PMID- 26355033
OWN - NLM
STAT- MEDLINE
DCOM- 20160613
LR  - 20230411
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 7
IP  - 304
DP  - 2015 Sep 9
TI  - Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, 
      and insulin resistance in healthy men.
PG  - 304re7
LID - 10.1126/scitranslmed.aac4765 [doi]
AB  - Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, 
      hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known 
      as the metabolic or insulin resistance syndrome. How obesity promotes insulin 
      resistance remains incompletely understood. Plasma concentrations of free fatty 
      acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and 
      oxidative stress are all elevated in obesity and have been shown to induce 
      insulin resistance. However, they may be late events that only develop after 
      chronic excessive nutrient intake. The nature of the initial event that produces 
      insulin resistance at the beginning of excess caloric intake and weight gain 
      remains unknown. We show that feeding healthy men with ~6000 kcal/day of the 
      common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 
      week produced a rapid weight gain of 3.5 kg and the rapid onset (after 2 to 3 
      days) of systemic and adipose tissue insulin resistance and oxidative stress but 
      no inflammatory or ER stress. In adipose tissue, the oxidative stress resulted in 
      extensive oxidation and carbonylation of numerous proteins, including 
      carbonylation of GLUT4 near the glucose transport channel, which likely resulted 
      in loss of GLUT4 activity. These results suggest that the initial event caused by 
      overnutrition may be oxidative stress, which produces insulin resistance, at 
      least in part, via carbonylation and oxidation-induced inactivation of GLUT4.
CI  - Copyright (c) 2015, American Association for the Advancement of Science.
FAU - Boden, Guenther
AU  - Boden G
AD  - Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Unit, 
      Temple University School of Medicine, Philadelphia, PA 19140, USA. 
      bodengh@tuhs.temple.edu smerali@temple.edu.
FAU - Homko, Carol
AU  - Homko C
AD  - Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Unit, 
      Temple University School of Medicine, Philadelphia, PA 19140, USA.
FAU - Barrero, Carlos A
AU  - Barrero CA
AD  - Department of Pharmaceutical Sciences and Moulder Center for Drug Discovery, 
      Proteomics/Metabolomics Facility, Temple University School of Pharmacy, 
      Philadelphia, PA 19140, USA.
FAU - Stein, T Peter
AU  - Stein TP
AD  - Department of Surgery, School of Osteopathic Medicine, Rowan University, 
      Stratford, NJ 08084, USA.
FAU - Chen, Xinhua
AU  - Chen X
AD  - Department of Obstetrics and Gynecology, School of Osteopathic Medicine, Rowan 
      University, Stratford, NJ 08084, USA.
FAU - Cheung, Peter
AU  - Cheung P
AD  - Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Unit, 
      Temple University School of Medicine, Philadelphia, PA 19140, USA.
FAU - Fecchio, Chiara
AU  - Fecchio C
AD  - Department of Pharmaceutical Sciences and Moulder Center for Drug Discovery, 
      Proteomics/Metabolomics Facility, Temple University School of Pharmacy, 
      Philadelphia, PA 19140, USA.
FAU - Koller, Sarah
AU  - Koller S
AD  - Department of Surgery, Temple University School of Medicine, Philadelphia, PA 
      19140, USA.
FAU - Merali, Salim
AU  - Merali S
AD  - Department of Pharmaceutical Sciences and Moulder Center for Drug Discovery, 
      Proteomics/Metabolomics Facility, Temple University School of Pharmacy, 
      Philadelphia, PA 19140, USA. bodengh@tuhs.temple.edu smerali@temple.edu.
LA  - eng
GR  - R01 DK090588/DK/NIDDK NIH HHS/United States
GR  - R01-DK090588/DK/NIDDK NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (SLC2A4 protein, human)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - *Energy Intake
MH  - Glucose Transporter Type 4/*metabolism
MH  - *Health
MH  - Humans
MH  - *Insulin Resistance
MH  - Male
MH  - Middle Aged
MH  - Models, Molecular
MH  - Overnutrition/metabolism/pathology
MH  - Oxidation-Reduction
MH  - *Oxidative Stress
MH  - *Protein Carbonylation
MH  - Protein Processing, Post-Translational
MH  - Reactive Oxygen Species/metabolism
PMC - PMC5600191
MID - NIHMS750570
EDAT- 2015/09/12 06:00
MHDA- 2016/06/14 06:00
PMCR- 2017/09/15
CRDT- 2015/09/11 06:00
PHST- 2015/09/11 06:00 [entrez]
PHST- 2015/09/12 06:00 [pubmed]
PHST- 2016/06/14 06:00 [medline]
PHST- 2017/09/15 00:00 [pmc-release]
AID - 7/304/304re7 [pii]
AID - 10.1126/scitranslmed.aac4765 [doi]
PST - ppublish
SO  - Sci Transl Med. 2015 Sep 9;7(304):304re7. doi: 10.1126/scitranslmed.aac4765.