Asprosin, body weight, and risk of type 2 diabetes in U.S. men and women

美国男性和女性的白脂素、体重和 2 型糖尿病风险

基本信息

批准号：
10374913
负责人：
Atul Chopra
金额：
$ 67.78万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10374913
关键词：
Adipose tissue Adopted Affect African American Appetite Stimulants Biochemical Biochemical Markers Blood - brain barrier anatomy Blood Circulation Blood specimen Body Weight Body Weight Changes Candidate Disease Gene Clinical Coupled Data Desire for food Development Diabetes Mellitus Diagnostic Epidemic Ethnic Origin FBN1 Fasting Follow-Up Studies Food Funding Genes Genetic Genetic Variation Genome Genotype Glucose Gold HIV-Associated Lipodystrophy Syndrome Health Professional Hepatic Hispanic Americans Hormonal Hormones Human Hypoglycemia Hypothalamic structure Immunologics Incidence Insulin Insulin Resistance Investments Life Style Lipodystrophy Longitudinal prospective study Mediating Mendelian randomization Methodology Methods Molecular Mus Mutation Names Non-Insulin-Dependent Diabetes Mellitus Nutritional Obesity Online Mendelian Inheritance In Man Other Genetics Pathogenesis Pathway interactions Patients Plasma Play Population Population Heterogeneity Prevention strategy Process Prospective cohort Protocols documentation Research Personnel Resources Risk Role Sampling Secondary to Standardization Statistical Methods Symptoms Therapeutic Thinness Time United States National Institutes of Health Validation Variant Wiedemann-Rautenstrauch syndrome Woman Women&apos s Health Work blood glucose regulation case control caucasian American clinical phenotype cohort cost efficient density design diabetes risk dietary epidemiology study ethnic diversity falls feeding follow-up genetic predictors genome wide association study genomic data glucose production high risk loss of function loss of function mutation male health men mouse model novel novel diagnostics novel therapeutic intervention obesity development obesity risk obesity treatment prospective rare genetic disorder sex

项目摘要

PROJECT SUMMARY Asprosin, a newly identified glucogenic hormone through study of neonatal progeroid syndrome (NPS, or Marfan lipodystrophy syndrome), may have both therapeutic and diagnostic implications for obesity and diabetes. The gene encoding asprosin, FBN1, has unique extreme 3’ mutations resulting in hypoglycemic symptoms and low plasma insulin levels in a few patients with the rare NPS. Considerable evidence has recently demonstrated asprosin’s direct role in hepatic glucose production modulation, and asprosin immunologic neutralization in the treatment of obesity and diabetes in mouse models. The direct effect of asprosin on type 2 diabetes (T2D) incidence in humans has not been investigated in human populations. The current application aims to investigate the potential causal role of asprosin for obesity and T2D development in two large and high-quality prospective cohorts of men and women. We plan to integrate data on relevant genetic variations, biochemical markers, and clinical phenotypes of obesity and T2D incidence in the national Women’s Health Initiative (WHI) and the men’s Health Professionals Follow-Up Study (HPFS). Both WHI and HPFS are long-term prospective cohorts that have been funded by the NIH with detailed and high-quality dietary, lifestyle, clinical, biochemical, and genomic data, and a large number of well-characterized and validated incident T2D cases using standardized protocol consistently over 20 years of follow-up. All incident T2D cases with existing genetic data and fasting blood samples (n1=2,615) matched by an equal number of controls (n0=2,615) randomly selected from the same WHI cohort of women, and 600 case-control pairs of men (n’=1,200) will be included using the identical nested case- control design. Genotyping and validation analyses will be performed in an additional 1,076 T2D case-control pairs (n”=2,152) without existing genetic data. Adopting both standard statistical methods and the cutting-edge Mendelian randomization method for causal inference, we will leverage these exceptional resources and the substantial investment of time and effort by WHI/HPFS study investigators over the past two decades to investigate, in a most cost-efficient and timely manner, the effect of this novel and promising hormone – asprosin – for obesity and T2D development. We will be the first to investigate 1) the distribution of plasma asprosin levels in men and women, 2) the genetic variations affecting asprosin functions in diverse human populations, and 3) the potential causal relation between asprosin and obesity and T2D in human populations of diverse ethnicity including white or Caucasian American (CA), African American (AA), and Hispanic American (HA).

