ORLANDO—Brown fat burns energy; white fat settles in.

That truth represents a major finding in a recent study concerning the impact of orexin in weight control at the Sanford-Burnham Institute for Medical Research at Lake Nona.

With that important tidbit of information come more questions:

Who has brown fat and why?

Who has white fat and can it be converted to brown fat?

Whatever the answers are, rest assured, how orexin works individually will impact the way weight control is addressed.

“Appetite suppressant drugs on the market have side effects—from psychological to cardiovascular—and to find a way to increase energy so that appetite suppression isn’t the only answer to weight loss would be remarkable,” said Devanjan Sikder, DVM, PhD, an assistant professor at Sanford-Burnham Medical Research Institute’s Diabetes and Obesity Research Center, located in Orlando’s Medical City at Lake Nona. “It’s a paradigm shift of treatment methods for obesity.”

Orexin Origins

Years ago, Sikder, a molecular biologist, had been studying how metabolism impacts sleep and weight control when he stumbled across some very interesting research involving orexin.

Orexin—a hypothalamic neuropeptide—regulates metabolism, sleep patterns and feeding behavior, and the role that hunger plays in the regulation of fat metabolism and insulin secretion.

Then he began wondering: Why do some people have a lower metabolic rate while others put on weight much more quickly?

“We all know family and friends who are lean and manage to eat what they want, while some of us eat a little bit and accumulate a lot,” said Sikder. “The process of weight gain that’s not linked to overconsumption of food has been noted, but remains an enigma in the medical community. Medical professionals believe it may be linked to differences in physical activity. For example, some of us sit quietly; others are more jittery or restless. This may explain part of it but we now have more of the story than previously recognized.”

Fast Forward

In the last three or four years, it’s been recognized that the activity of brown fat correlates with leanness. Brown fat, once thought be vestigial in adults, appears to dictate whether one is going to burn or store the extra calories consumed .  “The level of activity of this tissue is regulated by orexin. Brown fat stops functioning if this hormone isn’t present. Without orexin, your ability to burn extra calories is compromised, which leads to obesity,” explained Sikder.

In a study recently published in Cell Metabolism, Sikder, senior author of the study, and his team, including postdoctoral researchers Dyan Sellayah, PhD, and Preeti Bharaj, PhD, looked at mice genetically engineered to lack orexin. These mice weighed more than their normal counterparts, but they actually ate less, suggesting that overconsumption wasn’t the cause of their obesity. Rather, the orexin-deficient mice lacked diet-induced thermogenesis. These orexin-deficient mice failed to dissipate the extra calories as heat the way that normal mice (and people) do. Instead, they stored that energy as fat.

This finding prompted the team to look at the mice’s brown fat—a source of thermogenesis. They found that brown fat in mice lacking orexin didn’t develop properly at the embryonic stage. This shortage had lasting effects on energy expenditure and weight even in adulthood.

“Brown fat is formed at the later stage in pregnancy,” he said. “When there’s insufficient orexin in the placenta during that stage of pregnancy, babies are born with a condition that, later in life, will predispose them to obesity.”

Researchers also gave the defective mice more orexin. With the hormone present, brown fat developed properly before birth and continued to be active into adulthood. What’s more, adding orexin to stem cells in a laboratory dish caused them to mature into brown fat cells, creating more of this fat-burning engine.

And now …

Until recently, investigators haven’t considered that dysfunctional brown fat could underlie subsequent obesity in adults.

“Our findings could prompt a change in thinking regarding causes of obesity,” said Sikder.

Could low blood orexin be the culprit in development of obesity? In collaboration with Florida Hospital, Sanford-Burnham researchers are measuring plasma levels of orexin in obese subjects.

“We’re now taking the next steps in determining how orexin—or a chemical that has the same effect—might be used in humans to therapeutically prevent or treat obesity,” said Sikder. “That’s our goal within the next two years.”

According to the Centers for Disease Control and Prevention, about one-third of U.S. adults (33.8 percent) are obese. As a person becomes overweight or obese, he is at increased risk for type 2 diabetes, coronary heart disease, stroke, and certain cancers.

Preventing Childhood Obesity

Nemours expands initiative in Central Florida with Winter Park Health Foundation grant

Nemours Children’s Hospital and the Winter Park Health Foundation (WPHF), along with a little help from 50 squirmy preschoolers, launched a childhood obesity prevention initiative before the school holiday break in Eatonville, Maitland and Winter Park child care settings, with a focus of growing a healthier generation.

A $50,000 foundation grant made possible the expansion of this unique initiative into 14 child care centers in Winter Park, Eatonville and Maitland.

“Nemours is honored to have the support of the Winter Park Health Foundation in this effort to combat childhood obesity”, said Roger Oxendale, CEO of Nemours Children’s Hospital. “Nemours has a history of working beyond the walls of our clinics and hospital to improve the health of children and with this investment. We’ll be able to conduct more of that important work.”

Nemours associates will train child care providers on two programs: Nemours Healthy Habits for Life and the Nemours prescription for a healthy lifestyle: 5-2-1-Almost None. Healthy Habits helps children learn about “sometimes” and “anytime” food, eating the colors of the rainbow, and incorporating movement into play activity. The 5-2-1-Almost None Program focuses on getting children moving and keeping them active, reducing television screen time, making nutrition fun and limiting sugary beverages and treats.

Training is scheduled to begin this month.

Developed by Nemours and Sesame Workshop, Healthy Habits for Life is a resource kit to assist child care providers with the education and tools they need to promote healthy eating and active living in the child care setting that has proved to be successful in introducing the components of a healthy lifestyle to pre-school children.

“The best way to help children make healthy choices in later life is to practice them early,” said Nemours’ Lloyd Werk, MD, director of the Florida Prevention Initiative.

Other child care centers in Central Florida already have received training; the mission is to spread it to others and saturate the area. “Our goal is to help grow a healthier generation.”

The initiative is a natural extension of the ongoing work of the foundation, which has offered free school-based health and wellness services in a dozen public schools in Winter Park, Eatonville and Maitland for more than a decade. The participating child care centers channel students into these same schools.

“The programs we’ve offered are designed to help students become as healthy and academically productive as possible and are based on the belief that healthy kids make better students, and better students make healthy communities,” said WPHF CEO Patricia Maddox. “Nemours’ programs complement all we’re doing in elementary, middle and high school. You’re never too young to learn the benefits of active living and healthy eating, and we hope these youngsters will lessons through life.”

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