The Zigman Lab is composed of Dr. Zigman, our lab manager and senior research scientist, Sherri Osborne-Lawrence, and a core group of talented postdoctoral fellows/students/research associates/technicians. Our work spans the fields of molecular endocrinology, behavioral neuroscience, and neuroanatomy and includes mouse, human and cell culture experiments. Our tools include a one-of-a-kind collection of Zigman lab-generated novel mouse models, novel mouse behavioral models, and novel cell culture models with which to probe ghrelin action, ghrelin secretion and a coordinated gastric enteroendocrine cellular response to conditions relevant to perturbed metabolic states, stress and depression.

The Zigman Lab investigates the biological basis for complex eating and the neuro-hormonal framework linking eating behavior to affect, with the ultimate goal of designing new methods to prevent and treat extremes of body weight and associated disorders of affect and metabolism.  As mentioned, we mainly have used the ghrelin system as a muse, investigating how this peptide hormone and its receptor influence 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 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 much remains to be learned 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.