TY - JOUR
T1 - Lipid overload and overflow
T2 - Metabolic trauma and the metabolic syndrome
AU - Unger, Roger H
N1 - Funding Information:
I thank Susan Kennedy and Christie Fisher for superb secretarial work, Kay McCorkle for outstanding illustrations, and Daniel Foster, Michael S. Brown and Christopher B. Newgard for critical reviews. This work was supported by National Institutes of Health Grants DK02700 and DK58308, Department of Veterans Affairs Merit Review, and the Jensen Diabetes Research Foundation.
PY - 2003/11
Y1 - 2003/11
N2 - Approximately two-thirds of the US population are overweight, which means that insulin resistance is probably the most common metabolic abnormality in the USA. I propose three novel concepts concerning the causes and consequences of insulin resistance that challenge current thinking. First, there is the evidence that resistance to insulin-stimulated glucose metabolism is not a primary event in obesity, but is secondary to lipid accumulation resulting from full responsiveness to insulin-stimulated lipogenic activity. Second, resistance to insulin-stimulated glucose metabolism, now considered detrimental to health, might be a protective mechanism that reduces lipid-induced damage to tissue by excluding glucose from cells, thus decreasing glucose-derived lipogenesis. Third, I suggest that lipid-induced insulin resistance and the accompanying metabolic syndrome are secondary to leptin resistance, resulting in breakdown in the normal partitioning of surplus lipids in the adipocyte compartment.
AB - Approximately two-thirds of the US population are overweight, which means that insulin resistance is probably the most common metabolic abnormality in the USA. I propose three novel concepts concerning the causes and consequences of insulin resistance that challenge current thinking. First, there is the evidence that resistance to insulin-stimulated glucose metabolism is not a primary event in obesity, but is secondary to lipid accumulation resulting from full responsiveness to insulin-stimulated lipogenic activity. Second, resistance to insulin-stimulated glucose metabolism, now considered detrimental to health, might be a protective mechanism that reduces lipid-induced damage to tissue by excluding glucose from cells, thus decreasing glucose-derived lipogenesis. Third, I suggest that lipid-induced insulin resistance and the accompanying metabolic syndrome are secondary to leptin resistance, resulting in breakdown in the normal partitioning of surplus lipids in the adipocyte compartment.
UR - http://www.scopus.com/inward/record.url?scp=0242696221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242696221&partnerID=8YFLogxK
U2 - 10.1016/j.tem.2003.09.008
DO - 10.1016/j.tem.2003.09.008
M3 - Article
C2 - 14580758
AN - SCOPUS:0242696221
SN - 1043-2760
VL - 14
SP - 398
EP - 403
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 9
ER -