Mechanisms of Metabolic Regulation by Dietary Methionine Restriction
Mechanisms of Metabolic Regulation by Dietary Methionine Restriction
批准号:
9896807
负责人:
Thomas W Gettys
金额:
$37.0万
依托单位国家:
美国
项目类别:
财政年份:
2012
资助国家:
美国
项目状态:
已结题
起止时间:
2012-07-01 至 2022-03-31
关键词:
AddressAdipocytesAdipose tissueAffectAnimal ModelBackBindingBiochemicalBiological MarkersBrainBrown FatCell Culture TechniquesCell LineChronicCollaborationsConsumptionCoupledCyclic AMP-Responsive DNA-Binding ProteinCysteineDataDepositionDevelopmentDiabetes MellitusDietDiet ModificationDiseaseEndoplasmic ReticulumEnergy MetabolismEssential Amino AcidsEventFGF21 geneFatty acid glycerol estersGene ExpressionGenetic TranscriptionGlutathioneGoalsHealthHeart DiseasesHepaticHepatocyteIn VitroIndividualInsulin ResistanceLettersLinkLiverMediatingMetabolicMetabolic DiseasesMetabolic hormoneMetabolic syndromeMethionineMouse StrainsMusObesityPeripheralPhenotypePhosphotransferasesPhysiologicalPlayProteinsPublishingRegulationResearchRoleSeriesSignal TransductionStrokeSystemTestingThermogenesisTissuesTransactivationTranslatingTriglyceridesWorkbasecomorbiditydetection of nutrientdietary restrictioneffective interventioneffective therapyenergy balanceexperimental studyimprovedin vivoinsulin sensitivityknock-downlipid disorderlipid metabolismliquid chromatography mass spectrometryloss of functionmetabolic phenotypepreclinical studyprogramspromoterrecruitresponsetranscription factor
中文摘要
膳食蛋氨酸限制(MR)产生一系列高度整合的生化和
英文摘要
Dietary methionine restriction (MR) produces a highly integrated series of biochemical and
physiological responses that reduce adiposity, improve biomarkers of metabolic health and
enhance insulin sensitivity. Our data make a compelling case that dietary MR acts through both
centrally-mediated effects on energy balance, and direct effects on peripheral tissues that
remodel white adipose tissue, activate thermogenesis in brown adipose tissue, and enhance
insulin sensitivity. We hypothesize that sensing of dietary MR is coupled to these responses
through hepatic sensing of reduced methionine through a glutathione-dependent mechanism
that activates CREBH and the eIF2 kinase, PERK. The activation of CREBH and PERK results
in activation eIF2α- and NRF2-dependent transcriptional programs that increase hepatic
expression and release of FGF21. We hypothesize that the increase in FGF21 acts through
direct and centrally-mediated mechanisms to activate thermogenesis, increase energy
expenditure, reduce fat deposition, and enhance overall insulin sensitivity. We will use a
combination of in vivo metabolic phenotyping and ex vivo biochemical analysis with loss of
function animal models to examine the role of essential amino acid sensing in the respective
responses to dietary MR. The goal of this work is to identify the nutrient sensing and signaling
systems which detect the restriction of methionine and translate this dietary modification into a
highly integrated and beneficial set of physiological responses.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.isci.2021.102470
