PMID- 26967715
OWN - NLM
STAT- MEDLINE
DCOM- 20161226
LR  - 20210607
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 247
DP  - 2016 Apr
TI  - Imbalanced insulin action in chronic over nutrition: Clinical harm, molecular 
      mechanisms, and a way forward.
PG  - 225-82
LID - S0021-9150(16)30048-X [pii]
LID - 10.1016/j.atherosclerosis.2016.02.004 [doi]
AB  - The growing worldwide prevalence of overnutrition and underexertion threatens the 
      gains that we have made against atherosclerotic cardiovascular disease and other 
      maladies. Chronic overnutrition causes the atherometabolic syndrome, which is a 
      cluster of seemingly unrelated health problems characterized by increased 
      abdominal girth and body-mass index, high fasting and postprandial concentrations 
      of cholesterol- and triglyceride-rich apoB-lipoproteins (C-TRLs), low plasma HDL 
      levels, impaired regulation of plasma glucose concentrations, hypertension, and a 
      significant risk of developing overt type 2 diabetes mellitus (T2DM). In 
      addition, individuals with this syndrome exhibit fatty liver, hypercoagulability, 
      sympathetic overactivity, a gradually rising set-point for body adiposity, a 
      substantially increased risk of atherosclerotic cardiovascular morbidity and 
      mortality, and--crucially--hyperinsulinemia. Many lines of evidence indicate that 
      each component of the atherometabolic syndrome arises, or is worsened by, 
      pathway-selective insulin resistance and responsiveness (SEIRR). Individuals with 
      SEIRR require compensatory hyperinsulinemia to control plasma glucose levels. The 
      result is overdrive of those pathways that remain insulin-responsive, 
      particularly ERK activation and hepatic de-novo lipogenesis (DNL), while 
      carbohydrate regulation deteriorates. The effects are easily summarized: if 
      hyperinsulinemia does something bad in a tissue or organ, that effect remains 
      responsive in the atherometabolic syndrome and T2DM; and if hyperinsulinemia 
      might do something good, that effect becomes resistant. It is a deadly imbalance 
      in insulin action. From the standpoint of human health, it is the worst possible 
      combination of effects. In this review, we discuss the origins of the 
      atherometabolic syndrome in our historically unprecedented environment that only 
      recently has become full of poorly satiating calories and incessant enticements 
      to sit. Data are examined that indicate the magnitude of daily caloric imbalance 
      that causes obesity. We also cover key aspects of healthy, balanced insulin 
      action in liver, endothelium, brain, and elsewhere. Recent insights into the 
      molecular basis and pathophysiologic harm from SEIRR in these organs are 
      discussed. Importantly, a newly discovered oxide transport chain functions as the 
      master regulator of the balance amongst different limbs of the insulin signaling 
      cascade. This oxide transport chain--abbreviated 'NSAPP' after its five major 
      proteins--fails to function properly during chronic overnutrition, resulting in 
      this harmful pattern of SEIRR. We also review the origins of widespread, chronic 
      overnutrition. Despite its apparent complexity, one factor stands out. A 
      sophisticated junk food industry, aided by subsidies from willing governments, 
      has devoted years of careful effort to promote overeating through the creation of 
      a new class of food and drink that is low- or no-cost to the consumer, 
      convenient, savory, calorically dense, yet weakly satiating. It is past time for 
      the rest of us to overcome these foes of good health and solve this man-made 
      epidemic.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Williams, Kevin Jon
AU  - Williams KJ
AD  - Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, 
      Temple University School of Medicine, Philadelphia, PA, USA; Department of 
      Molecular and Clinical Medicine, Sahlgrenska Academy of the University of 
      Gothenburg, Gothenburg, Sweden. Electronic address: kjwilliams@temple.edu.
FAU - Wu, Xiangdong
AU  - Wu X
AD  - Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, 
      Temple University School of Medicine, Philadelphia, PA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160213
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Biomarkers)
RN  - 0 (Insulin)
SB  - IM
EIN - Atherosclerosis. 2021 Jul;328:60-61. PMID: 34098464
MH  - Animals
MH  - Atherosclerosis/blood/epidemiology/physiopathology
MH  - Biomarkers/blood
MH  - Diabetes Mellitus, Type 2/blood/epidemiology/physiopathology
MH  - Energy Intake
MH  - *Energy Metabolism
MH  - Fast Foods/adverse effects
MH  - Humans
MH  - Insulin/*blood
MH  - Metabolic Syndrome/blood/epidemiology/physiopathology
MH  - *Nutritional Status
MH  - Nutritive Value
MH  - Obesity, Abdominal/blood/epidemiology/physiopathology
MH  - Overnutrition/*blood/epidemiology/physiopathology
MH  - Risk Assessment
MH  - Risk Factors
MH  - Sedentary Behavior
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Chronic overnutrition
OT  - Clinical harm
OT  - Imbalanced insulin action
OT  - Molecular mechanisms
OT  - Signaling
EDAT- 2016/03/12 06:00
MHDA- 2016/12/27 06:00
CRDT- 2016/03/12 06:00
PHST- 2015/08/26 00:00 [received]
PHST- 2015/12/31 00:00 [revised]
PHST- 2016/02/02 00:00 [accepted]
PHST- 2016/03/12 06:00 [entrez]
PHST- 2016/03/12 06:00 [pubmed]
PHST- 2016/12/27 06:00 [medline]
AID - S0021-9150(16)30048-X [pii]
AID - 10.1016/j.atherosclerosis.2016.02.004 [doi]
PST - ppublish
SO  - Atherosclerosis. 2016 Apr;247:225-82. doi: 10.1016/j.atherosclerosis.2016.02.004. 
      Epub 2016 Feb 13.