Leptin Levels High in Adults Abused as Children

Becky McCall

April 01, 2014

Significant neglect or abuse during childhood adversely affects levels of the hormones leptin and irisin, suggesting a link between adversity in early years and metabolic disorders later in life, according to a new study.

This is the first known report of early-life adversity influencing levels of adipomyokines (hormones released from adipose tissue) in adult life, say the investigators. It adds to the growing body of data regarding the potential impact of early-life adversity on obesity, diabetes, and metabolism in later life.

The research is published online in the Journal of Clinical Endocrinology & Metabolism.

In an interview with Medscape Medical News, authorsKyoung Eun Joung, MD, and her colleague Christos Mantzoros, MD, from Beth Israel Deaconess Medical Center and the VA Boston Healthcare System, affiliated with Harvard Medical School, Boston, Massachusetts, said they wanted to build on their previous work, which found an association between early-life adversity and obesity and metabolic syndrome. In particular, they wanted to shed light on the mechanisms at play.

Raised Leptin and Irisin in High-Adversity Group

The cross-sectional study recruited 95 adults aged 35 to 56 years from the general population of the greater Boston area via advertisements, including newspapers, flyers, and radio. Information on early-life adversity and psychosocial measurements was collected, and each participant was assigned a score based on the severity of the abuse or neglect experienced during childhood.

A detailed medication history including psychiatric drugs — such as antidepressants, psychotropic medications, and anxiolytics — was taken.

The researchers divided the participants into 3 groups and then compared hormone levels in people with the highest adversity scores with those of the other two-thirds of the participants. Circulating levels of the hormones adiponectin, irisin, and leptin as well as C-reactive protein (adipomyokines) were measured from venous blood samples.

The group with severe early-life adversity, the top third, had significantly higher levels of leptin and irisin compared with the other 2 tertiles, even after adjustment for demographic variables, body mass index (BMI), physical activity, diet, and mental-health status.

Higher levels of C-reactive protein and lower adiponectin were also found in the high-adversity group compared with the other 2 tertiles, although Dr. Joung explained that these findings were nullified after adjustment for age, gender, and race, indicating that the effect of adversity may be mediated by some interaction with these factors on the hormonal influences.

"Participants in the group who had experienced the highest adversity showed the greatest difference with the other 2 groups, indicating that there is an inflection point," remarked Dr. Joung. "Somehow the upper third of the population with higher adversity suffers disproportionally more abnormalities."

Possible Mechanisms: HPA Axis Involved?

Leptin is a hormone that reduces appetite and is an important determinant in the development of obesity and metabolic syndrome; it is also known for its strong correlation with BMI and fat mass, the authors explain.

In their paper, they point out that a possible mechanism for their findings could be stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by stress, which increases the production of glucocorticoids.

In turn, glucocorticoids have been shown to stimulate the release of leptin from adipose tissue and also contribute to the development of leptin resistance at the same time. For this reason, the authors suggest that "leptin could be a mediator of the effect of childhood adversity on obesity via alteration of the HPA axis."

Dr. Joung further elucidated the potential role of glucocorticoids in the sequence of events that might link stress to impaired hormonal levels and obesity. "Levels of cortisol [glucocorticoid] in the human circulation are lowest early in the morning and rise upon waking. Children exposed to adversity show a blunted cortisol-awakening response," she explained.

She pointed out that interventions aimed at helping childhood sufferers of abuse have involved alteration of the HPA axis, as represented by control of abnormal cortisol levels.

"Cortisol could be normalized via interventions such as home visits, psychotherapy, and psychoeducational parenting, and this has been tried by various groups. Although not all the studies gave consistently positive results, many of them reported successful change of cortisol-awakening response."

Looking ahead, Dr. Joung said, "We would also like to see if specific interventions could alter the hormonal profile, such as making a difference in leptin and irisin levels, too. But for a conclusive answer regarding causality between early-life adversity and adipomyokines, future well-controlled studies are needed."

The authors have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online March 20, 2014. Abstract

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