Hepatic IKKε expression is dispensable for high-fat feeding-induced increases in liver lipid content and alterations in glucose tolerance
© 2020 the American Physiological Society. There are endocrine and immunological changes that occur during onset and progression of the overweight and obese states. The inhibitor of nuclear factor-κB kinase-ε (IKKε) was originally described as an inducible protein kinase; whole body gene deletion or systemic pharmaceutical targeting of this kinase improved insulin sensitivity and glucose tolerance in mice. To investigate the primary sites of action associated with IKKε during weight gain, we describe the first mouse line with conditional elimination of IKKε in the liver (IKKεAlb-/-). IKKεAlb-/- mice and littermate controls gain weight, show similar changes in body composition, and do not display any improvements in insulin sensitivity or whole body glucose tolerance. These studies were conducted using breeder chow diets and matched low- vs. high-fat diets. While glycogen accumulation in the liver is reduced in IKKεAlb-/- mice, lipid storage in liver is similar in IKKεAlb-/- mice and littermate controls. Our results using IKKεAlb-/-mice suggest that the primary action of this kinase to impact insulin sensitivity during weight gain lies predominantly within extrahepatic tissues.
Publication Source (Journal or Book title)
American Journal of Physiology - Endocrinology and Metabolism
Jason Collier, J., Batdorf, H., Mendoza, T., Burk, D., Martin, T., Zhang, J., Mynatt, R., & Burke, S. (2020). Hepatic IKKε expression is dispensable for high-fat feeding-induced increases in liver lipid content and alterations in glucose tolerance. American Journal of Physiology - Endocrinology and Metabolism, 318 (1), E11-E21. https://doi.org/10.1152/ajpendo.00309.2019