CD36 regulates diurnal glucose metabolism and hepatic clock to maintain glucose homeostasis in mice

Summary: The mammalian circadian clock and glucose metabolism are highly interconnected, and disruption of this coupling is associated with multiple negative health outcomes. Liver is the major source of endogenous glucose production and liver clock is one of the most vital peripheral clock systems. We demonstrate that fatty acid translocase (CD36) is expressed rhythmically in mouse liver and autonomously modulates the diurnal oscillations of liver clock and glucose homeostasis. CD36 knockout in hepatocytes inhibits the relay of insulin signaling and provokes FoxO1 nuclear shuttling, consequently increasing Per1 nuclear expression. Moreover, FoxO1 can activate the central clock gene Per1 at the transcriptional level. These changes lead to a disrupted clock oscillation and behavioral rhythm. Our study first reveal that CD36 is a key regulator of the circadian oscillator and its deficiency may cause liver clock disruption, which aggravates the imbalance of glucose homeostasis and contribute to augmentation and progression of metabolic disease

Loss of Splicing Factor SRSF3 Impairs Lipophagy Through Ubiquitination and Degradation of Syntaxin17 in Hepatocytes

Lipid accumulation in hepatocytes is the distinctive characteristic of nonalcoholic fatty liver disease. Serine/arginine-rich splicing factor 3 (SRSF3) is highly expressed in the liver and expression decreases in high-fat conditions. However, the role of SRSF3 in hepatic lipid metabolism needs to be clarified. Here, we showed that loss of SRSF3 was associated with lipid accumulation. We determined that SRSF3 regulated lipophagy, the process of selective degradation of lipid droplets by autophagy. Mechanistically, loss of SRSF3 impaired the fusion of the autophagosome and lysosome by promoting the proteasomal degradation of syntaxin 17 (STX17), a key autophagosomal SNARE protein. We found that ubiquitination of STX17 was increased and upregulation of seven in absentia homolog 1 was responsible for the increased posttranslational modification of STX17. Taken together, our data primarily demonstrate that loss of SRSF3 weakens the clearance of fatty acids by impairing lipophagy in the progression of nonalcoholic fatty liver disease, indicating a novel potential therapeutic target for fatty liver disease treatment

Disegno e modalit\ue0 di realizzazione della survey CHIP (CHinese In Prato)

Following the rapid economic development, China is experiencing a progressive increase in the incidence of cardiovascular (CV) events and in the prevalence of CV risk factors. According to recent estimations, the prevalence of diabetes sharply increased from 1% in 1980 to 11% in 2013. Migration from China to Europe is now mainly concentrated in Countries of the Southern Europe, e.g., Italy and Spain. The largest Chinese community living in Italy is now settled in Prato, being also one of the largest Chinese community in Europe. Local authorities estimate a number of Chinese citizens living in Prato of over 40,000 individuals, including illegal immigrants. The availability of reliable data on the health needs of Chinese population is thus a recognised priority for the local health system. The creation of a participatory research where Chinese population directly participates in the formation of a group of citizens involved in designing and conducting the survey allows to overcome difficulties due to the lack of official demographic files. Secondly, and most important, this approach makes it possible to effectively pass a prevention message to an elusive population. The purpose of the CHIP (CHinese In Prato) survey is to investigate the prevalence of diabetes and cardiovascular risk factors among Chinese immigrants. Recruitment procedure was started on 8th July 2014