Zinc‐Induced Hyperleptinemia Relates to the Amelioration of Sucrose‐Induced Obesity with Zinc Repletion

Objective: Dietary zinc repletion can ameliorate sucrose‐induced obesity. A positive correlation between zinc and leptin has been recently noted, and both are known as important mediators in appetite control. In this study, we examined whether the reported amelioration of sucrose‐induced obesity by zinc repletion was consequent on the changes in circulating leptin levels. Research Methods and Procedures: Mice with obesity that was induced by giving a 32% sucrose solution in addition to a semipurified diet were divided into two groups based on whether they had 20 mg/liter zinc supplementation in their drinking water. Results: As expected, the mice with sucrose‐induced obesity had hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hypozincemia when compared with the mice given the diet alone. Body weight gain, body fat content, and food and sucrose intake tended to decrease but not with statistical significance in sucrose‐fed obese mice with zinc supplementation. Nevertheless, some serum variables (glucose, insulin, triglycerides, and zinc) in sucrose‐fed obese mice with zinc treatment were approximate to those values of the mice given the diet alone. Moreover, sucrose‐fed obese mice with zinc supplementation had the highest serum values of leptin. Discussion: This study indicates that the amelioration of sucrose‐induced obesity by zinc repletion may be partly attributable to the hyperleptinemia induced by the mineral.     

Diet‐Induced Changes in Stearoyl‐CoA Desaturase 1 Expression in Obesity‐Prone and ‐Resistant Mice

Objective: To investigate stearoyl‐coenzyme A desaturase (SCD) 1 expression in obesity‐prone C57BL/6 mice and in obesity‐resistant FVB mice to explore the relationship of SCD1 expression and susceptibility to diet‐induced obesity. Research Methods and Procedures: Nine‐week‐old C57BL/6 and FVB mice were fed either a high‐ or low‐fat diet for 8 weeks. Body weight and body composition were measured before and at weeks 4 and 8 of the study. Energy expenditure was measured at weeks 1 and 5 of the study. Hepatic SCD1 mRNA was measured at 72 hours and at the end of study. Plasma leptin and insulin concentrations were measured at the end of study. Results: When C57BL/6 mice were switched to a calorie‐dense high‐fat diet, animals gained significantly more body weight than those maintained on a low‐calorie density diet primarily due to increased fat mass accretion. Fat mass continued to accrue throughout 8 weeks of study. Increased calorie intake did not account for all weight gain. On the high‐fat diet, C57BL/6 mice decreased their energy expenditure when compared with mice fed a low‐fat diet. In response to 8 weeks of a high‐fat diet, SCD1 gene expression in liver increased >2‐fold. In contrast, feeding a high‐fat diet did not change body weight, energy expenditure, or SCD1 expression in FVB mice. Discussion: Our study showed that a high‐fat hypercaloric diet increased body adiposity first by producing hyperphagia and then by decreasing energy expenditure of mice susceptible to diet‐induced obesity. Consumption of a high‐fat diet in species predisposed to obesity selectively increased SCD1 gene expression in liver.     

Prophylactic and Therapeutic Potential of Acetyl‐l‐carnitine against Acetaminophen‐Induced Hepatotoxicity in Mice

Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen‐induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N‐acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N‐acetylcystiene in the treatment of acetaminophen toxicity.     

Disorder‐Induced Open‐Circuit Voltage Losses in Organic Solar Cells During Photoinduced Burn‐In

The photoinduced open‐circuit voltage (V_oc) loss commonly observed in bulk heterojunction organic solar cells made from amorphous polymers is investigated. It is observed that the total charge carrier density and, importantly, the recombination dynamics are unchanged by photoinduced burn‐in. Charge extraction is used to monitor changes in the density of states (DOS) during degradation of the solar cells, and a broadening over time is observed. It is proposed that the V_oc losses observed during burn‐in are caused by a redistribution of charge carriers in a broader DOS. The temperature and light intensity dependence of the V_oc losses can be described with an analytical model that contains the amount of disorder broadening in a Gaussian DOS as the only fit parameter. Finally, the V_oc loss in solar cells made from amorphous and crystalline polymers is compared and an increased stability observed in crystalline polymer solar cells is investigated. It is found that solar cells made from crystalline materials have a considerably higher charge carrier density than those with amorphous materials. The effects of a DOS broadening upon aging are suppressed in solar cells with crystalline materials due to their higher carrier density, making crystalline materials more stable against V_oc losses during burn‐in.     

