Study links higher blood levels of the “hunger hormone” ghrelin to subsequent weight gain in individuals with anorexia nervosa

BOSTON – In a study that included adolescent girls and young women with anorexia nervosa (AN) and healthy controls, participants with AN with higher blood levels of ghrelin —a hormone produced primarily by the stomach that has been shown to promote food intake and weight gain in animal models—were more likely to gain weight over the following 18 months. Higher baseline levels of ghrelin were not associated with weight gain in healthy controls.

The research, which was led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), and was published in JAMA Network Open, provides important information about body weight regulation in humans, which could potentially benefit patients with eating disorders.

To study the role of ghrelin in weight balance, lead and corresponding author Youngjung Rachel Kim, MD, PhD, a psychiatrist physician-investigator in psychiatry at MGH and an instructor in Psychiatry at Harvard Medical School, and her colleagues measured blood levels of the hormone in 68 girls and women aged 10 to 22 years: 35 with anorexia nervosa and 33 without.

“Our approach was unique as it was the first to test the association between baseline ghrelin and prospective body weight change in individuals with anorexia nervosa,” says Kim.

At the start of the study, participants with anorexia nervosa were slightly older, had lower body mass index, and had higher circulating ghrelin levels compared with controls. Higher ghrelin levels at baseline were linked with greater weight gain at 9- and 18-month follow-up visits for participants with AN.

This is the first study to the team’s knowledge that reports an association between ghrelin levels and weight trajectory in individuals older than infants. Prior studies have consistently demonstrated a lack of association between ghrelin and weigh trajectory, despite the hormone’s role in stimulating food intake.

“Our study adds to our understanding of body weight regulation in humans,” says Kim. “Anorexia nervosa is a debilitating illness with one of the highest mortality rates in psychiatry and there are no FDA-approved treatments to date. So, we need more studies to confirm this novel finding and to evaluate whether ghrelin signaling plays a direct role in weight regulation in anorexia nervosa. A better understanding of ghrelin biology could potentially help in developing new treatments for this vulnerable patient population.” She notes that investigations of ghrelin signaling at the cellular level that may be specific to individuals with anorexia nervosa are warranted.

Additional study authors include Meghan S. Lauze, BS; Meghan Slattery, MSN; Roy H. Perlis, MD, MSc; Laura M. Holsen, PhD; Lauren Breithaupt, PhD; Casey M. Stern BA; Maurizio Fava, MD; Jennifer J. Thomas, PhD; Elizabeth A. Lawson, MD*; Madhusmita Misra, MD, MPH*; and Kamryn T. Eddy, PhD* (*co–senior authors).

This work was supported by the National Institute of Mental Health, the National Institute of Diabetes and Digestive and Kidney Diseases, the Brain Behavior Research Foundation, the Phyllis & Jerome Lyle Rappaport Foundation, and the MGH Department of Psychiatry.

 

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.