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. 2012 Nov 9;7(11):e48801. doi: 10.1371/journal.pone.0048801

Figure 5. Fructose stimulates fat accumulation in HepG2 cells by activating AMPD2 and blocking AMPK and fat oxidation.

Figure 5

A) Fructose reduces intracellular phosphate levels –a natural inhibitor of AMPD activity- in a dose-dependent manner. *p<0.05, **p<0.01. B) AMPD2 expression is not modified by fructose in human hepatocytes. As control, fructokinase (KHK) expression is significantly up-regulated. **p<0.01. C) Both fructose (1–5 mM) and fructose-1-phosphate (1–5 mM) -the product of fructokinase metabolism- significantly up-regulates the activity of AMPD2 in human hepatocytes. AMPD activity was measured after 30 minutes exposure to fructose in 50 µg protein lysates *p<0.05, **p<0.01. D) Fructose stimulates AMPK activity (as determined by phosphorylation at Thr172) that is further amplified in AMPD2 silenced cells. *p<0.05, **p<0.01. E) Fructose induces triglyceride accumulation in HepG2 cells that is blocked in AMPD2 deficient cells *p<0.05, **p<0.01 F) Fructose decreases β- hydroxybutyrate levels in HepG2 cells that are blocked in AMPD2 deficient cells *p<0.05, **p<0.01. G) ECH1 expression is up-regulated in AMPD2 deficient cells exposed to fructose. H) Silencing AMPK expression increases triglyceride accumulation in non-exposed and fructose exposed HepG2 cells that is not blocked with 10 µM metformin *p<0.05, **p<0.01 I) Silencing AMPK expression decreases intracellular β- hydroxybutyrate levels in non-exposed and fructose exposed HepG2 cells that is not blocked with 10 µM metformin *p<0.05, **p<0.01, ***p<0.001.