March 13, 2012

The Scientist: Prof. Ling Qi Examines Fat Cell Responses to Obesity and Diabetes

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Obesity and diabetes share an undeniable connection, but what exactly is it? Prof. Ling Qi, nutritional sciences, and his team of researchers are trying to find out. His team is currently focusing on trying to understand the pathogenesis of obesity and diabetes, Qi said. “The long term goal is to delineate a molecular mechanism that leads to the obesity associated type II diabetes,” he added.

Lipids play an underlying role in the outcome of obesity related diabetes. When people eat a Western diet rich in lipids, these lipids induce cellular changes in cells that eventually confer insulin-resistance in those cells. More specifically, Qi’s research explores the response of these fat cells to stress. His work focuses on the endoplasmic reticulum, a protein factory in the cell that makes, folds and transports proteins.

“When there are accumulations of misfolded proteins in the ER, they tend to cause a stress response. We call this an ER stress response,” Qi said. A buildup of stress in the ER affects its ability to secrete proteins in fat cells that affect eating behaviors and metabolism. Thus, a reduced efficiency in their secretion changes the insulin sensitivity of cells throughout the entire body, according to Qi.

To counteract this stress, “These proteins initiate a signaling cascade to the ER to the nucleus and the nucleus responds by upregulating ER chaperones,” Qi said. Chaperons in the ER help with protein folding and protein lipidation, which consequently reduce stress and improve systemic insulin sensitivity.

In a paper he previously published in the June 2009 issue of Cell Metabolism, Qi described his discovery of an ER stress response pathway involved with the development of fat cells. He and his team found that when faced with stress, fat cells lacking in IRE1alpha, a chaperon protein that senses misfolded proteins and initiates the unfolded protein response to restore proper protein folding, were unable to transition from pre-adipocytes, or pre-fat cells, to mature fat cells. This interference in fat cell development sheds light on the mechanisms that produce obesity-causing fat cells.

Currently, Qi and his research team are investigating how the ER stress response affects not only regular obesity, but also obesity associated with type II diabetes. “Nowadays, we are further addressing the question of whether ER stress affects the progression of obesity into type II diabetes,” he said. Qi’s work involves the use of mouse models to study ER defective mice that lack a central component on the ER membrane that produces the stress response pathway.

“We are also specifically using conditional knockout mouse models and knockout genes in the macrophages, in the adipocytes, in other tissue cell types, and in the intestines as well, just to see how they affect systemic insulin sensitivity,” Qi said. Conditional knockout mouse models are genetically engineered mice that contain tissue-specific inactivations of genes producing ER stress responses.

One of Qi’s goals with his research is to translate his findings into therapeutic strategies for treatment for type II diabetes as well as other obesity-related health problems, he said.

“I get up every morning, and I get so excited about what we do. And sometimes I can’t sleep because really what we’re doing is actually opening up a new area that may have significant implications for our understanding of the development of obesity associated type II diabetes,” Qi said.

According to Qi, his enthusiasm for his research comes from his fascination with its application in everyday life. “By understanding how obesity develops it helps you to understand yourself,” he said. “That’s why I felt so interested and that’s what drives me—trying to understand myself better and how my tissues and how my organs work.”

In addition to his active research, Qi also teaches NS3310: Physiological and Biochemical Bases of Human Nutrition. The course explores the fundamentals of human nutritional requirements with an integrated approach that combines concepts from biochemistry, organic chemistry, and anatomy and physiology.

He said that what he enjoys most about teaching this class is that at the end of the semester, students tell him how his class has changed their diet and affected the way they make food choices. “This class is so helpful because it is so applicable to your daily life,” he said. After students learn more about how certain foods translate into energy and fats, he added, they become more health-conscious about what they consume.

While Qi shows great dedication to his research, he also finds teaching to be an equally rewarding experience.

“I feel that research and teaching in class really goes hand-in-hand,” Qi said. “For me, If I could be a better teacher, it really motivates me to learn more about the materials I’m teaching and it also motivates me to do better research,” he said. And through this research, he added, that he plans to make new discoveries that are “meaningful for everybody.”

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Original Author: Jennifer Chen

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