Lipoapoptosis: its mechanism and its diseases.
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 beta-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.
Unger
Roger H
RH
Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8854, USA. Roger.Unger@UTSouthwestern.edu
Orci
Lelio
L
D000217:Acyltransferases / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008060:Lipodystrophy / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface / Q000378:metabolism; D054411:Receptors, Leptin; D051102:Serine C-Palmitoyltransferase; D015398:Signal Transduction; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
D002518:Ceramides; D003574:Cytochrome c Group; D005227:Fatty Acids; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D014280:Triglycerides; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; D020169:Caspases