Omics Insights into Metabolic Stress and Resilience of Rats in Response to Short-term Fructose Overfeeding.

SCOPE: Considerable evidence supports the view that high-fructose intake is associated with increased and early incidence of obesity and dyslipidemia. However, knowledge on physiopathological alterations introduced by fructose overconsumption is lacking. Therefore, an integrated omics analysis is carried out to investigate the consequences of short-term fructose overfeeding (SFO) and identify the underlying molecular mechanisms. METHODS AND RESULTS: SFO of rats demonstrates obvious histopathological hepatic lipid accumulation and significant elevation in adiposity, total cholesterol, and fasting plasma glucose levels. Integrated omics analysis demonstrates that SFO disturbed metabolic homeostasis and initiated metabolic stress. Hepatic lipogenesis pathways are also negatively impacted by SFO. Analysis of molecular networks generated by ingenuity pathway analysis (IPA) implicates involvement of the extracellular signal regulated kinase (ERK) signaling pathway in SFO and its consequences. Moreover, it is identified that an inherent negative feedback regulation of hepatic sterol regulatory element binding protein 1 (SREBP1) plays an active role in regulating hepatic de novo lipogenesis. CONCLUSION: The findings indicate that SFO disturbs metabolic homeostasis and that endogenous small molecules positively mediate SFO-induced metabolic adaption. The results also underline that an inherent regulatory mechanism of resilience occurs in response to fructose overconsumption, suggesting that efforts to maintain resilience can be a promising target to prevent and treat metabolic disorder-like conditions.

Evaluation of body surface area formulae for scaling GFR of adult renal patients: more between-subject variability explained by the DuBois & DuBois formula.

BACKGROUND: Scaling glomerular filtration rate (GFR) to body surface area (BSA) has been widely accepted, and was debated in recent years. Although the indexation ability of BSA is inferior to other physiological variables, the evaluation of BSA formulae is still meaningful to clinical practice. In this study, to evaluate the indexation ability of BSA formulae, the repeated measures analyses of camera-based scintigraphy (Gates method, gGFR) and plasma-based clearance (pGFR) were used to specially focus on the between-subject variability that tried to be minimized by GFR normalization. METHODS: The patients, who were older than 18 y and suffered from renal diseases, were enrolled and grouped according to the Chinese BMI (body mass index) criteria. All patients accepted renal scintigraphy and plasma clearance examinations. The gGFR and pGFR were separately scaled to DuBois & DuBois, Boyd, Stevenson, Gehan, Haycock, Mosteller, Hu and Livingston and Lee's formula. In the repeated measures analyses, the intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC) and the ratio of residual standard deviation to pooled standard deviation (RSD/PSD) were used for the evaluation. RESULTS: During January 2010 and May 2012, 220 patients were enrolled. The evaluated BSA formulae had well correlated results and significant differences among BMI groups. From high to low, the sequence of the correlation between BMI and BSA formula was L-L, Haycock, Gehan, Boyd, Mosteller, Stevenson, Hu and DuBois & DuBois formula. Both the scaled indices (ICC and CCC) and RSD/PSD indicated that, the sequence of indexation ability of BSA equations was Livingston < Haycock < Gehan < Stevenson < Mosteller < Boyd < Hu < DuBois & DuBois. CONCLUSIONS: Among the evaluated BSA formulae, DuBois & DuBois formula correlates to BMI the worst, and has the best indexation ability in scaling GFR of adult renal patients.

Lean body mass is better than body surface area in correcting GFR.

