Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism

K. Ganesh Kumar, James L. Trevaskis, Daniel D. Lam, Gregory M. Sutton, Robert A. Koza, Vladimir N. Chouljenko, Konstantin G. Kousoulas, Pamela M. Rogers, Robert A. Kesterson, Marie Thearle, Anthony W. Ferrante, Randall L. Mynatt, Thomas P. Burris, Jesse Z. Dong, Heather A. Halem, Michael D. Culler, Lora K. Heisler, Jacqueline M. Stephens, Andrew A. Butler*

*Corresponding author for this work

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

Obesity and nutrient homeostasis are linked by mechanisms that are not fully elucidated. Here we describe a secreted protein, adropin, encoded by a gene, Energy Homeostasis Associated (Enho), expressed in liver and brain. Liver Enho expression is regulated by nutrition: lean C57BL/6J mice fed high-fat diet (HFD) exhibited a rapid increase, while fasting reduced expression compared to controls. However, liver Enho expression declines with diet-induced obesity (DIO) associated with 3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state. In DIO mice, transgenic overexpression or systemic adropin treatment attenuated hepatosteatosis and insulin resistance independently of effects on adiposity or food intake. Adropin regulated expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma, a major regulator of lipogenesis. Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity.

Original languageEnglish
Pages (from-to)468-481
Number of pages14
JournalCell Metabolism
Volume8
Issue number6
Early online date2 Dec 2008
DOIs
Publication statusPublished - 6 Dec 2008

Keywords

  • adipose-tissue
  • insulin-resistance
  • melanocortin system
  • food-intake
  • receptor
  • glucose
  • obesity
  • liver
  • mice
  • pathogenesis

Cite this

Kumar, K. G., Trevaskis, J. L., Lam, D. D., Sutton, G. M., Koza, R. A., Chouljenko, V. N., Kousoulas, K. G., Rogers, P. M., Kesterson, R. A., Thearle, M., Ferrante, A. W., Mynatt, R. L., Burris, T. P., Dong, J. Z., Halem, H. A., Culler, M. D., Heisler, L. K., Stephens, J. M., & Butler, A. A. (2008). Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metabolism, 8(6), 468-481. https://doi.org/10.1016/j.cmet.2008.10.011