The Zigman Lab is composed of Dr. Zigman and several postdoctoral fellows, a graduate student, and two research scientists. Our work spans the fields of molecular endocrinology, behavioral neuroscience, and neuroanatomy and includes animal, human and cell culture experiments. We use a variety of methods and techniques to test our hypotheses.

The Zigman Lab is interested in the peptide hormone ghrelin, and in particular how it influences various eating behaviors (eating when hungry, eating for pleasure and stress-induced eating), body weight, the body’s responses to gastric bypass surgery and stress, blood glucose, reward behaviors, and mood. We also investigate ghrelin secretion and also the relationship of ghrelin cells to other endocrine cells in the gastrointestinal tract.

Ghrelin cell physiology
Examples of some techniques used to study ghrelin cell physiology in the Zigman lab. Left Slide: Endogenous GFP fluorescence visualized in the stomach lining of a ghrelin-GFP reporter mouse. Right Slide: Ghrelin mRNA expression visualized in mouse gastric mucosa by in situ hybridization histochemistry.

Ghrelin is secreted primarily by distinct ghrelin cells located in the lining of the stomach and intestine, however little is known regarding the exact mechanisms that control ghrelin biosynthesis and secretion.

Ghrelin acts by binding to the growth hormone secretagogue receptor (GHSR; ghrelin receptor), which is a G-protein coupled receptor located in numerous brain sites and peripheral organs.

ghrelin receptor mRNA epression
Thin coronal section of a rat brain indicating ghrelin receptor mRNA expression in the hypothalamus and hippocampus. In situ hybridization histochemistry is a frequently used technique in the Zigman lab.

In healthy individuals, ghrelin levels rise in the setting of negative energy balance, resulting in a potent stimulation of feeding. Administration of ghrelin stimulates eating, a decrease in energy expenditure and a resulting increase in body weight and adiposity. Exposure of ghrelin cells to low glucose also leads to ghrelin release, and in turn a series of ghrelin-initiated changes that help reverse the low glucose state.

Previous work by our group has shown that ghrelin also influences food reward and mood. Indeed, ghrelin levels rise in the setting of psychosocial stress, and evidence by our group and others suggests that ghrelin may help to minimize stress-induced depression while also inducing stress-based comfort food eating.

Study of the mechanisms of ghrelin action and release will help us eventually learn more about and find treatments for obesity, eating disorders such as anorexia nervosa, diabetes, depression and addiction.