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Metabolic Flexibility in the Postprandial Period Is Attenuated in Healthy Aging
Metabolic Flexibility in the Postprandial Period Is Attenuated in Healthy Aging
Metabolic Flexibility in the Postprandial Period Is Attenuated in Healthy Aging

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211152035
ISBN  
9798384447849
DDC  
612
저자명  
Osmond, Adam D.
서명/저자  
Metabolic Flexibility in the Postprandial Period Is Attenuated in Healthy Aging
발행사항  
[Sl] : University of California, Berkeley, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
240 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
주기사항  
Advisor: Brooks, George A.
학위논문주기  
Thesis (Ph.D.)--University of California, Berkeley, 2024.
초록/해제  
요약Aging-related decrements in metabolic flexibility have been reported during supraphysiological conditions, but responses to physiological perturbations are less studied. The purpose of this research was to assess metabolic flexibility by determining changes in the rates of whole-body lipolysis, fatty acid (FA) oxidation, carbohydrate (CHO) oxidation, and FA reesterification in the postprandial period. Further, we sought to examine how lactate controls energy substrate partitioning in the postprandial period. After a 12-hr overnight fast, 15 young (21-35 yr; 7 men and 8 women) and 14 older (60-80 yr; 7 men and 7 women) participants had the forearm vein catheterized for primed, continuous infusion of [1,1,2,3,3-2H]glycerol. A contralateral warmed hand vein was catheterized for arterialized blood sampling. Indirect calorimetry was performed simultaneously to determine total FA and CHO oxidation rates (Rox). Total FA reesterification rates (Rs) were estimated from tracer-measured lipolytic and FA oxidation rates. After a 90-min equilibration period, participants underwent a 120-min, 75-g oral glucose tolerance test (OGTT).In young participants, glycerol rate of appearance (Ra) (an index of lipolysis) decreased from baseline 5 min post-challenge (p = 0.03), remained steady until 15 min, decreased until 30 min (p 0.001), and then continuously declined until the end of observation at 120 min (P 0.001). In older participants, Ra decreased 30 min post-challenge (p = 0.002) and then remained low until 120 min (p ≤ 0.003). There were no differences in glycerol Ra between groups at any time (p ≥ 0.14). Blood lactate concentrations were inversely correlated with glycerol Ra in both groups, but the correlation was higher in older participants (r = -0.93 vs. r = -0.71).At 60 min post-challenge, FA Rox decreased from baseline in both groups (p 0.001), but FA Rox was higher in older participants (p = 0.04). In young participants, CHO Rox increased 5 min post-challenge (p = 0.02) and then remained elevated until 120 min (p ≤ 0.01). In older participants, CHO Rox increased 30 min post-challenge (p = 0.02) and then continuously rose until 120 min (p 0.001). In both groups, FA Rs decreased between 5-30 min post-challenge (p ≤ 0.002) and then increased, but FA Rs was lower in older participants at 60 min (p = 0.02) and 90 min (p = 0.03). The AUC for FA Rox was greater than that for FA Rs in older (p = 0.008), but not young participants (p = 0.34). Blood lactate concentrations and lactate oxidation rates were inversely correlated with FA Rox in both groups, but the correlations were higher in older participants (r ≥ -0.83 vs. r ≤ 0.73).In young participants, plasma insulin concentrations increased from baseline 5 min post-challenge (p = 0.01), continuously rose until 30 min (p = 0.001), and then remained elevated until 120 min (p 0.001). In older participants, [Insulin] increased 15 min post-challenge (p 0.001) and then remained elevated until 120 min (p 0.001). Further, [Insulin] was higher in young participants at 5 min (p = 0.05) and 30 min (p = 0.01) post-challenge. Plasma [Insulin] was inversely correlated with glycerol Ra in both groups, but the correlation was higher in older participants (r = -0.98 vs. r = -0.78). Further, the correlations between [Lactate], [Insulin], glycerol Ra, and FA Rox were more significant in older participants (p ≤ 0.02 vs. p ≥ 0.04).Our results indicate that metabolic flexibility to oral glucose consumption is delayed in "healthy" aging. Specifically, we report the following: (1) the suppression of lipolysis was delayed, (2) the fall in FA oxidation and rise in CHO oxidation rates were delayed; (3) the suppression of FA oxidation was attenuated such that FA oxidation was favored over CHO oxidation and FA reesterification, and (4) lactate is involved in the suppression of lipid metabolism in aging.
일반주제명  
Physiology
일반주제명  
Aging
일반주제명  
Biology
키워드  
Fatty acid
키워드  
Lactate concentrations
키워드  
Lipolysis
키워드  
Metabolic flexibility
키워드  
Oral glucose
키워드  
Substrate utilization
기타저자  
University of California, Berkeley Integrative Biology
기본자료저록  
Dissertations Abstracts International. 86-03B.
전자적 위치 및 접속  
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■1001  ▼aOsmond,  Adam  D.
■24510▼aMetabolic  Flexibility  in  the  Postprandial  Period  Is  Attenuated  in  Healthy  Aging
■260    ▼a[Sl]▼bUniversity  of  California,  Berkeley▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a240  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-03,  Section:  B.
■500    ▼aAdvisor:  Brooks,  George  A.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  Berkeley,  2024.
