SummaryThe present study was undertaken to investigate the mechanism by which 1 ␣ , 25-dihydroxy-cholecalciferol [1 ␣ ,25-(OH) 2 -VD 3 ] modulates the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes. Treatment with 1 ␣ ,25-(OH) 2 -VD 3 in the presence of insulin, dexamethasone and 3-isobutyl-1-methyl-xanthine significantly inhibited the triacylglycerol accumulation, and mRNA expressions of adipocytokines (adiponectin and tumor necrosis factor-␣ ) and plasminogen activator inhibitor-1 in the piconanomolar concentration range, indicating that 1 ␣ ,25-(OH) 2 -VD 3 under physiological conditions inhibits the differentiation of 3T3-L1 cells. 1 ␣ ,25-(OH) 2 -VD 3 potently reduced the mRNA and/or protein expressions of CCAAT-enhancer binding protein ␣ (C/EBP ␣ ) and peroxisome proliferator-activated receptor ␥ (PPAR ␥ ), and the nuclear translocation of PPAR ␥ . Furthermore, it inhibited the mRNA expression and phosphorylation of extracellular signalregulated kinase (ERK), one of mitogen-activated protein kinases. These results indicate that 1 ␣ ,25-(OH) 2 -VD 3 can be an inhibitor of adipocyte differentiation, and suggest, in addition to C/EBP ␣ and PPAR ␥ , an important role of ERK in mediating 1 ␣ ,25-(OH) 2 -VD 3 -induced alteration in adipocyte differentiation.
Dietary conjugated linoleic acid (CLA) has been reported to exhibit a number of therapeutic effects in animal models and patients, such as anti-hypertensive, anti-hyperlipidemic, anti-arteriosclerotic, anti-carcinogenic, and anti-diabetic effects. However, the underlying mechanism is not well-characterized. In the present study, the effects of cis(c)9, trans(t)11-CLA on the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes were examined. Treatment with c9, t11-CLA in the presence of insulin, dexamethasone, and 3-isobutyl-1-methyl-xanthine (differentiation cocktail) significantly stimulated the accumulation of triacylglycerol. The microscopic observation of cells stained by Oil Red O demonstrated that c9, t11-CLA increases the amount and proportion of small mature adipocytes secreting adiponectin, a benign adipocytokine, when compared to the differentiation cocktail alone. Furthermore, c9, t11-CLA increased bioactive peroxisome proliferator-activated receptor γ (PPARγ) levels in a nuclear extract of 3T3-L1 cells, suggesting the enhancing effect of this fatty acid on the nuclear transmission of PPARγ, a master regulator of adipocyte differentiation, in 3T3-L1 cells. These results suggest that the therapeutic effects of c9, t11-CLA on lifestyle-related diseases are partially due to the enhanced formation of small adipocytes from preadipocytes via PPARγ stimulation.
The Liver Study Group of Hokkaido analyzed a total of 57 patients with non-resectable primary liver cancers, which were treated by intra-arterial adriamycin infusion chemotherapy combined with lipiodol and/or the Gelform embolization of the hepatic arteries. Of the ten patients considered clinical responders, three complete response patients and seven partial response cases were obtained. The overall response rate was 17.5%. The median survival period at each clinical stage was as follows: stage I: 13.0 months, stage II: 16.0 months, stage III: 11.5 months and stage IV: 4.7 months. The common side-effects of this treatment were nausea, vomiting and anorexia. Hematological toxicities were also found, but there was no patient who suffered from severe complications.
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