English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Insulin and leptin intracellular signaling pathways converge and act synergistically on the hypothalamic phosphatidylinositol-3-OH kinase/3-phosphoinositide-dependent protein kinase 1 (PDK1). However, little is known about whether PDK1 in agouti-related peptide (AGRP) neurons contributes to energy homeostasis. We generated AGRP neuron-specific PDK1 knockout ( AGRPPdk1 −/−  ) mice and mice with selective expression of transactivation-defective Foxo1 ( Δ256Foxo1 AGRP Pdk1 −/−  ). The  AGRPPdk1 −/−   mice showed reductions in food intake, body length, and body weight. The  Δ256Foxo1 AGRP Pdk1 −/−   mice showed increased body weight, food intake, and reduced locomotor activity. After four weeks of calorie-restricted feeding, oxygen consumption and locomotor activity were elevated in  AGRPPdk1 −/−   mice and reduced in  Δ256Foxo1 AGRP Pdk1 −/−   mice.  In vitro , ghrelin-induced changes in [Ca 2+ ] i  and inhibition of ghrelin by leptin were significantly attenuated in  AGRPPdk1 −/−   neurons compared to control neurons. However, ghrelin-induced [Ca 2+ ] i  changes and leptin inhibition were restored in  Δ256Foxo1 AGRP Pdk1 −/−   mice. These results suggested that PDK1 and Foxo1 signaling pathways play important roles in the control of energy homeostasis through AGRP-independent mechanisms.

PDK1-Foxo1 in Agouti-Related Peptide Neurons Regulates Energy Homeostasis by Modulating Food Intake and Energy Expenditure