7-Hydroxyflavone improves nonalcoholic fatty liver disease by acting on STK24.

The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high-fat diet, leading to a decline in quality of life and significant health impairment. 7-Hydroxyflavone (7-HY) is a flavonoid known for its anti-inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7-HY on NAFLD induced by a high-fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid-induced HepG2 cells and C57BL/6 mice on a high-fat diet were utilized as in vitro and in vivo models. In animal experiments, 7-HY was utilized as a dietary supplement. The 15-week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7-HY, compared with NAFLD-associated targets in the GeneCards database. Results indicated 7-HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high-fat diet. Furthermore, 7-HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7-HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7-HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7-HY demonstrated the capacity to alleviate high-fat diet-induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity.

OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.

Single-shot optical imaging with spectrum circuit bridging timescales in high-speed photography.

Single-shot optical imaging based on ultrashort lasers has revealed nonrepetitive processes in subnanosecond timescales beyond the recording range of conventional high-speed cameras. However, nanosecond photography without sacrificing short exposure time and image quality is still missing because of the gap in recordable timescales between ultrafast optical imaging and high-speed electronic cameras. Here, we demonstrate nanosecond photography and ultrawide time-range high-speed photography using a spectrum circuit that produces interval-tunable pulse trains while keeping short pulse durations. We capture a shock wave propagating through a biological cell with a 1.5-ns frame interval and 44-ps exposure time while suppressing image blur. Furthermore, we observe femtosecond laser processing over multiple timescales (25-ps, 2.0-ns, and 1-ms frame intervals), showing that the plasma generated at the picosecond timescale affects subsequent shock wave formation at the nanosecond timescale. Our technique contributes to accumulating data of various fast processes for analysis and to analyzing multi-timescale phenomena as a series of physical processes.