项目摘要 Asprosin，通过研究新生儿后代综合征（NP或Marfan 脂肪营养不良综合征），可能对肥胖和糖尿病具有治疗和诊断意义。编码Asprosin，FBN1的基因具有独特的极端3'突变，导致降血糖症状和低糖症少数患有稀有NP的患者的血浆胰岛素水平。最近证明了大量证据 asprosin在肝葡萄糖生产调节中的直接作用，以及在在小鼠模型中治疗肥胖和糖尿病。 asprosin对2型糖尿病（T2D）的直接影响人群中尚未调查人类的发病率。当前的申请旨在调查在两个大型和高质量的预期男女同伙。我们计划整合有关相关遗传变异，生化标记和国家女性健康计划（WHI）和男子的肥胖和T2D发病率的临床表型卫生专业人员后续研究（HPFS）。 WHI和HPF都是长期前瞻性队列由NIH资助，详细且高质量的饮食，生活方式，临床，生化和基因组数据，以及大量使用标准化协议的特征和验证的事件T2D案例始终在20年的后续行动中进行。所有事件T2D病例都有现有遗传数据和空腹血液样品（N1 = 2,615）与从同一WHI随机选择的对照数（N0 = 2,615）匹配使用相同的嵌套案例 - 控制设计。基因分型和验证分析将在另外1,076 T2D病例对照中进行对（N” = 2,152），没有现有遗传数据。同时采用标准统计方法和尖端 Mendelian随机化方法用于因果推断，我们将利用这些特殊资源和在过去的二十年中以最具成本效益和及时的方式调查这款小说和有前途的马的效果 - asprosin - 肥胖和T2D发展。我们将是第一个研究1）血浆asprosin水平的分布在男性和女性中，2）影响阿斯普罗斯蛋白在潜水人群中起作用的遗传变异，3）潜水员种族人口中的asprosin与肥胖与T2D之间的潜在因果关系包括白人或高加索美国人（CA），非裔美国人（AA）和西班牙裔美国人（HA）。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A network meta-analysis of association between cardiometabolic risk factors and COVID-19 outcome severity.

DOI：
10.1111/1753-0407.13445
发表时间：
2023-11
期刊：
Journal of diabetes
影响因子：
4.5
作者：
通讯作者：

Caudamins, a new subclass of protein hormones.

DOI：
10.1016/j.tem.2021.09.005
发表时间：
2021-12
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
0
作者：
Basu B;Jain M;Chopra AR
通讯作者：
Chopra AR

Relationship Between a Plant-Based Dietary Portfolio and Risk of Cardiovascular Disease: Findings From the Women's Health Initiative Prospective Cohort Study.

DOI：
10.1161/jaha.121.021515
发表时间：
2021-08-17
期刊：
Journal of the American Heart Association
影响因子：
5.4
作者：
Glenn AJ;Lo K;Jenkins DJA;Boucher BA;Hanley AJ;Kendall CWC;Manson JE;Vitolins MZ;Snetselaar LG;Liu S;Sievenpiper JL
通讯作者：
Sievenpiper JL

Asprosin-neutralizing antibodies as a treatment for metabolic syndrome.

DOI：
10.7554/elife.63784
发表时间：
2021-04-27
期刊：
eLife
影响因子：
7.7
作者：
Mishra I;Duerrschmid C;Ku Z;He Y;Xie W;Silva ES;Hoffman J;Xin W;Zhang N;Xu Y;An Z;Chopra AR
通讯作者：
Chopra AR

Added Sugar, Sugar-Sweetened Beverages, and Artificially Sweetened Beverages and Risk of Cardiovascular Disease: Findings from the Women's Health Initiative and a Network Meta-Analysis of Prospective Studies.

DOI：
10.3390/nu14204226
发表时间：
2022-10-11
期刊：
Nutrients
影响因子：
5.9
作者：
Yang B;Glenn AJ;Liu Q;Madsen T;Allison MA;Shikany JM;Manson JE;Chan KHK;Wu WC;Li J;Liu S;Lo K
通讯作者：
Lo K