TY - JOUR
T1 - Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria
AU - Rindler, Paul M.
AU - Crewe, Clair L.
AU - Fernandes, Jolyn
AU - Kinter, Michael
AU - Szweda, Luke I.
PY - 2013/9/1
Y1 - 2013/9/1
N2 - Obesity enhances the risk for the development of type 2 diabetes and cardiovascular disease. Loss in insulin sensitivity and diminished ability of muscle to take up and use glucose are characteristics of type 2 diabetes. Paradoxically, regulatory mechanisms that promote utilization of fatty acids appear to initiate diet-induced insulin insensitivity. In this review, we discuss recent findings implicating increased mitochondrial production of the prooxidant H2O2 due to enhanced utilization of fatty acids, as a signal to diminish reliance on glucose and its metabolites for energy. In the short term, the ability to preferentially use fatty acids may be beneficial, promoting a metabolic shift that ensures use of available fat by skeletal muscle and heart while preventing intracellular glucose accumulation and toxicity. However, with prolonged consumption of high dietary fat and ensuing obesity, the near exclusive dependence on fatty acid oxidation for production of energy by the mitochondria drives insulin resistance, diabetes, and cardiovascular disease.
AB - Obesity enhances the risk for the development of type 2 diabetes and cardiovascular disease. Loss in insulin sensitivity and diminished ability of muscle to take up and use glucose are characteristics of type 2 diabetes. Paradoxically, regulatory mechanisms that promote utilization of fatty acids appear to initiate diet-induced insulin insensitivity. In this review, we discuss recent findings implicating increased mitochondrial production of the prooxidant H2O2 due to enhanced utilization of fatty acids, as a signal to diminish reliance on glucose and its metabolites for energy. In the short term, the ability to preferentially use fatty acids may be beneficial, promoting a metabolic shift that ensures use of available fat by skeletal muscle and heart while preventing intracellular glucose accumulation and toxicity. However, with prolonged consumption of high dietary fat and ensuing obesity, the near exclusive dependence on fatty acid oxidation for production of energy by the mitochondria drives insulin resistance, diabetes, and cardiovascular disease.
KW - Insulin signaling
KW - Metabolic flexibility
KW - Mitochondria
KW - Obesity
KW - Redox signaling
UR - http://www.scopus.com/inward/record.url?scp=84883374607&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00799.2012
DO - 10.1152/ajpheart.00799.2012
M3 - Review article
C2 - 23792672
AN - SCOPUS:84883374607
SN - 0363-6135
VL - 305
SP - H634-H643
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -