Rosiglitazone improves survival and hastens recovery from pancreatic inflammation in obese mice.
Rosiglitazone improves survival and hastens recovery from pancreatic inflammation in obese mice.
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DOI：
10.1371/journal.pone.0040944
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fantuzzi G
中科院分区：
文献类型：
--
作者：
Pini M;Rhodes DH;Castellanos KJ;Cabay RJ;Grady EF;Fantuzzi G
肥胖增加急性胰腺炎(AP)的严重程度的机制尚不清楚。我们研究了PPAR-γ激动剂罗格列酮(RGZ，饮食中0.01%)对低脂饮食(LFD)和高脂饮食(HFD)喂养的雄性C57BL6小鼠由IL-12+IL-18诱导的AP严重程度的影响。在无AP的LFD和HFD小鼠中，RGZ显著增加体重和脂肪百分比，显著上调脂联素并抑制红细胞生成。在患有AP的HFD小鼠中，RGZ显著提高了存活率并加速了胰腺炎症的恢复，评估结果是：AP后第7天，显著改善了胰腺组织学，减少了内脏脂肪组织的皂化，并减轻了对红细胞生成的抑制。这与HFD+RGZ小鼠循环和胰腺相关的IL-6、Galectin-3、Osteopontin和TIMP-1水平显著降低有关，尤其是在AP后第7天。在患有AP的LFD小鼠中，RGZ显著加重了胰腺内腺泡和脂肪坏死以及内脏脂肪皂化的程度，而不影响疾病严重程度或炎症的其他参数。在HFD和HFD+RGZ小鼠中，AP的诱导导致脂联素水平在第7天受到主要抑制。总而言之，尽管RGZ显著增加了肥胖小鼠的肥胖度，但它可以防止肥胖小鼠发生严重的AP，这表明可以通过改善代谢和炎症环境将肥胖与AP的严重程度分开。然而，RGZ恶化了LFD小鼠AP严重程度的选择性参数。
Obesity increases severity of acute pancreatitis (AP) by unclear mechanisms. We investigated the effect of the PPAR-gamma agonist rosiglitazone (RGZ, 0.01% in the diet) on severity of AP induced by administration of IL-12+ IL-18 in male C57BL6 mice fed a low fat (LFD) or high fat diet (HFD), under the hypothesis that RGZ would reduce disease severity in HFD-fed obese animals. In both LFD and HFD mice without AP, RGZ significantly increased body weight and % fat mass, with significant upregulation of adiponectin and suppression of erythropoiesis. In HFD mice with AP, RGZ significantly increased survival and hastened recovery from pancreatic inflammation, as evaluated by significantly improved pancreatic histology, reduced saponification of visceral adipose tissue and less severe suppression of erythropoiesis at Day 7 post-AP. This was associated with significantly lower circulating and pancreas-associated levels of IL-6, Galectin-3, osteopontin and TIMP-1 in HFD + RGZ mice, particularly at Day 7 post-AP. In LFD mice with AP, RGZ significantly worsened the degree of intrapancreatic acinar and fat necrosis as well as visceral fat saponification, without affecting other parameters of disease severity or inflammation. Induction of AP lead to major suppression of adiponectin levels at Day 7 in both HFD and HFD + RGZ mice. In conclusion, RGZ prevents development of severe AP in obese mice even though it significantly increases adiposity, indicating that obesity can be dissociated from AP severity by improving the metabolic and inflammatory milieu. However, RGZ worsens selective parameters of AP severity in LFD mice.
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DOI：
10.1152/ajpendo.00219.2010
发表时间：
2011-01-01
影响因子：
5.1
作者：
Hsiao, Gene;Chapman, Justin;Sears, Dorothy D.
通讯作者：
Sears, Dorothy D.
影响因子：
3.8
作者：
Pini, Maria;Rhodes, Davina H.;Fantuzzi, Giamila
通讯作者：
Fantuzzi, Giamila
影响因子：
24.5
作者：
Araki, H.;Nishihara, T.;Shimomura, I.
通讯作者：
Shimomura, I.
影响因子：
4.3
作者：
Konturek, Peter C.;Dembinski, Artur;Konturek, Stanislaw J.
通讯作者：
Konturek, Stanislaw J.
影响因子：
11.2
作者：
Bao, Bin;Wang, Zhiwei;Li, Yiwei;Kong, Dejuan;Ali, Shadan;Banerjee, Sanjeev;Ahmad, Aamir;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.