应用神经肽YY5受体反义基因治疗肥胖大鼠高leptin血症效果的探讨

目的：探讨神经肽Y Y5（NPY Y5）受体反义基因治疗对肥胖大鼠高leptin血症的改善作用及其机制。方法：建立高营养饮食诱导的肥胖大鼠模型，侧脑室插管后注射NPY Y5受体反义、正义、我寡核苷酸或生理盐水，观察大鼠腹膜后与生殖器周围脂肪组织湿重的变化，并采用ELISA双抗体心法测定血清leptin水平、放免法测定血清胰岛素水平。结果：（1）高营养饮食诱导的肥胖模型大鼠血清leptin水平、血清胰岛素水平及两部位脂肪组织湿重明显高于正常大鼠；（2）经NPY Y5受体反义寡核苷酸干预后，肥胖大鼠血清leptin水平、血清胰岛素水平、血清胰岛素水平、腹膜后脂肪组织湿重均明显降低，但生殖器周围脂肪组织湿重无明显变化；（3）大鼠血清leptin水平、血清胰岛素水平、腹膜后脂肪组织湿重间均存在一定的正相关关系。结论：侧脑室注射NPY Y5受体反义寡核苷酸可显著改善肥胖大鼠的高leptin血症，推测其机制可能与大鼠进食行为改变、腹膜后脂肪组织减少、血清胰岛素水平下降等因素有关。     

应用神经肽Y Y5受体反义基因治疗肥胖大鼠高Leptin血症效果的探讨

目的 :探讨神经肽YY5 (NPYY5 )受体反义基因治疗对肥胖大鼠高Leptin血症的改善作用及其机制。方法 :建立高营养饮食诱导的肥胖大鼠模型 ,侧脑室插管后注射NPYY5受体反义、正义、错义寡核苷酸或生理盐水 ,观察大鼠腹膜后与生殖器周围脂肪组织温重的变化 ,并采用ELISA双抗体夹心法测定血清Leptin水平、放免法测定血清胰岛素水平。结果 :①高营养饮食诱导的肥胖模型大鼠血清Leptin水平、血清胰岛素水平、腹膜后脂肪湿重明显高于正常大鼠 ;②经NPYY5受体反义寡核苷酸干预后 ,肥胖大鼠血清Leptin水平、血清胰岛素水平、腹膜后脂肪组织温重均明显降低 ,但生殖器周围脂肪组织温重无明显变化 ;③大鼠血清Leption水平、血清胰岛素水平、腹膜后脂肪组织温重间均存在一定的正相关关系。结论 :侧腔室注射NPYY5受体反义寡核苷酸可显著改善肥胖大鼠的高Leptin血症 ,推测其机制可能与大鼠进食行为改变、腹膜后脂肪组织减少、血清胰岛素水平下降等因素有关     

Tributyltin causes obesity and hepatic steatosis in male mice

Organotin compounds such as tributyltin (TBT) have been used worldwide in agriculture and industry as biocides, heat stabilizers, and chemical catalysts. However, few studies addressing the effects of TBT on growth and metabolism have been reported. This study was conducted to investigate the effects of TBT at low doses (0.5, 5, and 50 μg/kg) on body weight gain in male mice exposed as from puberty and to determine the alterations in related hormones. The results showed that exposure to TBT for 45 days resulted in an increase in body weight gain and hepatic steatosis accompanied with hyperinsulinemia and hyperleptinemia. Reduction of hepatic adiponectin levels in a dose‐dependent manner was related to the lipid increase in the liver. These results suggest that chronic and repeat exposure to low doses of TBT can result in obesity and hepatic steatosis and induce the occurrence of insulin and leptin resistance. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 79–85, 2011.     

Serum leptin level as a diagnostic and prognostic marker in infectious diseases and sepsis: A comprehensive literature review

Background:Infections and sepsis are common causes of morbidity and mortality, with an increasing incidence worldwide. Leptin is involved in the inflammatory process and may modulate the cytokine production, immune cell proliferation and endothelial function. There are conflicting results regarding alterations of leptin levels in infectious diseases and the outcome from sepsis.The aim of the current article is to provide an overview of the medical literature on the correlations between variations of leptin levels and infectious diseases and sepsis.Methods:We performed an extensive literature search in PubMed and Google Scholar databases, using keywords to identify articles related to leptin in infectious diseases and sepsis. Searches were referenced using medical subject headings that included “leptin,” “adipokines,” “sepsis,” “infectious diseases,” “leptin deficiency,” “leptin resistance” or “hyperleptinemia.” The language of publication, journal, or country were not included as limitation criteria.Articles or abstracts containing adequate information, such as age, sex, anthropometric indices, clinical presentation, comorbidities, and management were included in the study, whereas articles with insufficient clinical and demographic data were excluded. We assessed the quality of the studies selected.The final review of all databases was conducted on June 18, 2020.Results:We find the results from the current review to be of great importance due to the possible therapeutic role of leptin analogs in states of leptin deficiency associated with infectious diseases or sepsis.In hyperleptinemia, a therapeutic plan for obtaining leptin neutralization also needs further investigations. This could lead to the reduction of proinflammatory responses.There is a need for further studies to demonstrate the specificity and sensitivity of leptin in the early diagnosis of sepsis and the need to measure serum leptin levels in routine evaluation of the critical patient.Conclusion:The multiple effects of leptin are of growing interest, but further studies are needed to elucidate the role of leptin signalling in infectious diseases and sepsis. Because very few human studies are reported, we recommend the need for further research.Better understanding of the pathophysiology of sepsis and the implication of circulating total leptin in this process could help physicians in managing this life-threatening condition.     