Curcumin Ameliorates Streptozotocin‐Induced Heart Injury in Rats

Heart failure (HF) is one of diabetic complications. This work was designed to investigate the possible modulatory effect of curcumin against streptozotocin‐induced diabetes and consequently HF in rats. Rats were divided into control, vehicle‐treated, curcumin‐treated, diabetic‐untreated, diabetic curcumin–treated, and diabetic glibenclamide–treated groups. Animal treatment was started 5 days after induction of diabetes and extended for 6 weeks. Diabetic rats showed significant increase in serum glucose, triglycerides, total cholesterol, low‐density lipoprotein‐cholesterol, very low density lipoprotein‐cholesterol, nitric oxide, lactate dehydrogenase, cardiac malondialdehyde, plasma levels of interleukin‐6, and tumor necrosis factor‐alpha, and also showed marked decrease in serum high‐density lipoprotein‐cholesterol, cardiac reduced glutathione, and cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione‐S‐transferase). However, curcumin or glibenclamide treatment significantly mitigated such changes. In conclusion, curcumin has a beneficial therapeutic effect in diabetes‐induced HF, an effect that might be attributable to its antioxidant and suppressive activity on cytokines.     

Nrf2‐Mediated Resistance to Oxidant‐Induced Redox Disruption in Embryos

Events that control developmental changes occur during specific windows of gestation and if disrupted, can lead to dysmorphogenesis or embryolethality. One largely understudied aspect of developmental control is redox regulation, where the untimely disruption of intracellular redox potentials (E_h) may alter development, suggesting that tight control of developmental‐stage–specific redox states is necessary to support normal development. In this study, mouse gestational day 8.5 embryos in whole embryo culture were treated with 10 μM dithiole‐3‐thione (D3T), an inducer of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2). After 14 hr, D3T‐treated and ‐untreated conceptuses were challenged with 200 μM hydrogen peroxide (H₂O₂) to induce oxidant‐induced change to intracellular E_hs. Redox potentials of glutathione (GSH), thioredoxin‐1 (Trx1), and mitochondrial thioredoxin‐2 (Trx2) were then measured over a 2‐hr rebounding period following H₂O₂ treatment. D3T treatment increased embryonic expression of known Nrf2‐regulated genes, including those responsible for redox regulation of major intracellular redox couples. Exposure to H₂O₂ without prior D3T treatment produced significant oxidation of GSH, Trx1, and Trx2, based on E_h values, where GSH and Trx2 E_h recovered, reaching to pre‐H₂O₂ E_h ranges, but Trx1 E_h remained oxidized. Following H₂O₂ addition in culture to embryos that received D3T pretreatments, GSH, Trx1, and Trx2 were insulated from significant oxidation. These data show that Nrf2 activation may serve as a means to protect the embryo from chemically induced oxidative stress through the preservation of intracellular redox states during development, allowing normal morphogenesis to ensue.     

Cold‐Induced Adaptive Thermogenesis in Lean and Obese

On entering a cold environment, people react by increasing insulation and energy expenditure (EE). However, large interindividual differences exist in the relative contribution of each mechanism. Short‐term studies revealed that obese subjects increase EE (i.e., adaptive thermogenesis) less than lean subjects, which might have implications for the predisposition to obesity. In this study, we validate the differences in adaptive thermogenesis between lean and obese upon midterm mild cold exposure. Therefore, 10 lean and 10 obese subjects were exposed for 48 h to mild cold (16 °C) in a respiration chamber. The preceding 36 h they stayed in the same chamber at a neutral temperature (22 °C) for the baseline measurements. EE, physical activity, skin temperature, and core temperature have been measured for the last 24 h of both parts. Mean daytime EE increased significantly in the lean subjects (P < 0.01), but not in the obese. Physical activity decreased significantly in the lean (P < 0.01) and the obese (P < 0.001) subjects. The change in EE was related to the change in physical activity in both groups (respectively R² = 0.673, P < 0.01 and R² = 0.454, P < 0.05). Upon mild cold exposure, lean subjects decreased proximal skin temperature less, but distal skin temperature more than obese. In conclusion, the interindividual differences in cold‐induced thermogenesis were related to changes in physical activity in both lean and obese, pointing at the existence of individual variation in physical activity to compensate for cold‐induced thermogenesis. Furthermore, although a large part of the lean subjects counteracted the cold by increasing EE, most obese subjects changed temperature distribution, and therefore, increased insulation.