Leptin in embryonic development may contribute to type 2 diabetes in children

John Murphy, MDLinx | March 30, 2016

The presence of the hormone leptin during a critical period of embryonic growth can lead to long-term impairments in glucose homeostasis, according to a study published online March 24, 2016 in the journal Cell Reports. This finding may help explain the origin of type 2 diabetes in children of obese mothers, who have high levels of leptin, the researchers noted.


Type 2 diabetes obesity study of leptin at Children’s Hospital Los Angeles

The fat cell hormone leptin can permanently decrease the prenatal innervation of the pancreas (as seen in this islet), which then alters glucose homeostasis. (Image: Children’s Hospital Los Angeles)

Leptin is known to regulate the activity of the autonomic nervous system during adulthood, but whether leptin is involved during the embryonic development of the autonomic nervous system—creating neural connections between the brain and pancreas—hasn’t been known.

In this study, scientists at The Saban Research Institute of Children’s Hospital Los Angeles (CHLA), in Los Angeles, CA, investigated the development of parasympathetic innervation of the pancreas. They reasoned that if leptin is a critical regulator of the cholinergic innervation of the pancreas, then exposing embryos to leptin should change cholinergic nerve fiber density.

To test this, they injected a single dose of leptin directly into the brain of mouse embryos during mid-gestation. They found that the leptin permanently decreased innervation of the pancreas, which altered the regulation of glucose. This effect continued into adulthood.

“We showed that exposure of the embryonic mouse brain to leptin during a key developmental period resulted in permanent alternations in the growth of neurons from the brain stem to the pancreas, resulting in long-term disturbances to the balance of insulin levels in the adult mouse,” said Sebastien G. Bouret, PhD, researcher in the developmental neuroscience program at CHLA.

“This breakdown in communication from the brain to the pancreas resulted in impaired glucose homeostasis in the adult mouse,” Dr. Bouret said. “This study reveals an unanticipated regulatory role for the leptin hormone known to be produced by fat cells. Because babies of obese moms have high levels of leptin, it might put them at a higher risk for type 2 diabetes and obesity.”

Ameliorating or even reversing this metabolic “malprogramming” will require further research into the role of leptin and metabolic diseases, the researchers wrote.