Details

Autor(en) / Beteiligte

• Perry, Rachel J.
• Wang, Yongliang
• Cline, Gary W.
• Rabin-Court, Aviva
• Song, Joongyu D.
• Dufour, Sylvie
• Zhang, Xian Man
• Petersen, Kitt Falk
• Shulman, Gerald I.

Titel

Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation

Ist Teil von

• Cell, 2018-01, Vol.172 (1-2), p.234-248.e17

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The transition from the fed to the fasted state necessitates a shift from carbohydrate to fat metabolism that is thought to be mostly orchestrated by reductions in plasma insulin concentrations. Here, we show in awake rats that insulinopenia per se does not cause this transition but that both hypoleptinemia and insulinopenia are necessary. Furthermore, we show that hypoleptinemia mediates a glucose-fatty acid cycle through activation of the hypothalamic-pituitary-adrenal axis, resulting in increased white adipose tissue (WAT) lipolysis rates and increased hepatic acetyl-coenzyme A (CoA) content, which are essential to maintain gluconeogenesis during starvation. We also show that in prolonged starvation, substrate limitation due to reduced rates of glucose-alanine cycling lowers rates of hepatic mitochondrial anaplerosis, oxidation, and gluconeogenesis. Taken together, these data identify a leptin-mediated glucose-fatty acid cycle that integrates responses of the muscle, WAT, and liver to promote a shift from carbohydrate to fat oxidation and maintain glucose homeostasis during starvation. [Display omitted] •Hypoleptinemia promotes HPA-axis-driven WAT lipolysis to maintain euglycemia•Increased hepatic acetyl-CoA content maintains euglycemia during starvation•Substrate limitation reduces mitochondrial VCS and VPC flux during a prolonged fast An integrated response driven by leptin levels plays an important role during starvation to promote the shift from carbohydrate to fat metabolism and in maintenance of gluconeogenesis