发表时间:
2021-05-21
期刊:
iScience
影响因子:
5.8
作者:
[Fang H, Stone KP, Forney LA, Sims LC, Gutierrez GC, Ghosh S, Gettys TW]
通讯作者:
Gettys TW
Mentoring Obesity and Diabetes Research in Louisiana
-
批准号:9322390
-
项目类别:
-
资助金额:$111.0万
-
财政年份:2016
-
负责人:Thomas W Gettys
-
依托单位:
Mentoring Obesity and Diabetes Research in Louisiana
-
批准号:9320355
-
项目类别:
-
资助金额:$20.98万
-
财政年份:2016
-
负责人:Thomas W Gettys
-
依托单位:
Mentoring Obesity and Diabetes Research in Louisiana
-
批准号:9978071
-
项目类别:
-
资助金额:$111.0万
-
财政年份:2016
-
负责人:Thomas W Gettys
-
依托单位:
Pilot Feasibility Core
-
批准号:9978079
-
项目类别:
-
资助金额:$40.85万
-
财政年份:2016
-
负责人:Thomas W Gettys
-
依托单位:
Administrative Core
-
批准号:9978090
-
项目类别:
-
资助金额:$23.47万
-
财政年份:2016
-
负责人:Thomas W Gettys
-
依托单位:
MECHANISMS OF METABOLIC REGULATION BY DIETARY METHIONINE RESTRICTION
-
批准号:8686834
-
项目类别:
-
资助金额:$32.19万
-
财政年份:2012
-
负责人:Thomas W Gettys
-
依托单位:
MECHANISMS OF METABOLIC REGULATION BY DIETARY METHIONINE RESTRICTION
-
批准号:8502489
-
项目类别:
-
资助金额:$31.06万
-
财政年份:2012
-
负责人:Thomas W Gettys
-
依托单位:
MECHANISMS OF METABOLIC REGULATION BY DIETARY METHIONINE RESTRICTION
-
批准号:8874213
-
项目类别:
-
资助金额:$32.19万
-
财政年份:2012
-
负责人:Thomas W Gettys
-
依托单位:
MECHANISMS OF METABOLIC REGULATION BY DIETARY METHIONINE RESTRICTION
-
批准号:8350430
-
项目类别:
-
资助金额:$32.19万
-
财政年份:2012
-
负责人:Thomas W Gettys
-
依托单位:
MENTORING OBESITY AND DIABETES RESEARCH IN LOUISIANA
-
批准号:8360767
-
项目类别:
-
资助金额:$222.0万
-
财政年份:2011
-
负责人:Thomas W Gettys
-
依托单位:
LOUISIANA COBRE: OBESITY & DIABETES RES: ADMINISTRATIVE CORE
-
批准号:8167948
-
项目类别:
-
资助金额:$35.08万
-
财政年份:2010
-
负责人:Thomas W Gettys
-
依托单位:
LOUISIANA COBRE: OBESITY & DIABETES RES: ADMINISTRATIVE CORE
-
批准号:7959982
-
项目类别:
-
资助金额:$32.35万
-
财政年份:2009
-
负责人:Thomas W Gettys
-
依托单位:
LOUISIANA COBRE: OBESITY & DIABETES RES: ADMINISTRATIVE CORE
-
批准号:7720509
-
项目类别:
-
资助金额:$31.0万
-
财政年份:2008
-
负责人:Thomas W Gettys
-
依托单位:
Regulation of SNS-dependent Remodeling of Adipose Tissue by a Novel Form of PGC-1
-
批准号:7340513
-
项目类别:
-
资助金额:$29.53万
-
财政年份:2007
-
负责人:Thomas W Gettys
-
依托单位:
Regulation of SNS-dependent Remodeling of Adipose Tissue by a Novel Form of PGC-1
-
批准号:7566005
-
项目类别:
-
资助金额:$29.53万
-
财政年份:2007
-
负责人:Thomas W Gettys
-
依托单位:
LOUISIANA COBRE: OBESITY & DIABETES RES: ADMINISTRATIVE CORE
-
批准号:7610778
-
项目类别:
-
资助金额:$30.75万
-
财政年份:2007
-
负责人:Thomas W Gettys
-
依托单位:
Regulation of SNS-dependent Remodeling of Adipose Tissue by a Novel Form of PGC-1
-
批准号:7212687
-
项目类别:
-
资助金额:$30.14万
-
财政年份:2007
-
负责人:Thomas W Gettys
-
依托单位:
Mentoring Obesity and Diabetes Research in Louisiana
-
批准号:8901222
-
项目类别:
-
资助金额:$222.0万
-
财政年份:2006
-
负责人:Thomas W Gettys
-
依托单位:
Mentoring Obesity and Diabetes Research in Louisiana
-
批准号:7893559
-
项目类别:
-
资助金额:$148.6万
-
财政年份:2006
-
负责人:Thomas W Gettys
-
依托单位:
Mentoring Obesity and Diabetes Research in Louisiana
-
批准号:8528633
-
项目类别:
-
资助金额:$214.23万
-
财政年份:2006
-
负责人:Thomas W Gettys
-
依托单位:
国内基金
海外基金
支链氨基酸代谢紊乱调控“Adipocytes - Macrophages Crosstalk”诱发2型糖尿病脂肪组织功能和结构障碍的作用及机制
-
批准号:81970721
-
项目类别:面上项目
-
资助金额:55.0万元
-
批准年份:2019
-
负责人:陶凌
-
依托单位: