Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity.
Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity.
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DOI：
10.1126/scitranslmed.3002573
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发表时间：
2011-11-02
影响因子：
17.1
通讯作者：
Singh VP
中科院分区：
文献类型：
--
作者：
Navina S;Acharya C;DeLany JP;Orlichenko LS;Baty CJ;Shiva SS;Durgampudi C;Karlsson JM;Lee K;Bae KT;Furlan A;Behari J;Liu S;McHale T;Nichols L;Papachristou GI;Yadav D;Singh VP
肥胖增加了烧伤、严重创伤和急性胰腺炎等急性危重病的不良结局风险。虽然具有更多体脂肪和更高血清细胞因子和脂肪酶的个体更容易遇到问题，但这些特征所起的作用尚不清楚。我们以重症急性胰腺炎为代表性疾病，研究肥胖对局部器官功能和全身过程的影响。在肥胖人群中，我们发现胰腺内脂肪细胞体积的增加与急性胰腺炎时更广泛的胰腺坏死有关，而在肥胖人群中，急性胰腺炎与多系统器官衰竭有关。对胰腺腺泡细胞的体外研究表明，不饱和脂肪酸具有促炎症作用，释放细胞内钙，抑制线粒体复合体I和V，并导致坏死。饱和脂肪酸则没有这种作用。在诱发胰腺炎的肥胖（ob/ob）小鼠中抑制脂解可防止血清不饱和脂肪酸升高，并防止肾损伤、肺损伤、全身性炎症、低钙血症、胰腺坏死减少和死亡率降低。因此，针对不饱和脂肪酸介导的脂毒性的治疗方法可能会减少患有重症急性胰腺炎等危重疾病的肥胖患者的不良后果。
Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.
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影响因子：
6.4
作者：
Carvalho, Marco A.;Zecchin, Karina G.;Graner, Edgard
通讯作者：
Graner, Edgard
影响因子：
7.6
作者：
Duarte-Rojo, A.;Sosa-Lozano, L. A.;Robles-Diaz, G.
通讯作者：
Robles-Diaz, G.
DOI：
10.1016/0005-2760(76)90009-6
发表时间：
1976-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GIUDICELLI, Y;PROVIN, D;NORDMANN, R
通讯作者：
NORDMANN, R
影响因子：
3.6
作者：
Heiss, P.;Bruennler, T.;Hamer, O. W.
通讯作者：
Hamer, O. W.
DOI：
10.1016/j.jchromb.2008.08.009
发表时间：
2008-09-15
期刊：
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
影响因子：
--
作者：
Kangani CO;Kelley DE;Delany JP
通讯作者：
Delany JP