TY - JOUR
T1 - Lipoapoptosis
T2 - Its mechanism and its diseases
AU - Unger, Roger H
AU - Orci, Lelio
N1 - Funding Information:
The authors thank Susan Kennedy for superb secretarial services and Kay McCorkle for technical support. We acknowledge the grant support of the Department of Veterans Affairs Institutional Support (SMI 821-109), The National Institutes of Health (DK02700-37), and The National Institutes of Health/Juvenile Diabetes Foundation Diabetes Interdisciplinary Research Program.
PY - 2002/12/30
Y1 - 2002/12/30
N2 - The balance between cell division and cell death determines the cell population of an organ. When cell death exceeds cell replacement in an organ, a functional deficit is created. A metabolic cause of programmed cell death, lipoapoptosis, has recently been identified to occur in obesity and aging. If nonadipose tissues are exposed to an excess of long-chain fatty acids, unless leptin action increases their oxidation sufficiently, unoxidized fatty acids enter nonoxidative pathways. While initially they are sequestered as harmless neutral fat, ultimately some will enter more toxic pathways. One of these, the de novo ceramide pathway, has been implicated in the lipoapoptosis of β-cells and myocardiocytes of congenitally obese rats in which leptin action is defective. Here we review the mechanisms of lipoapoptosis and the diseases that result from this cause of a diminishing cell population of these organs. We suggest that some of the components of the metabolic syndrome of obese humans and the sarcopenia of aging may be result of failure of leptin liporegulation to prevent lipid overload of lean body mass and lipoapoptosis in certain organ systems.
AB - The balance between cell division and cell death determines the cell population of an organ. When cell death exceeds cell replacement in an organ, a functional deficit is created. A metabolic cause of programmed cell death, lipoapoptosis, has recently been identified to occur in obesity and aging. If nonadipose tissues are exposed to an excess of long-chain fatty acids, unless leptin action increases their oxidation sufficiently, unoxidized fatty acids enter nonoxidative pathways. While initially they are sequestered as harmless neutral fat, ultimately some will enter more toxic pathways. One of these, the de novo ceramide pathway, has been implicated in the lipoapoptosis of β-cells and myocardiocytes of congenitally obese rats in which leptin action is defective. Here we review the mechanisms of lipoapoptosis and the diseases that result from this cause of a diminishing cell population of these organs. We suggest that some of the components of the metabolic syndrome of obese humans and the sarcopenia of aging may be result of failure of leptin liporegulation to prevent lipid overload of lean body mass and lipoapoptosis in certain organ systems.
KW - Lipoapoptosis
KW - Obesity
KW - β Cell
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U2 - 10.1016/S1388-1981(02)00342-6
DO - 10.1016/S1388-1981(02)00342-6
M3 - Review article
C2 - 12531555
AN - SCOPUS:0037203345
SN - 1388-1981
VL - 1585
SP - 202
EP - 212
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 2-3
ER -