Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD.

Metformin prevents progression of non-alcoholic fatty liver disease (NAFLD). However, the potential mechanism is not entirely understood. Ferroptosis, a recently recognized nonapoptotic form of regulated cell death, has been reported to be involved in the pathogenesis of NAFLD. Here, we investigated the effects of metformin on ferroptosis and its potential mechanism in NAFLD. We found that metformin prevented the progression of NAFLD, and alleviated hepatic iron overload (HIO), ferroptosis and upregulated ferroportin (FPN) expression in vivo and in vitro. Mechanically, metformin reduced the lysosomal degradation pathway of FPN through activation AMPK, thus upregulated the expression of FPN protein, alleviated HIO and ferroptosis, and prevented progression of NAFLD. These findings discover a mechanism of metformin, suggesting that targeting FPN may have the therapeutic potential for treating NAFLD and related disorders.

Cyanobacterial bioreporter of nitrate bioavailability in aquatic ecosystems.

The water eutrophication, resulting from the discharge of industrial and agricultural wastewater, leads to ecological degradation. However, to date, how to assess and manage the risks of water pollution, especially nitrogen pollution, remains a particularly noteworthy issue. Nitrate, the most important nitrogen compound, has become a bottleneck restricting total nitrogen management. The development of bioreporters monitoring nitrate pollution contributes to the estimation of water quality, especially the availability of nutrients. In this study, we obtained 9 bioreporters from 40 cyanobacterial derivatives which were constructed based on different hosts, copy numbers, and sensing elements and evaluated the performance of bioreporters. The results showed that single-celled Synechocystis was more sensitive to nitrate than filamentous Anabaena, that the reporter gene luxABCDE responded faster than sfgfp in most bioreporters, and that relatively medium-copy plasmid improved the performance of sensing elements. Nine bioreporters performed well in bioavailable nitrate detection, of which AD-AS-X and AR-NI-X, activated by nitrate repletion, had the shortest response time (2 h) and the widest response range (20-800 µM), respectively. Moreover, SR-GLN-SG, activated by nitrate deficiency, exhibited the best linear response (R2 = 0.998). After parameter optimization, exponential growth phase bioreporters, culture temperature of 30 °C, sample volume of 200 µL were determined as optimal monitoring conditions. We found that common water contaminants (copper, cadmium, and phosphorus) had no impact on the performance of bioreporters, indicating the stability of bioreporters. Six out of 9 bioreporters, especially the SR-NB-X, were highly effective in detecting the bioavailable nitrate in wastewater sample. This study provides valuable references for developing more cyanobacterial bioreporters and their practical application in nitrate detection.

Sex Difference is a Determinant of Gut Microbes and Their Metabolites SCFAs/MCFAs in High Fat Diet Fed Rats.

There are gender differences in obesity and related metabolic diseases, but the mechanism of these differences has not been elucidated. Gut microbiota has been recently recognized as a pivotal determinant of obesity and related diseases. The aim of the present study was to investigate sex differences in gut microbiota and its metabolites in an obesity rat model induced by prolonged high-fat-diet (HFD) feeding. In this study, male and female Sprague-Dawley rats were fed normal chow or HFD for 16 weeks (n = 8 for each group). We found that comparing with male rats on HFD (MHFD), female rats on HFD (FHFD) gained more body weight percentage, while had lower body weight gain efficiency and less severity of hepatic steatosis. HFD induced decreased taxon diversity and richness of gut microbiota, and FHFD group had even lower diversity than MHFD group. Among key genera, HFD induced increased Bilophila in male rats but not in female rats. Compared with the MHFD group, FHFD group possessed increases of Akkermansia and Murimonas, and decreases of Acetanaerobacterium, Bacteroides, Bilophila, Blautia and Romboutsia. The levels of total SCFAs in colon contents were increased in tendency in HFD-fed rats of both sexes. FHFD group had increased propionate and decreased ratio of acetate to propionate and butyrate than MHFD group. For MCFAs, HFD induced increases in undecanoic acid and lauric acid in female rats but not in males. In conclusion, HFD induced sex-related alterations in gut microbiome and short/medium-chain fatty acids in rats.