Stimulation of prolactin secretion by chronic, but not acute, administration of leptin in the rat

Leptin, the product of obese (ob) gene, has been reported to affect the secretion of all six anterior pituitary hormones, but data are especially scarce regarding the interplay between leptin and prolactin (PRL). Thus, in this study we examined and compared in vivo the effects of acute and chronic administrations of recombinant mouse leptin on PRL secretion in male rats. Normally-fed and 3-day-fasted rats received an intraperitoneal bolus injection of leptin [1.0 mg/kg body weight (BW)] or vehicle only. The leptin treatment was without effect on plasma PRL levels up to 5 h postadministration. Food deprivation for 3 days significantly decreased both PRL and leptin levels. This decrease in plasma PRL was prevented by a 3-day constant infusion of 75 microg/kg BW/day of leptin, which maintained plasma leptin levels similar to those of normally-fed rats. The administration of three times the higher dose of leptin (225 microg/kg BW/day) to fasted rats led to further increases in both PRL and leptin in the plasma. Thus, a dose-dependent stimulatory effect of chronic leptin treatment on PRL secretion was indicated. This study demonstrates that chronic, but not acute, administration of leptin stimulates PRL secretion in the rat.     

c-Jun acts downstream of PI3K/AKT signaling to mediate the effect of leptin on methionine adenosyltransferase 2B in hepatic stellate cells in vitro and in vivo

Obese patients, often accompanied by hyperleptinemia, are prone to develop liver fibrosis. A large body of data including the results from human studies suggested the promotion role of leptin, an adipocyte-derived hormone, in liver fibrosis. Hepatic stellate cell (HSC) activation, a crucial step in liver fibrogenesis, requires global reprogramming of gene expression which is regulated by multiple mechanisms including epigenetic regulation such as methylation of DNA. S-Adenosylmethionine is a principal biological methyl donor and its biosynthesis is catalyzed by a methionine adenosyltransferase (MAT) such as MATII. MATII consists of the catalytic subunit MAT2A and regulatory subunit MAT2B which are essential for HSC activation. The present research investigated the effect of leptin on the expression of Mat2b in HSCs in vitro and in a leptin-deficient mouse model. Results demonstrated that leptin significantly increased Mat2b expression. Leptin-induced Mat2b expression required the PI3K/AKT signaling pathway. c-Jun, a component of activator protein (AP1), was phosphorylated by leptin-induced PI3K/AKT signaling and thus potentiated its binding to the element around −964 bp in the Mat2b promoter. MAT2B was involved in leptin-induced HSC activation and liver fibrosis in a leptin-deficient mouse model. These results might broaden understanding of the mechanisms underlying the liver fibrogenesis in obese patients with hyperleptinemia. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

鱼油摄入对肥胖大鼠脂肪组织、瘦素表达和胰岛素水平的影响

目的探讨鱼油摄入对肥胖大鼠体重增量、脂肪组织、瘦素基因表达、血清瘦素及胰岛素水平的影响。方法雄性Wistar大鼠在高脂(猪油20%WT/WT)饮食8 w后,以体重比对照组重30g及以上(约1个标准差)为标准分出肥胖大鼠,并按体重随机分为两组:猪油组(猪油20/100 WT/WT)和鱼油组(鱼油20/100WT/WT),保留对照组,分别饲以相应饲料,继续饲养4w。腹腔麻醉,心脏穿刺取血并分离血清,测血清瘦素及胰岛素水平;处死大鼠,分离腹膜后、附睾脂肪组织,称湿重,做腹膜后脂肪组织切片,以目镜测微计测脂肪细胞直径;RT-PCR检测脂肪组织瘦素mRNA。结果 (1)鱼油组大鼠体重增量、腹膜后、附睾脂肪组织湿重、脂肪细胞体积显著低于猪油组;其脂肪组织瘦素mRNA表达水平、血清瘦素、胰岛素水平均有降低趋势,但未达到统计学意义上的显著差异。(2)猪油、鱼油两组大鼠血清瘦素水平与血清胰岛素水平均呈显著的相关关系。结论鱼油饮食4w能显著降低肥胖大鼠体重增量、脂肪组织含量,但未能显著降低脂肪组织瘦素mRNA水平、血清瘦素及胰岛素水平。[营养学报,2013,35(2):146-149]