The innovation: Single-cell RNA sequencing of donated adipose tissue

In recent years, the medical community has made insights that overturn long-standing assumptions about obesity. For example, we’re realizing that obesity is probably not a single disease and that there are many nuances in how it affects people. Bethany Cartwright, M.D., Ph.D., Pediatrician at Children’s Health℠ and Assistant Instructor at UT Southwestern, is doing some of the first studies to explore these nuances in children with obesity.

Dr. Cartwright is performing novel research that focuses on single-cell RNA sequencing of pediatric fat, also known as adipose tissue. By capturing the gene expression profile of individual cells within a sample, she aims to characterize the cellular subtypes present and explore their relationships with disease. She’s also building one of the nation’s first biorepositories of pediatric adipose tissue.

“The goal is to map out an atlas of what these cellular subtypes look like in children, and how they change as a child grows up, to help fuel personalized medicine approaches,” Dr. Cartwright says. 

 

The big picture: Forging new ground in pediatric obesity research

Since summer 2021, Dr. Cartwright has been studying donated tissue samples. An important, preliminary finding based on adipose tissue collected from an initial cohort of 12 teenagers shows that the tissue contains more endothelial cells, which line blood vessels, than are present in adult adipose tissue.

"We are really excited about this finding because it shows for the first time that the cellular makeup of pediatric adipose is fundamentally different from that of adults,” Dr. Cartwright says. She would like to study whether the differences in the tissue between adults and children could help explain why childhood-onset obesity confers higher risk of diabetes and other complications than adult-onset.

In future experiments, Dr. Cartwright also plans to explore the differences between children of different ages and sizes, which may lead to therapies for teenagers and adults with obesity. Current medical interventions such as weight-loss surgery and weight management medications offer some hope against obesity. However, they are only available for adolescents, not younger children. And insurance, particularly Medicaid, often doesn’t cover them.

A key problem with treatments for obesity both in children and adults is that responses are highly variable between individuals. “There is a call in the obesity medicine field to learn more about the biological differences between people with different stages of disease and different responses to treatment,” Dr. Cartwright says.

Key details: Building a unique biorepository

Dr. Cartwright is freezing the samples she collects and creating one of the first biorepositories for adipose tissue. She is working closely with Faisal Qureshi, M.D., Pediatric Surgeon at Children’s Health and Associate Professor at UT Southwestern, and the entire surgery team. They talk with patients who are going to have surgery about Dr. Cartwright’s work, help her consent the patients and their families, and work with her team to collect tissue samples in the operating room.

So far, the biorepository contains samples from 36 patients, ranging in age from 7 months to 19 years. Dr. Cartwright thinks the biorepository will be an invaluable resource for researchers at Children’s Health and other institutions.

For example, a researcher may discover a gene they think is associated with the development of obesity or with health outcomes related to it. They could obtain tissues from the biorepository to explore how the expression of that gene may vary based on patients’ BMI, comorbidities, age, race and other characteristics.

To date, very little is known about the reasons certain children develop obesity and obesity-related diseases. But it’s clear that children with obesity are at higher risk of poor lifelong health.

“If your weight gain begins in childhood, you’re more likely to develop those complications than if you gain weight as an adult. You’re also more likely to have worse diabetes-related outcomes in terms of poor control of blood sugar and eye and kidney disease,” Dr. Cartwright says.

Why Children’s Health: Changing the game in pediatric obesity care and research

Dr. Cartwright didn’t fully appreciate how much the care of children with obesity needed to improve until she started seeing patients in the COACH Program for Child Obesity and Weight Management at Children’s Health.

“I still find it staggering how much suffering some of my patients go through, either because of health problems or the way they’re treated by other doctors or the outside world,” Dr. Cartwright says. 

Dr. Cartwright takes a personalized and supportive approach when she talks with children and their families. She asks them about their weight goals and helps them make realistic plans for achieving those goals and preventing diabetes and other conditions. She shares what she has learned with medical students and trainees at Children’s Health and UT Southwestern.

Although Dr. Cartwright says that clinical care of children with obesity is generally improving, the field of pediatric obesity research is lagging. There hasn’t even been a published study on adipose tissue from children with obesity that looks at the single-cell level – although Dr. Cartwright’s work and the biorepository will hopefully soon change that.

She feels very fortunate that she can combine her two passions – medicine and scientific discovery – through her research and care for patients in the COACH program.

“There are a host of unanswered questions right now in pediatric obesity research that are ripe for answering,” she says.

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