Chronic constant light exposure aggravates high fat diet-induced renal injury in rats.

Obesity-related kidney disease is now recognized as a global health issue, with a substantial number of patients developing progressive renal failure and end-stage renal disease. Interestingly, recent studies indicate light pollution is a novel environmental risk factor for chronic kidney disease. However, the impact of light pollution on obesity-related kidney disease remains largely unknown, with its underlying mechanism insufficiently explained. Renal hypoxia induced factor 1α (HIF1α) is critical in the development of glomerulosclerosis and renal fibrosis. The present study explored effects of constant light exposure on high fat diet (HFD) -induced renal injury and its association with HIF1α signal pathway. Thirty-two male Sprague Dawley rats were divided into four groups according to diet (HFD or normal chow diet) and light cycles (light/dark or constant light). After 16 weeks treatment, rats were sacrificed and pathophysiological assessments were performed. In normal chow fed rats, constant light exposure led to glucose abnormalities and dyslipidemia. In HFD fed rats, constant light exposure exacerbated obesity, glucose abnormalities, insulin resistance, dyslipidemia, renal functional decline, proteinuria, glomerulomegaly, renal inflammation and fibrosis. And, constant light exposure caused an increase in HIF1α and a decrease in prolyl hydroxylase domain 1 (PHD1) and PHD2 expression in kidneys of HFD-fed rats. Then, we demonstrated that BMAL1 bound directly to the promoters of PHD1 in mouse podocyte clone 5 cell line (MPC5) by ChIP assays. In conclusion, chronic constant light exposure aggravates HFD-induced renal injuries in rats, and it is associated with activation of HIF1α signal pathway.

Constant light exposure alters gut microbiota and short-/medium-chain fatty acids and aggravates PCOS-like traits in HFD-fed rats.

OBJECTIVE: This study investigated the effects of constant light exposure on polycystic ovary syndrome (PCOS)-like endocrine and metabolic changes in high-fat diet (HFD)-fed rats and to elucidate the related microbiotic mechanisms. METHODS: A total of 32 female Sprague-Dawley rats were divided into four groups (n = 8 each): rats on a normal chow diet with standard light-dark cycle, rats on a normal chow diet with constant light exposure, rats on an HFD with standard light-dark cycle, and rats on an HFD with constant light exposure. After 16 weeks of treatment, changes in anthropometric parameters, estrous cycle, hormone profiles, ovarian pathology, and gut microbiota and short-/medium-chain fatty acids in colon contents were assessed. RESULTS: Constant light exposure aggravated PCOS-like phenotypes in HFD-fed rats, such as hyperandrogenism, disrupted estrous cycle, and polycystic ovaries. Additionally, constant light exposure and an HFD synergized to decrease α-diversity of gut microbiota, create a reduced abundance of Ruminococcus genus, and create an increased abundance of Firmicutes and the Firmicutes/Bacteroidetes ratio. In HFD-fed rats, the group with constant light exposure had an increase in propionate acid and a decrease in total medium-chain fatty acids in colon contents compared with the standard light-dark cycle group. CONCLUSIONS: Constant light exposure causes gut dysbiosis, alters production of short- and medium-chain fatty acids, and aggravates PCOS-like traits in HFD-fed rats.

