Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013911 (emaciation)
 1,059 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cachexia in cancer is characterized by progressive emaciation involving depletion of host adipose tissue stores, the molecular mechanism of which remains largely unknown. In this study, we have attempted to clarify the biologic characteristics of lipid-depleting factor in a mouse cachexia model. Utilizing differentiated 3T3-L1 adipocytes, we established an assay method quantifying the lipid-depleting activity in plasma derived from colon-26-inoculated mice and then analyzed the associated molecular mechanism. Injection (s.c.) of a mouse colon adenocarcinoma cell line, colon-26 clone 20, induced cachexia, as evidenced by progressive weight loss. Addition of clone 20-derived cachexigenic, but not clone 5-derived noncachexigenic, plasma to the culture medium of differentiated 3T3-L1 adipocytes reduced the TG content in cultured cells. The ability of the introduced plasma to induce TG loss in 3T3-L1 cells paralleled the body weight changes of tumor-inoculated host mice. Clone 20 plasma, but not clone 5 plasma or recombinant IL-6, elicited lipolytic activity, which induced glycerol release from 3T3-L1 cells. Addition of clone 20 plasma to cultured 3T3-L1 adipocytes reduced TG synthesis from [(14)C]-glucose compared to clone 5 plasma, indicating that the lipid-depleting activity resulting from addition of clone 20 plasma depended not only on induction of lipolysis but also on inhibition of lipogenesis. Addition of clone 20 plasma to cultured 3T3-L1 adipocytes reduced the quantity of mature SREBP-1 in the nucleus of 3T3-L1 cells without affecting PPAR-gamma and C/EBP-alpha. Although TNF-alpha induced apoptosis in 3T3-L1 cells, clone 20 plasma did not. These results suggest that the lipid-depleting factor in clone 20 plasma is different from either IL-6 or TNF-alpha, and that this factor interfered with not only lipolysis but also lipogenesis through SREBP-1 of 3T3-L1 adipocytes.
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PMID:Molecular analysis of lipid-depleting factor in a colon-26-inoculated cancer cachexia model. 1220 86

The pathogenesis of fatty liver disease remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis in zebrafish by liver specific expression of Hepatitis B virus X protein (HBx). Transgenic zebrafish lines, GBXs, which selectively express the GBx transgene (GFP-fused HBx gene) in liver, were established. GBX Liver phenotypes were evaluated by histopathology and molecular analysis of fatty acid (FA) metabolism-related genes expression. Most GBXs (66-81%) displayed obvious emaciation starting at 4 months old. Over 99% of the emaciated GBXs developed hepatic steatosis or steatohepatitis, which in turn led to liver hypoplasia. The liver histology of GBXs displayed steatosis, lobular inflammation, and balloon degeneration, similar to non-alcoholic steatohepatitis (NASH). Oil red O stain detected the accumulation of fatty droplets in GBXs. RT-PCR and Q-rt-PCR analysis revealed that GBx induced hepatic steatosis had significant increases in the expression of lipogenic genes, C/EBP-alpha, SREBP1, ChREBP and PPAR-gamma, which then activate key enzymes of the de novo FA synthesis, ACC1, FAS, SCD1, AGAPT, PAP and DGAT2. In addition, the steatohepatitic GBX liver progressed to liver degeneration and exhibited significant differential gene expression in apoptosis and stress. The GBX models exhibited both the genetic and functional factors involved in lipid accumulation and steatosis-associated liver injury. In addition, GBXs with transmissible NASH-like phenotypes provide a promising model for studying liver disease.
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PMID:Increase of hepatic fat accumulation by liver specific expression of Hepatitis B virus X protein in zebrafish. 2041 98