■520    ▼aAging-related  decrements  in  metabolic  flexibility  have  been  reported  during  supraphysiological  conditions,  but  responses  to  physiological  perturbations  are  less  studied.  The  purpose  of  this  research  was  to  assess  metabolic  flexibility  by  determining  changes  in  the  rates  of  whole-body  lipolysis,  fatty  acid  (FA)  oxidation,  carbohydrate  (CHO)  oxidation,  and  FA  reesterification  in  the  postprandial  period.  Further,  we  sought  to  examine  how  lactate  controls  energy  substrate  partitioning  in  the  postprandial  period.  After  a  12-hr  overnight  fast,  15  young  (21-35  yr;  7  men  and  8  women)  and  14  older  (60-80  yr;  7  men  and  7  women)  participants  had  the  forearm  vein  catheterized  for  primed,  continuous  infusion  of  [1,1,2,3,3-2H]glycerol.  A  contralateral  warmed  hand  vein  was  catheterized  for  arterialized  blood  sampling.  Indirect  calorimetry  was  performed  simultaneously  to  determine  total  FA  and  CHO  oxidation  rates  (Rox).  Total  FA  reesterification  rates  (Rs)  were  estimated  from  tracer-measured  lipolytic  and  FA  oxidation  rates.  After  a  90-min  equilibration  period,  participants  underwent  a  120-min,  75-g  oral  glucose  tolerance  test  (OGTT).In  young  participants,  glycerol  rate  of  appearance  (Ra)  (an  index  of  lipolysis)  decreased  from  baseline  5  min  post-challenge  (p  =  0.03),  remained  steady  until  15  min,  decreased  until  30  min  (p    0.001),  and  then  continuously  declined  until  the  end  of  observation  at  120  min  (P    0.001).  In  older  participants,  Ra  decreased  30  min  post-challenge  (p  =  0.002)  and  then  remained  low  until  120  min  (p  ≤  0.003).  There  were  no  differences  in  glycerol  Ra  between  groups  at  any  time  (p  ≥  0.14).  Blood  lactate  concentrations  were  inversely  correlated  with  glycerol  Ra  in  both  groups,  but  the  correlation  was  higher  in  older  participants  (r  =  -0.93  vs.  r  =  -0.71).At  60  min  post-challenge,  FA  Rox  decreased  from  baseline  in  both  groups  (p    0.001),  but  FA  Rox  was  higher  in  older  participants  (p  =  0.04).  In  young  participants,  CHO  Rox  increased  5  min  post-challenge  (p  =  0.02)  and  then  remained  elevated  until  120  min  (p  ≤  0.01).  In  older  participants,  CHO  Rox  increased  30  min  post-challenge  (p  =  0.02)  and  then  continuously  rose  until  120  min  (p    0.001).  In  both  groups,  FA  Rs  decreased  between  5-30  min  post-challenge  (p  ≤  0.002)  and  then  increased,  but  FA  Rs  was  lower  in  older  participants  at  60  min  (p  =  0.02)  and  90  min  (p  =  0.03).  The  AUC  for  FA  Rox  was  greater  than  that  for  FA  Rs  in  older  (p  =  0.008),  but  not  young  participants  (p  =  0.34).  Blood  lactate  concentrations  and  lactate  oxidation  rates  were  inversely  correlated  with  FA  Rox  in  both  groups,  but  the  correlations  were  higher  in  older  participants  (r  ≥  -0.83  vs.  r  ≤  0.73).In  young  participants,  plasma  insulin  concentrations  increased  from  baseline  5  min  post-challenge  (p  =  0.01),  continuously  rose  until  30  min  (p  =  0.001),  and  then  remained  elevated  until  120  min  (p    0.001).  In  older  participants,  [Insulin]  increased  15  min  post-challenge  (p    0.001)  and  then  remained  elevated  until  120  min  (p    0.001).  Further,  [Insulin]  was  higher  in  young  participants  at  5  min  (p  =  0.05)  and  30  min  (p  =  0.01)  post-challenge.  Plasma  [Insulin]  was  inversely  correlated  with  glycerol  Ra  in  both  groups,  but  the  correlation  was  higher  in  older  participants  (r  =  -0.98  vs.  r  =  -0.78).  Further,  the  correlations  between  [Lactate],  [Insulin],  glycerol  Ra,  and  FA  Rox  were  more  significant  in  older  participants  (p  ≤  0.02  vs.  p  ≥  0.04).Our  results  indicate  that  metabolic  flexibility  to  oral  glucose  consumption  is  delayed  in  "healthy"  aging.  Specifically,  we  report  the  following:  (1)  the  suppression  of  lipolysis  was  delayed,  (2)  the  fall  in  FA  oxidation  and  rise  in  CHO  oxidation  rates  were  delayed;  (3)  the  suppression  of  FA  oxidation  was  attenuated  such  that  FA  oxidation  was  favored  over  CHO  oxidation  and  FA  reesterification,  and  (4)  lactate  is  involved  in  the  suppression  of  lipid  metabolism  in  aging.
■590    ▼aSchool  code:  0028.
■650  4▼aPhysiology
■650  4▼aAging
■650  4▼aBiology
■653    ▼aFatty  acid
■653    ▼aLactate  concentrations
■653    ▼aLipolysis
■653    ▼aMetabolic  flexibility
■653    ▼aOral  glucose
■653    ▼aSubstrate  utilization
■690    ▼a0719
■690    ▼a0493
■690    ▼a0306
■71020▼aUniversity  of  California,  Berkeley▼bIntegrative  Biology.
■7730  ▼tDissertations  Abstracts  International▼g86-03B.
■790    ▼a0028
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162630▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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