ABSTRACT
@#Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.
ABSTRACT
BACKGROUND: It has been reported that the abdominal obesity can cause various metabolic abnormalities not only in adults but also in adolescents. This study was conducted to investigate lifestyle habits related to abdominal obesity in Korean adolescents. METHODS: This study is a cross-sectional study on 561 adolescents (305 boys and 256 girls) aged 12-18 years from the Korean National Health and Nutrition Examination Survey 2005. The abdominal obesity was defined as waist circumference at or above the 90th percentile for each age and gender based on the 2007 growth chart for Korean children. The frequency of physical activity, screen time, and the intake amount of energy and macronutrients were investigated as lifestyle habits. RESULTS: The prevalence of abdominal obesity in Korean adolescents aged 12-18 years was 9.1% (Boys, 9.4%; Girls, 8.7%). The mean of daily screen time was 4.3 +/- 0.1 hours (Boys, 4.4 +/- 0.2 hours; Girls, 4.2 +/- 0.2 hours). The subjects with daily screen time > or = 5 hours had a 3.0 times increased risk of abdominal obesity compared to subjects with daily screen time or = 35% of energy was 2.57 (95% confidence interval, 1.16 to 5.68; P-value = 0.020) with fat intake < 25% of energy as reference. The relationship between long screen time and abdominal obesity was observed in girls and high fat intake was related to abdominal obesity in boys. CONCLUSION: This study shows that abdominal obesity in Korean adolescents is associated to long screen time and high fat intake.