Details

Autor(en) / Beteiligte

• Shen, Ling
• Lo, Chunmin C.
• Woollett, Laura A.
• Liu, Min

Titel

Apolipoprotein A-IV exerts its anorectic action through a PI3K/Akt signaling pathway in the hypothalamus

Ist Teil von

• Biochemical and biophysical research communications, 2017-12, Vol.494 (1-2), p.152-157

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Apolipoprotein A-IV (apoA-IV) is a satiation factor that acts in the hypothalamus, however, the intracellular mechanisms responsible for this action are still largely unknown. Here we report that apoA-IV treatment elicited a rapid activation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in cultured primary hypothalamic neurons, and this effect was significantly attenuated by pretreatment with LY294002, an inhibitor of the PI3K pathway. To determine if the activation of PI3K is required for apoA-IV's inhibitory effect on food intake, apoA-IV was administered intracerebroventricularly. We found that apoA-IV significantly reduced food intake and activated PI3K signaling in the hypothalamus, and these effects were abolished by icv pre-treatment with LY294002. To identify the distinct brain sites where apoA-IV exerts its anorectic action, apoA-IV was administered into the ventromedial hypothalamus (VMH) through implanted bilateral cannula. At a low dose (0.5 μg), apoA-IV significantly inhibited food intake and activated PI3K signaling pathway in the VMH of lean rats, but not in high-fat diet-induced obese (DIO) rats. These results collectively demonstrate a critical role of the PI3K/Akt pathway in apoA-IV's anorectic action in lean rats and suggest a defective PI3K pathway in the VMH is responsible for the impaired apoA-IV's anorectic action in the DIO animals. •ApoA-IV increases the activation of PI3K/Akt signaling pathway in cultured primary hypothalamic neuronal cells.•Icv pretreatment of PI3K inhibitor significantly attenuates apoA-IV's action on food intake.•ApoA-IV administered into VMH inhibits food intake and activates PI3K/Akt pathway in lean, but not in DIO rats.