Abstract：
:Central leptin action requires PI3K activity to modulate glucose homeostasis and peripheral metabolism. However, the mechanism behind this phenomenon is not clearly understood. We hypothesize that hypothalamic PI3K activity is important for the modulation of the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway, PGC1 alpha, and AKT in skeletal muscle (SM). To address this issue, we injected leptin into the lateral ventricle of rats. Hypothalamic JAK2 and AKT were activated by intracerebroventricular (ICV) injection of leptin in a time-dependent manner. Central leptin improved tolerance to glucose (GTT), increased PGC1 alpha expression, and AKT, AMPK, ACC and JAK2 phosphorylation in the soleus muscle. Previous ICV administration of either LY294002 or propranolol (IP) blocked these effects. We concluded that the activation of the hypothalamic PI3K pathway is important for leptin-induced AKT phosphorylation, as well as for active catabolic pathway through AMPK and PGC1 alpha in SM. Thus, a defective leptin signalling PI3K pathway in the hypothalamus may contribute to peripheral resistance to insulin associated to diet-induced obesity.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Roman EA,Reis D,Romanatto T,Maimoni D,Ferreira EA,Santos GA,Torsoni AS,Velloso LA,Torsoni MAdoi
10.1016/j.mce.2009.08.007subject
Has Abstractpub_date
2010-01-15 00:00:00pages
62-9issue
1eissn
0303-7207issn
1872-8057pii
S0303-7207(09)00411-0journal_volume
314pub_type
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