Inflammatory Links between Obesity and Type 2 Diabets

Friday, November 4, 2016 -
2:00pm to 3:00pm
FUNG Auditorium, Powell-Focht Bioengineering Hall
Alan Saltiel, Ph.D.

Professor and Director

Department of Medicine

UC San Diego

 

 

Inflammatory Links between Obesity and Type 2 Diabets

Abstract: 
Obesity is associated with chronic low­grade inflammation that negatively impacts insulin sensitivity. This involves infiltration of M1 polarized proinflammatory macrophages into fat tissue, as well as inflammatory events in liver. High fat diet can increase NFkB activation in mice, which leads to a sustained elevation in level of IkB kinase e (IKKe) in liver, adipocytes and adipose tissue macrophages. IKKe knockout mice are protected from high fat diet­induced obesity, chronic inflammation in liver and fat, hepatic steatosis and whole­body insulin resistance.  These mice show increased energy expenditure and thermogenesis on high fat diet compared to wild type mice. They maintain insulin sensitivity in liver and fat, without activation of the proinflammatory JNK pathway associated with obesity. Gene expression analyses indicate that targeted deletion of IKKe increases expression of the uncoupling protein UCP­1, reduces expression of inflammatory cytokines, and changes expression of certain regulatory proteins and enzymes involved in glucose and lipid metabolism. Thus, IKKe may represent an attractive new therapeutic target for obesity, insulin resistance, diabetes and other complications associated with these disorders.  
Bio: 

Alan Saltiel received his AB in Zoology from Duke University in 1975 with Magna Cum Laude distinction, and his Ph.D. in Biochemistry from the University of North Carolina in 1980. From 1981­1984 he did postdoctoral training with Pedro Cuatrecasas at the Wellcome Research Laboratories in Research Triangle Park, NC, studying mechanisms of insulin action. In 1984 he moved to the Rockefeller University as Assistant Professor, continuing work on the molecular and cellular biology of the actions of insulin and growth factors. In 1990 he joined Parke Davis Pharmaceutical Research as Distinguished Research Fellow and Senior Director of Cell Biology at Parke Davis, and directed drug discovery activities in diabetes, obesity and cancer. He was responsible for preclinical studies on troglitazone, the first thiazolidinedione approved for the treatment of type 2 diabetes. He also developed the first MEK inhibitors for the treatment of cancer­the first received FDA approval for melanoma and other cancers.  In 2001, Dr. Saltiel moved to the newly created Life Sciences Institute of the University of Michigan and was named founding Director of the Institute, and John Jacob Abel Professor in the Life Sciences. The Institute is now home to 30 faculty and over 400 scientists in all areas of life sciences. In 2015 he moved to the University of California, San Diego to create the Institute for Diabetes and Metabolic Health; he directs the Institute and serves as Professor of Medicine and Pharmacology. He has received numerous awards, including the Rosalyn Yalow Research and Development Award from the American Diabetes Association, the Hirschl Award, the John Jacob Abel and the Goodman and Gilman Awards from ASPET, was elected as a fellow of the American Association for the Advancement of Science, and elected to membership in the American Society of Clinical Investigation and the Institute of Medicine of the National Academy of Sciences, now the National Academy of Medicine. He has given many named lectures and organized numerous meetings and conferences, and served on a number of advisory panels, scientific and editorial boards.  He has nineteen issued patents, and has published over 290 original papers.