Ectopic Lipid in Skeletal Muscle is Associated with Glucose Intolerance in Veterans with HIV
骨骼肌中的异位脂质与感染艾滋病毒的退伍军人的葡萄糖不耐受有关
基本信息
- 批准号:9885568
- 负责人:
- 金额:--
- 依托单位:
- 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:2020-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:ATP Synthesis PathwayAbdominal MusclesAdipocytesAdipose tissueAffectAgeAttentionBenignBioenergeticsBody WeightBody fatCD4/CD8 ratio procedureCardiovascular DiseasesCaringClinical assessmentsComplexContractsDataDefectDepositionDevelopmentDiabetes MellitusDiseaseEndocrinologyFatty acid glycerol estersFoundationsFutureGlucose IntoleranceGlucose TransporterGoalsHIVHIV InfectionsHIV SeronegativityHealthHealthcareHepaticImageImpairmentInfiltrationInflammationInsulin ResistanceInterdisciplinary StudyInterventionLinkLipidsLiverMedicalMetabolicMetabolic DiseasesMitochondriaModelingMuscleMuscle CellsMuscle MitochondriaNon-Insulin-Dependent Diabetes MellitusNonesterified Fatty AcidsObesityOrganOverweightPathogenesisPathologicPathologyPhenotypePlasmaPopulationProductionProviderRaceRegulationResearchResearch PersonnelRiskRisk FactorsRoleSiteSkeletal MuscleTestingTimeTissuesTriglyceridesUnited StatesVeteransX-Ray Computed Tomographyacylcarnitineantiretroviral therapyblood glucose regulationcardiometabolismcohortcomorbiditydemographicsdensitydiabetes riskdiabeticexperienceglucose metabolismglucose toleranceglucose uptakehealth administrationhigh riskimpaired glucose toleranceimprovedinsulin secretioninsulin sensitivityinsulin signalingmitochondrial dysfunctionmuscle physiologynon-diabeticnovelnutritionoxidationpatient populationpreventrecruitsexsuccess
项目摘要
The Department of Veterans Affairs is the largest provider of medical care to people with HIV in the United
States; in 2016 ~30,000 Veterans received treatment for HIV from the Veterans Health Administration (VHA).
Over the last several decades, the success of antiretroviral therapy (ART) treatment for HIV infection has
changed the demographics and phenotype of Veterans living with HIV. Although HIV+ Veterans are living longer,
78% of them are overweight or obese, and they have a two-fold greater risk of developing type 2 diabetes
compared to Veterans without HIV. While much of the research on HIV and metabolic disease has focused on
the interaction between obesity and the accumulation of ectopic fat in the liver, several recent studies highlight
the central role of ectopic fat in skeletal muscle in the pathogenesis of insulin resistance and diabetes. However,
this important phenomenon has received little attention in the context of HIV infection and the role of skeletal
muscle ectopic fat in the complex interaction between HIV and obesity remains unclear.
Defects in adipose tissue lipid storage and regulation are hallmark of both HIV infection and obesity, which leads
to a high degree of ectopic fat accumulation in tissues such as the liver and skeletal muscle. While several
studies have investigated ectopic liver fat as a risk factor for diabetes in HIV, our novel hypothesis is that impaired
glucose tolerance in Veterans with treated HIV and obesity is driven by disproportionately greater ectopic lipid
infiltration of skeletal muscle (the primary site of glucose uptake) promoting impaired myocyte bioenergetics and
glucose homeostasis (Fig.1). This is supported by our preliminary CT imaging, MRS imaging, and glucose
metabolism data that implicate skeletal muscle pathology in HIV associated glucose intolerance: 1) Our CT data
show ectopic fat infiltration in muscle is greater in HIV+ diabetics vs nondiabetics; 2) Our MRS data show higher
muscle triglyceride content is associated with a slower rate of ATP synthesis; 3) Our metabolic data show lower
plasma acylcarnitines (indicating impaired mitochondrial oxidation) correlates with insulin resistance in HIV.
In the proposed study, we aim to determine: a) whether the deposition of excess lipid in skeletal muscle in HIV+
Veterans is a phenomenon separate from hepatic fat deposition and a hallmark for T2DM in this population (Aim
1); b) whether skeletal muscle fat accumulates over time in nondiabetic overweight/obese Veterans and is
accompanied by reductions in muscle mitochondrial oxidative capacity, ATP production, and muscle force (Aim
2); and c) whether changes in skeletal muscle ectopic fat and mitochondrial oxidative capacity over time are
accompanied by reductions in insulin sensitivity and glucose tolerance (Aim 3).
To accomplish these aims, we will recruit two cohorts of HIV+ Veterans on long-term ART that will be matched
by sex, age, race, BMI and CD4/CD8 ratio. Group 1: 45 Veterans with HIV, obesity and type 2 diabetes; Group
2: 45 Veterans with HIV, obesity and no diabetes. Our study will: 1) determine the contribution of ectopic fat in
skeletal muscle vs liver to developing glucose intolerance in HIV; 2) identify temporal changes and determine
relationships in skeletal muscle ectopic fat infiltration and impairments in mitochondrial function in HIV; 3) identify
temporal changes and clarify relationships between skeletal muscle ectopic fat, liver ectopic fat, mitochondrial
function, and glucose tolerance in HIV; 4) establish a foundation for future studies targeting ectopic fat deposition
to improve metabolic health; and 5) inform our understanding of lipid pathology and the development of diabetes
in treated HIV, yielding opportunities for interventions to advance the healthcare of our Veterans.
退伍军人事务部是美国最大的艾滋病毒感染者医疗保健提供者
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John Koethe其他文献
John Koethe的其他文献
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{{ truncateString('John Koethe', 18)}}的其他基金
Cardiometabolic Consequences And Pathway Of Weight Gain Associated With Dolutegravir-Based Antiretroviral Therapy In Haiti. A Collaborative Study Between GHESKIO And CCASAnet
海地基于多替拉韦的抗逆转录病毒治疗相关的心脏代谢后果和体重增加途径。
- 批准号:
10750906 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Ectopic Lipid in Skeletal Muscle is Associated with Glucose Intolerance in Veterans with HIV
骨骼肌中的异位脂质与感染艾滋病毒的退伍军人的葡萄糖不耐受有关
- 批准号:
10417013 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Ectopic Lipid in Skeletal Muscle is Associated with Glucose Intolerance in Veterans with HIV
骨骼肌中的异位脂质与感染艾滋病毒的退伍军人的葡萄糖不耐受有关
- 批准号:
10651630 - 财政年份:2020
- 资助金额:
-- - 项目类别:
The Role of Adipose-Resident T Cells in HIV-Associated Glucose Intolerance
脂肪驻留 T 细胞在 HIV 相关葡萄糖不耐受中的作用
- 批准号:
9429306 - 财政年份:2017
- 资助金额:
-- - 项目类别:
The Role of Adipose-Resident T Cells in HIV-Associated Glucose Intolerance
脂肪驻留 T 细胞在 HIV 相关葡萄糖不耐受中的作用
- 批准号:
10093023 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Innate and Adaptive Immunity in HIV-associated Impaired Glucose Tolerance and Diabetes
HIV 相关糖耐量受损和糖尿病中的先天免疫和适应性免疫
- 批准号:
9260968 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Tennessee Center for AIDS Research (TN-CFAR)
田纳西州艾滋病研究中心 (TN-CFAR)
- 批准号:
10617275 - 财政年份:2015
- 资助金额:
-- - 项目类别:
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