Role of X-Box Binding Protein-1 in Fructose-Induced Lipogenesis in HepG2 Cells / 中华医学杂志(英文版)

<p><b>Background</b>A high consumption of fructose leads to hepatic steatosis. About 20-30% of triglycerides are synthesized via de novo lipogenesis. Some studies showed that endoplasmic reticulum stress (ERS) is involved in this process, while others showed that a lipotoxic environment directly influences ER homeostasis. Here, our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 (XBP-1), one marker of ERS, on hepatic lipid accumulation stimulated by high fructose.</p><p><b>Methods</b>HepG2 cells were incubated with different concentrations of fructose. Upstream regulators of de novo lipogenesis (i.e., carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1c [SREBP-1c]) were measured by polymerase chain reaction and key lipogenic enzymes (acetyl-CoA carboxylase [ACC], fatty acid synthase [FAS], and stearoyl-CoA desaturase-1 [SCD-1]) by Western blotting. The same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid (TUDCA) or the ERS inducer thapsigargin. Finally, the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell transfection.</p><p><b>Results</b>Exposure to high fructose increased triglyceride levels in a dose- and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels of FAS, ACC, and SCD-1, concomitant with XBP-1 conversion to an active spliced form. Lipogenesis-associated factors induced by high fructose were inhibited by TUDCA and induced by thapsigargin. Triglyceride level in XBP-1-deficient group decreased significantly compared with high-fructose group (4.41 ± 0.54 μmol/g vs. 6.52 ± 0.38 μmol/g, P < 0.001), as mRNA expressions of SREBP-1c (2.92 ± 0.46 vs. 5.08 ± 0.41, P < 0.01) and protein levels of FAS (0.53 ± 0.06 vs. 0.85 ± 0.05, P = 0.01), SCD-1 (0.65 ± 0.06 vs. 0.90 ± 0.04, P = 0.04), and ACC (0.38 ± 0.03 vs. 0.95 ± 0.06, P < 0.01) decreased. Conversely, levels of triglyceride (4.22 ± 0.54 μmol/g vs. 2.41 ± 0.35 μmol/g, P < 0.001), mRNA expression of SREBP-1c (2.70 ± 0.33 vs. 1.00 ± 0.00, P < 0.01), and protein expression of SCD-1 (0.93 ± 0.06 vs. 0.26 ± 0.05, P < 0.01), ACC (0.98 ± 0.09 vs. 0.43 ± 0.03, P < 0.01), and FAS (0.90 ± 0.33 vs. 0.71 ± 0.02, P = 0.04) in XBP-1s-upregulated group increased compared with the untransfected group.</p><p><b>Conclusions</b>ERS is associated with de novo lipogenesis, and XBP-1 partially mediates high-fructose-induced lipid accumulation in HepG2 cells through augmentation of de novo lipogenesis.</p>

Real-time plantar pressure measurement for monitoring exercise load in daily life activities / 医用生物力学

Objective To monitor the exercise load in daily life activities, a reliable method to estimate the real-time plantar pressure based only on a few sensors was presented. Methods Pedar-X pressure insoles were applied to collect plantar pressures from 10 healthy young adults performing 5 typical motions (vertical jump-landing, level walking, level running, stair ascending and stair descending). Stepwise linear regression was performed to reconstruct a mathematic model of calculating the foot force for each style of the motion based on 99 individual pressure data. Then these models were validated by comparing the plantar pressures measured by Pedar-X system and the estimated values by these models when other 4 subjects conducted the same 5 motions and the continuous motion composed of the 5 motions. Results Regardless of the single motion or continuous motion, the foot force calculated by each model for each motion, as well as that calculated by level walking model for each motion were almost the same as the data measured by Pedar-X system. In addition, there was no significant difference between the estimated values by each motion model and level walking model. Conclusions The foot force in daily life activities can be monitored effectively by level walking model with only 5 pressure sensors placed under T1, M2, M3, HM and HL region of the foot.