Constant Light Exposure Alters Gut Microbiota and Promotes the Progression of Steatohepatitis in High Fat Diet Rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant health concern worldwide. With the progression of urbanization, light pollution may be a previously unrecognized risk factor for NAFLD/NASH development. However, the role of light pollution on NAFLD is insufficiently understood, and the underlying mechanism remains unclear. Interestingly, recent studies indicate the gut microbiota affects NAFLD/NASH development. Therefore, the present study explored effects of constant light exposure on NAFLD and its related microbiotic mechanisms. MATERIALS AND METHODS: Twenty-eight SD male rats were divided into four groups (n = 7 each): rats fed a normal chow diet, and exposed to standard light-dark cycle (ND-LD); rats fed a normal chow diet, and exposed to constant light (ND-LL); rats fed a high fat diet, and exposed to standard light-dark cycle (HFD-LD); and rats on a high fat diet, and exposed to constant light (HFD-LL). Body weight, hepatic pathophysiology, gut microbiota, and short/medium chain fatty acids in colon contents, serum lipopolysaccharide (LPS), and liver LPS-binding protein (LBP) mRNA expression were documented post intervention and compared among groups. RESULT: In normal chow fed groups, rats exposed to constant light displayed glucose abnormalities and dyslipidemia. In HFD-fed rats, constant light exposure exacerbated glucose abnormalities, insulin resistance, inflammation, and liver steatohepatitis. Constant light exposure altered composition of gut microbiota in both normal chow and HFD fed rats. Compared with HFD-LD group, HFD-LL rats displayed less Butyricicoccus, Clostridium, and Turicibacter, butyrate levels in colon contents, decreased colon expression of occludin-1 and zonula occluden-1 (ZO-1), and increased serum LPS and liver LBP mRNA expression. CONCLUSION: Constant light exposure impacts gut microbiota and its metabolic products, impairs gut barrier function and gut-liver axis, promotes NAFLD/NASH progression in HFD rats.

Nucleation Control-Triggering Cocrystal Polymorphism of Charge-Transfer Complexes Differing in Physical and Electronic Properties.

Binary charge-transfer complex polymorphs composed of perylene and 4,8-bis(dicyanomethylene)-4,8-dihydrobenzo-[1,2-b:4,5-b']-dithiophene (DTTCNQ) were synthesized separately via a simple artificial nucleation-tailoring method, in both macroscopic and microscopic cocrystal engineering manners. The two polymorphs were testified to be independently thermosalient in the solid state, and the specific self-assembly derived from homogeneous or heterogeneous nucleation by assistance of governable thermodynamic/kinetic drive, leading to a change in the ordered p-n stacking structure. The as-prepared polymorphic microcrystals afforded a significantly varied (opto)electronic property: high n-type transporting and good photoresponsivity for ß-complex, and ambipolar transporting with ignorable photoresponsivity for α-complex, attributing to the different charge-transfer and supramolecular alignment. This work provides us a new route to the exploitation of donor-acceptor complex family, making it possible to develop functional materials and devices based on variable supramolecular binary structures.

Effects of constant light exposure on sphingolipidomics and progression of NASH in high-fat-fed rats.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a growing public health concern worldwide. With the progression of urbanization, light pollution is becoming an inevitable risk factor for NAFLD. However, the role of light pollution on NAFLD is insufficiently understood, and the underlying mechanism remains unclear. The present study explored effects of constant light exposure on NAFLD and elucidated its related mechanisms. METHODS: Thirty-two male Sprague Dawley rats were divided into four groups (n = 8 each): (i) rats on a normal diet exposed to standard light-dark cycle (ND-LD); (ii) rats on a normal diet exposed to constant light (ND-LL); (iii) rats on a high-fat diet exposed to standard light-dark cycle (HFD-LD); and (iv) and rats on a high-fat diet exposed to constant light (HFD-LL). After 12 weeks of treatment, rats were sacrificed and pathophysiological assessments were performed. Targeted lipidomics was used to measure sphingolipids, including ceramides, glucosylceramides, and lactosylceramides, sphingomyelins, and sphingosine-1-phosphates in plasma and liver tissues. RESULTS: In normal chow rats, constant light exposure led to glucose abnormalities and dyslipidemia. In high-fat-fed rats, constant light exposure exacerbated glucose abnormalities, dyslipidemia, insulin resistance, and inflammation and aggravated steatohepatitis. Compared with HFD-LD rats, HFD-LL had decreased plasma sphingosine-1-phosphate and elevated liver concentrations of total ceramide and specific ceramide species (ceramide d18:0/24:0, ceramide d18:1/22:0, ceramide d18:1/24:0, and ceramide d18:1/24:1), which were associated with increased hepatocyte apoptosis. CONCLUSIONS: Constant light exposure causes dysregulation of sphingolipids and promotes steatohepatitis in high-fat-fed rats.