PURPOSE: The Gates-based renography (gGFR) and plasma-based clearance rate (pGFR) are conventionally corrected with body surface area (BSA). Limited studies indicated that the lean body mass (LBM) might be better than BSA in correcting pGFR. Therefore, we suggest that LBM is also better in correcting gGFR and improve the correlation coefficient between gGFR and pGFR. METHOD: During June 2009 and December 2010, the gGFR and pGFR of 63 patients with hydronephrosis were measured and corrected with BSA and LBM, respectively. The correlation and regression analyses were conducted to illustrate the power of BSA and LBM correction. RESULTS: In a paired t test, there was no significant difference between pGFR and gGFR in patients with stages 1 and 2, although this was significant in stages 3 and 4. However, neither LBM nor BSA correction could eliminate the difference. In all patients (N = 63), the correlation coefficient (r) between pGFR and gGFR was 0.794 (P <; 0.001). After the BSA and LBM correction, r was improved to 0.809 and 0.828, respectively. In all patients, the regression line of pGFR(LBM) - gGFR(LBM) was nearer to the original point and its slope closer to 1 than pGFR(BSA) - gGFR(BSA) and pGFR - gGFR. Similar results were found in the analysis of most stages and subgroups. CONCLUSIONS: The commonsense of BSA correction should be seriously reevaluated. Lean body mass can better improve the correlation coefficient between paired GFRs than BSA can and it can be suitable in the correction.

Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly. The exact pathogenic mechanisms of POCD are still unknown. In this study, we investigated the role of iron accumulation within the central nervous system in the development of cognitive dysfunction in rats following splenectomy. Cognitive function was assessed using a Morris water maze on postoperative days 1, 3, and 7. Impaired cognitive function was observed on days 1 and 3 after splenectomy, while an anesthesia-alone group showed no significant difference from the control. Serum iron levels decreased and brain iron content increased on days 1 and 3 after surgery, which was in parallel with the impairment of cognitive function. Furthermore, the levels of proteins involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals when compared with those of the control. The alterations in iron homeostasis were accompanied by intensified oxidative stress as measured by increases in the lipid peroxidation product, malondialdehyde, and a decrease in the levels of superoxide dismutase activity. Overall, these findings suggest that the impaired cognitive function was primarily due to surgical trauma rather than anesthesia. Increased iron accumulation and oxidative stress in the brain, especially in the hippocampus, may be involved in the pathogenesis of POCD.

[Radioiodine-131 therapy improves sex hormones and sexual function in male patients with Graves' disease].

OBJECTIVE: To observe the changes of sex hormones and sexual function in male patients with Graves' disease (GD) after Radioiodine-131 (I-131) therapy. METHODS: Thirty-four male GD patients, aged 21 -40 (32.3 +/- 6.7) years, were treated with I-131 at the dose of 111 - 407 (237.8 +/- 51.8) MBq. The levels of serum sex hormones were measured, and the patients'scores on erectile function (IIEF-5) were obtained before and 3 and 6 months after the treatment. Another 20 healthy men aged 25 - 37 (31 +/- 3.1) years were enlisted as controls. RESULTS: The baseline levels of estrogen (E2), testosterone (T) and luteinizing hormone (LH) were (132.5 +/- 40.4) pmol/L, (21.6 +/- 4.6) nmol/L and (10.1 +/- 4.4) IU/L in the GD patients, significantly higher than (80.4 +/- 31.2) pmol/L, (14.5 +/- 4.2) nmol/L and (6.2 +/- 1.9) IU/L in the healthy controls (P < 0.05). The E2, T and LH levels showed a significant decrease in the GD patients after 3 months of treatment ([110.2 +/- 20.6] pmol/L, [17.7 +/- 5.5] nmol/L and (9.4 +/- 3.9) IU/L, P < 0.05), but exhibited no statistically significant differences from the healthy controls at 6 months ([82.6 +/- 30.1] pmol/L, [13.8 +/- 3.4 ] nmol/L and [6.6 +/- 1.5] IU/L, P > 0.05). The IIEF-5 score of the GD patients was 5 - 25 (15.5 +/- 3.5) before I-131 treatment, significantly lower than that of the controls (19 - 25, 24 +/- 0.5) (P < 0.05), and it was 8 - 25 (19.5 +/- 1.0) at 3 months and 10 - 25 (23.5 +/- 1.5) at 6 months, significantly higher in the latter than in the former (P < 0.05), and with no significant difference between the 6-month treated patients and the healthy controls (P > 0.05). CONCLUSION: The E2, T and LH levels are increased while the IIEF-5 score decreased markedly in male GD patients. Six-month treatment with I-131 can not only restore the E2, T and LH levels to normal but also significantly improve the patient's sexual function.