Xiang Zhong

Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases. Whether N6-methyladenosine (m6A) mRNA methylation impacts circadian regulation of lipid metabolism is unclear. Here, we show m6A mRNA methylation oscillations in murine liver depend upon a functional circadian clock. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of PPaRα. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaRα m6A abundance and increases PPaRα mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. Mechanistically, YTHDF2 binds to PPaRα to mediate its mRNA stability to regulate lipid metabolism. Induction of reactive oxygen species both in vitro and in vivo increases PPaRα transcript m6A levels, revealing a possible mechanism for circadian disruption on m6A mRNA methylation. These data show that m6A RNA methylation is important for circadian regulation of downstream genes and lipid metabolism, impacting metabolic outcomes.

The objective of this study was to determine the appropriate concentration of dietary supplementation of curcumin, and its effect on growth performance, intestinal morphology, fat metabolism and nutrients utilization of broiler chicks. Four hundred eighty, 1-day-old Arbor Acre broiler chicks were allocated into four groups with 6 replicates of 20 birds per cage. Birds were fed a corn-soybean basal diet supplemented with curcumin at 0 (control, CRM0), 100 (CRM100), 150 (CRM150) and 200 mg/kg (CRM200) levels for 42 days. All birds were kept in wire floor triple deck battery cages under semi-intensive housing management. The results revealed that dietary supplementation of curcumin at 200 mg/kg significantly improved live body weight and feed efficiency at marketing age (42 d); while, there was no significant difference on feed intake as compared to control. Curcumin significantly improved utilization of apparent metabolizable energy and decreased abdominal fat at 42 d in CRM150 and CRM200 broilers, respectively. Plasma T4 hormone level and fat utilization were significantly increased; while plasma cholesterol level was significantly reduced in dose dependent manner for CRM200 broilers. The results showed that dietary supplementation of curcumin influenced the histomorphological measurements of small intestinal villi. The villus height was significantly increased in duodenum, jejunum and ileum in curcumin supplemented broilers. Villus width was also significantly increased in duodenum and jejunum (42 d). While, there was no significant difference in ileum villus width. Furthermore, villus height to crypt depth ratio was significantly increased in all segments (except jejunum 42 d) of small intestine in CRM200 group; however, the intestinal crypt depth was lowered in curcumin supplemented broilers. In conclusion, supplementation of curcumin at 200 mg/kg feed enhanced the growth performance and fat metabolism, and increased villus absorptive area of small intestine, resulting in improved nutrients absorption in CRM200 group.

Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg. Results indicated that added 50 and 500 mg/kg nano-ZnOs showed minimal toxicity. However, 5000 mg/kg nano-ZnOs significantly decreased body weight (from week 4 to 16) and increased the relative weights of the pancreas, brain and lung. Added 5000 mg/kg nano-ZnOs significantly increased the serum glutamic-pyruvic transaminase activity and zinc content, and significantly enhanced mRNA expression of zinc metabolism-related genes, including metallothionein 1(32.66 folds), metallothionein 2 (31.42 folds), ZIP8 (2.21folds), ZIP14 (2.45 folds), ZnT1 (4.76 folds), ZnT2 (6.19 folds) and ZnT4 (1.82 folds). The biodistribution determination showed that there was a significant accumulation of zinc in the liver, pancreas, kidney, and bones (tibia and fibula) after receiving 5000 mg/kg nano-ZnO diet, while no significant effects on Cu, Fe, and Mn levels, except for liver Fe content and pancreas Mn level. Our results demonstrated that long term exposure to 50 and 500 mg/kg nano-ZnO diets showed minimal toxicity. However, high dose of nano-ZnOs (5000 mg/kg) caused toxicity on development, and altered the zinc metabolism and biodistribution in mice.

Abstract N 6 ‐methyladenosine (m 6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m 6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)‐induced liver injury and lipid metabolism disorder, and on m 6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups ( n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets ( p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection ( p < 0.05). Additionally, curcumin reduced the expression of Bcl‐2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver ( p < 0.05). Curcumin inhibited the enhancement of SREBP‐1c and SCD‐1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3 , METTL14 , ALKBH5 , FTO , and YTHDF2 mRNA, and increased the abundance of m 6 A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS‐induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m 6 A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases.