TY - JOUR
T1 - Diabetes and apoptosis
T2 - Lipotoxicity
AU - Kusminski, Christine
AU - Shetty, Shoba
AU - Orci, Lelio
AU - Unger, Roger H
AU - Scherer, Philipp E
N1 - Funding Information:
Acknowledgments We kindly thank Kate McCorkle for assistance with the figures. Our research is supported by NIH grants R01-DK55758 and R01-CA112023 (PES) and a JDRF post-doctoral fellowship 3-2008-130 (CMK).
PY - 2009/12
Y1 - 2009/12
N2 - Obesity is an established risk factor in the pathogenesis of insulin resistance, type 2 diabetes mellitus and cardiovascular disease; all components that are part of the metabolic syndrome. Traditionally, insulin resistance has been defined in a glucocentric perspective. However, elevated systemic levels of fatty acids are now considered significant contributors towards the pathophysiological aspects associated with the syndrome. An overaccumulation of unoxidized long-chain fatty acids can saturate the storage capacity of adipose tissue, resulting in a lipid 'spill over' to non-adipose tissues, such as the liver, muscle, heart, and pancreatic-islets. Under these circumstances, such ectopic lipid deposition can have deleterious effects. The excess lipids are driven into alternative non-oxidative pathways, which result in the formation of reactive lipid moieties that promote metabolically relevant cellular dysfunction (lipotoxicity) and programmed cell-death (lipoapoptosis). Here, we focus on how both of these processes affect metabolically significant cell-types and highlight how lipotoxicity and sequential lipoapoptosis are as major mediators of insulin resistance, diabetes and cardiovascular disease.
AB - Obesity is an established risk factor in the pathogenesis of insulin resistance, type 2 diabetes mellitus and cardiovascular disease; all components that are part of the metabolic syndrome. Traditionally, insulin resistance has been defined in a glucocentric perspective. However, elevated systemic levels of fatty acids are now considered significant contributors towards the pathophysiological aspects associated with the syndrome. An overaccumulation of unoxidized long-chain fatty acids can saturate the storage capacity of adipose tissue, resulting in a lipid 'spill over' to non-adipose tissues, such as the liver, muscle, heart, and pancreatic-islets. Under these circumstances, such ectopic lipid deposition can have deleterious effects. The excess lipids are driven into alternative non-oxidative pathways, which result in the formation of reactive lipid moieties that promote metabolically relevant cellular dysfunction (lipotoxicity) and programmed cell-death (lipoapoptosis). Here, we focus on how both of these processes affect metabolically significant cell-types and highlight how lipotoxicity and sequential lipoapoptosis are as major mediators of insulin resistance, diabetes and cardiovascular disease.
KW - Adiponectin
KW - Apoptosis
KW - Diabetes
KW - Leptin
KW - Lipotoxicity
KW - Pancreatic β-cells
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U2 - 10.1007/s10495-009-0352-8
DO - 10.1007/s10495-009-0352-8
M3 - Review article
C2 - 19421860
AN - SCOPUS:70449133334
VL - 14
SP - 1484
EP - 1495
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
SN - 1360-8185
IS - 12
ER -