved in obesity,” McCann said. “The relationship between the host and the microbiome may still be developing during adolescence, which means there may be an opportunity to change its trajectory.”
Warning signs appear, but so does resilience
Working in collaboration with the Duke Molecular Physiology Institute, the research team also found differences in how adolescents process nutrients. Adults with obesity often have elevated levels of branched-chain amino acids, as well as related compounds called branched-chain keto acids (BCKA), which are linked with insulin resistance and Type 2 diabetes.
The adolescents showed a different pattern. While branched-chain amino acids were elevated, BCKA levels remained relatively low.
The warning signs are there, McCann said, but teens’ bodies still appear capable of adapting to the metabolic strain of excess weight. “The metabolome is showing early signs of disease progression, but it’s also showing evidence of adaptive plasticity.”
At this stage they may be more responsive to weight management through diet, medication or microbiome-based therapies.
“The evidence increasingly supports intervening as early as possible,” said Armstrong, a professor of pediatrics at Duke.
Researchers hope the work would eventually lead to more personalized obesity treatments, using a child’s microbiome or metabolic profile, to help determine which weight loss therapies are most likely to succeed.
The study was supported by the American Heart Association and the National Institute of Diabetes and Digestive and Kidney Diseases.