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RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice
In this study, we performed RNA-sequencing (RNA-seq) analysis with liver tissues to investigate global gene expression among liver-specific Phb1−/−, Phb1+/−, and WT mice, focusing on the differentially expressed (DE) genes between Phb1+/− and WT. When 78 DE genes were analyzed for biological functions, using ingenuity pathway analysis (IPA) tool, lipid metabolism-related genes, including insulin receptor (Insr), sterol regulatory element-binding transcription factor 1 (Srebf1), Srebf2, and SREBP cleavage-activating protein (Scap) appeared to be downregulated in liver-specific Phb1+/− compared with WT. Diseases an...
Source: Frontiers in Physiology - September 3, 2021 Category: Physiology Source Type: research

Decreased IFT88 expression with primary cilia shortening causes mitochondrial dysfunction in cisplatin-induced tubular injury
Am J Physiol Renal Physiol. 2021 Aug 2. doi: 10.1152/ajprenal.00673.2020. Online ahead of print.ABSTRACTThe relevance of primary cilia shortening in kidney disease and its pathomechanism are largely unknown. Tubular damage in acute kidney injury (AKI) is strongly associated with mitochondrial dysfunction. Thus, we investigated the interaction between primary cilia and mitochondria in cisplatin-induced AKI mouse models. We observed that the expression of intraflagellar transport 88 (IFT88), a ciliary maintenance protein, was decreased in the renal cortex following tubular damage due to cisplatin-induced AKI. This result was...
Source: American Journal of Physiology. Renal Physiology - August 2, 2021 Category: Physiology Authors: Rie Fujii Sho Hasegawa Hiroshi Maekawa Tsuyoshi Inoue Kentaro Yoshioka Rie Uni Yoichiro Ikeda Masaomi Nangaku Reiko Inagi Source Type: research

Hypoxia exacerbates non-alcoholic fatty liver disease via HIF-2 α/PPARα pathway.
This study aimed to investigate whether hypoxia can affect non-alcoholic fatty liver disease (NAFLD) progression and the associated mechanisms, specifically regarding the HIF-2α / PPARα pathway in vitro and vivo. Recent studies have reported that, compared with HIF-1α, HIF-2α has different effects on lipid metabolism. We propose hypoxia may exacerbate NAFLD by the HIF-2α upregulation-induced suppression of PPARα in the liver. To verify this hypothesis, a steatotic human hepatocyte (L02) cell line treated with free fatty acids and a mouse model of NAFLD fed a high-fat diet were used. Steatotic hepatocytes were treated...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 19, 2019 Category: Physiology Authors: Chen J, Chen J, Fu H, Li Y, Wang L, Luo S, Lu H Tags: Am J Physiol Endocrinol Metab Source Type: research

Resveratrol protects against nonalcoholic fatty liver disease by improving lipid metabolism and redox homeostasis via the PPAR α pathway
This study investigated the preventive and therapeutic effects of RSV on high-fat diet (HFD)-induced NAFLD in rats and palmitate acid (PA)-induced hepatocyte steatosis in HepG2 cells. Hepatocytes were incubated with inhibitors of peroxisome proliferator-activated receptor α (PPARα) or short interfering RNAs (siRNAs) targeting PPARα, AMP-activated protein kinase (AMPK), and protein kinase A (PKA) to determine the underlying mechanisms. We found that RSV noticeably ameliorated HFD-induced hepatic steatosis in rats and inhibited PA-induced lipid accumulation in HepG2 cells. Moreover, RSV improved lipid metabolism, enhanced...
Source: Applied Physiology, Nutrition, and Metabolism - June 6, 2019 Category: Physiology Authors: Yujie Huang Hedong Lang Ka Chen Yong Zhang Yanxiang Gao Li Ran Long Yi Mantian Mi Qianyong Zhang Source Type: research

Detailed Dissection of UBE3A-Mediated DDI1 Ubiquitination
Discussion Poly-ubiquitinated proteins targeted for degradation might be recognized directly by proteasomal receptors or by proteasomal shuttling proteins. The first shuttling proteins – Ddi1, Rad23 and Dsk2 – were identified and characterized in Saccharomyces cerevisiae (Lambertson et al., 1999; Kaplun et al., 2005). Proteasomal shuttles contain an N-terminal ubiquitin-like (UBL) domain that interacts with the 26S proteasome (Finley, 2009), and a C-terminal ubiquitin-binding domain domain (UBD) that binds to ubiquitin or poly-ubiquitin chains (Bertolaet et al., 2001). When ubiquitinated, substrates are capt...
Source: Frontiers in Physiology - May 2, 2019 Category: Physiology Source Type: research

Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway
Conclusion In conclusion, the present study demonstrated that autophagy was involved in relieving the effects of TSF against NAFLD, which were mediated by the AMPK/SIRT1 pathway (Figure 7D). These findings may improve our current understanding of the role of TSF in treating hepatic steatosis and provide an experimental basis for the clinical application of TSF in NAFLD and its related metabolic syndrome. Ethics Statement This study was carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Ethics Co...
Source: Frontiers in Physiology - April 25, 2019 Category: Physiology Source Type: research

FGF21 as Modulator of Metabolism in Health and Disease
In conclusion, FGF21 belongs to a promising class of cytokines that are induced in response to stress and that can be used as a drug, drug target, or through a biomarker, depending on the physio-pathological context. All these findings will become clear when FGF21 will be used as a therapeutic molecule, exploiting the beneficial effects of FGF21 for treating metabolic disease or when it will be blocked to ameliorate disease progression and the onset of disease. Author Contributions CT and MS wrote the manuscript. VR contributed to the discussion. Funding This work was supported from the AFM-Telethon (19524), Italian Mi...
Source: Frontiers in Physiology - April 16, 2019 Category: Physiology Source Type: research

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