The role of Stat3 signaling in leptin's pleitropic action

Stat3信号在瘦素多效性作用中的作用

基本信息

批准号：
7678533
负责人：
CHRISTOPH BUETTNER
金额：
$ 11.68万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-20 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7678533
关键词：
ADD-1 protein Acute Adenoviruses Adipocytes Adipose tissue Affect Autonomic nervous system Binding Proteins Biological Process Carbohydrates Defect Diazoxide Dominant-Negative Mutation Eating Fatty acid glycerol esters Feeding behaviors Gene Expression Genes Genetic Glucose Gonadotropins Hepatic Hypothalamic structure Infusion procedures Insulin Intake Lead Leptin Mediating Metabolic Pathway Metabolism Methodology Mitochondria Molecular Mus Nonesterified Fatty Acids Obesity PPAR gamma Pathway interactions Peptides Peroxisome Proliferator-Activated Receptors Play Potassium Channel Rattus Regulation Regulatory Element Role STAT protein Signal Pathway Signal Transduction Sterols Techniques Tissues Triglycerides Visceral Work base db/db mouse in vivo leptin receptor lipid biosynthesis lipid metabolism mouse model oxidation prevent respiratory subcutaneous tool transcription factor uptake

项目摘要

DESCRIPTION (provided by applicant): Leptin has potent effects on insulin action, carbohydrate and lipid metabolism, which are largely independent of its effects on feeding behavior. With regard to adipocyte metabolism, leptin leads to a depletion of triglyceride content without a concomitant rise in circulating free fatty acids due to an increase in mitochondrial oxidation and the induction of futile metabolic pathways. Our previous work has revealed that leptin controls adipocyte metabolism by central pathways that descend from the medio-basal hypothalamus (MBH), leading to a strong inhibition of lipogenic gene expression in white adipose tissue (WAT). Remarkably, MBH leptin suppresses the expression and activity of two important transcription factors, sterol-regulatory-element-binding protein-1c (SREBPI-c) and peroxisome proliferator activated receptor (PPAR) gamma, independent of circulating glucose or insulin levels. These effects of central leptin on adipocyte metabolism appear not to require intact signal transducer and activator of transcription (Stat3) signaling, whereas leptin's acute effects on food intake, hepatic glucose fluxes and gonadotropin secretion are lost when Stat3 signaling is prevented. The aim of this proposal is to delineate the contributions of hypothalamic leptin signaling in controlling adipocyte metabolism. We hypothesize that Stat3 independent effects of leptin play a major role in the regulation of adipocyte metabolism and thereby regulate body adiposity. These studies should lead to a better understanding of the basic biological processes by which central pathways regulate body adiposity independently of food intake.

描述（由申请人提供）：瘦素对胰岛素作用，碳水化合物和脂质代谢具有有效的影响，这在很大程度上与其对喂养行为的影响无关。关于脂肪细胞代谢，瘦素会导致甘油三酸酯含量的耗竭，而由于线粒体氧化和诱导徒劳的代谢途径的诱导，循环游离脂肪酸的循环游离脂肪酸伴随着增加。我们以前的工作表明，瘦素通过中心途径来控制脂肪细胞代谢，从而从中质下丘脑（MBH）降临，从而导致在白色脂肪组织（WAT）中强烈抑制脂肪生成基因的表达。值得注意的是，MBH瘦素抑制了两个重要的转录因子的表达和活性：固醇调节元素结合蛋白1C（SREBPI-C）和过氧化物酶体增殖物激活受体（PPAR）GAMMA，独立于循环葡萄糖或胰岛素水平。中央瘦素对脂肪细胞代谢的影响似乎不需要完整的信号传感器和转录（Stat3）信号传导的激活因子，而瘦素对食物摄入，肝葡萄糖通量和促性腺激素分泌的急性影响在预防STAT3信号时会丢失。该提案的目的是描述下丘脑瘦素信号在控制脂肪细胞代谢中的贡献。我们假设瘦素的STAT3独立作用在调节脂肪细胞代谢并因此调节身体肥胖中起主要作用。这些研究应该可以更好地理解中心途径独立于食物摄入的基本生物学过程。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

DOI：
10.1289/ehp164
发表时间：
2016-11
期刊：
Environmental health perspectives
影响因子：
10.4
作者：
La Merrill MA;Sethi S;Benard L;Moshier E;Haraldsson B;Buettner C
通讯作者：
Buettner C

The dysregulation of the endocannabinoid system in diabesity-a tricky problem.

DOI：
10.1007/s00109-009-0459-y
发表时间：
2009-07
期刊：
JOURNAL OF MOLECULAR MEDICINE-JMM
影响因子：
4.7
作者：
Scherer, Thomas;Buettner, Christoph
通讯作者：
Buettner, Christoph

Yin and Yang of hypothalamic insulin and leptin signaling in regulating white adipose tissue metabolism.

DOI：
10.1007/s11154-011-9190-4
发表时间：
2011-09
期刊：
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
影响因子：
8.2
作者：
Scherer, Thomas;Buettner, Christoph
通讯作者：
Buettner, Christoph

Hepatic muscarinic acetylcholine receptors are not critically involved in maintaining glucose homeostasis in mice.

DOI：
10.2337/db09-0522
发表时间：
2009-12
期刊：
Diabetes
影响因子：
7.7
作者：
Li JH;Gautam D;Han SJ;Guettier JM;Cui Y;Lu H;Deng C;O'Hare J;Jou W;Gavrilova O;Buettner C;Wess J
通讯作者：
Wess J

Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis.

DOI：
10.1016/j.molcel.2014.10.028
发表时间：
2015-01-08
期刊：
MOLECULAR CELL
影响因子：
16
作者：
Renault, Thibaud T.;Floros, Konstantinos V.;Elkholi, Rana;Corrigan, Kelly-Ann;Kushnareva, Yulia;Wieder, Shira Y.;Lindtner, Claudia;Serasinghe, Madhavika N.;Asciolla, James J.;Buettner, Christoph;Newmeyer, Donald D.;Chipuk, Jerry E.
通讯作者：
Chipuk, Jerry E.