While the loss of endothelial FTO did not influence the development of obesity and dyslipidemia, it protected mice from high fat diet (HFD)- induced glucose intolerance and insulin resistance by increasing AKT phosphorylation in endothelial cells and skeletal muscle.
PI3K/AKT pathway damaged in various tissues of the body leads to obesity and type 2 diabetes as the result of insulin resistance, and in turn, insulin resistance exacerbates the PI3K/AKT pathway, forming a vicious circle.
Chronic intracellular Ca<sup>2+</sup> overload in hepatocytes during obesity and hyperlipidemia attenuates the phosphorylation of protein kinase B (Akt) and its key downstream signaling molecules by inhibiting membrane localization of pleckstrin homology (PH) domains.
Hypersecretion of IGF1 causes increased expression of lipogenic genes via activating the protein kinase B (PKB; also known as Akt)-mammalian target of rapamycin (mTOR) pathway in adipose tissues, which contributes to the development of obesity, diabetes, and hepatic steatosis as the KI mice age.
Our obese mouse models demonstrated activation of the AKT/mTOR pathway in obesity-accelerated mammary tumor growth (3.7- to 7.0-fold; P < .001; n = 6-7 mice per group).
Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1, MiR-103, and MiR-21 but increased Kitlg, Akt1, and miR-184 levels relative to lean littermates.
Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis, inflammation, insulin resistance, and obesity were also significantly reduced in NCKD relative to MCD tumors.
Adult heterozygous Pps mutant mice show increased insulin sensitivity and reduced diet-induced obesity with increased Akt/protein kinase B (PKB) phosphorylation in skeletal muscle but not in adipose tissue.