Ablation of Akt2 and AMPKα2 rescues high fat diet-induced obesity and hepatic steatosis through Parkin-mediated mitophagy

• DOI: 10.1016/j.apsb.2021.07.006
• Publication Date: 2021-07-14T09:03:50Z
• Authors: Shuyi Wang; Jun Tao; Huaguo Chen; Machender R. Kandadi; Mingming Sun; Haixia Xu; Gary D. Lopaschuk; Yan Lu; Junmeng Zheng; Hu Peng; Jun Ren
• Keywords: Steatosis

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined deletion Akt2 AMPKα2 fat diet-induced hepatic steatosis. Akt2-Ampkα2 double knockout (DKO) mice were placed high diet for 5 months. Glucose metabolism, energy cardiac function, lipid accumulation, steatosis examined. DKO lean without anthropometric defects. High intake led to adiposity decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which ablated but not Akt2-/- Ampkα2-/- mice. increased blood triglycerides cholesterol, promoted injury WT These eliminated Fat enlarged adipocyte size, effect was negated elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding (CHREBP), sterol regulatory 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), diglyceride O-acyltransferase (DGAT1), absent dampened mitophagy, inflammation phosphorylation forkhead box O1 (FoxO1) AMPKα1 (Ser485), eradicated by DKO. Deletion Parkin effectively nullified DKO-induced benefits against intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well enhanced Akt, AMPK FoxO1, consolidated RNA sequencing (RNAseq) mass spectrometry analyses rodent human livers. data suggest that concurrent offers resilience obesity steatosis, possibly through preservation Parkin-mediated mitophagy metabolism.