Saturated with fat: new perspectives on lipotoxicity.
OBJECTIVE
To present current perspectives on the mediators and mechanisms of cyto-lipotoxic events and their relevance to human health.


RESULTS
The relatively recent isolation of lipid acyltransferase genes from yeast to mice and humans has resulted in a paradigm shift that now establishes all fatty acids as toxic, albeit in tissue specific patterns and by different mechanisms. Furthermore, the dysregulation of glucose homeostasis in combination with excess fatty acids provides a synergistic effect leading to glucolipotoxicity and cell death. These findings are relevant to the development of disease states associated with the pathogenesis of the metabolic syndrome.


CONCLUSIONS
In an era when an astounding number of people are diagnosed with metabolic disorders, it is imperative that we understand the consequences of a chronic metabolic surplus. Excessive fat, saturated or otherwise, has to be accommodated. Multiple aspects of this homeostasis are emerging, some of which are described here.
Garbarino
Jeanne
J
Institute of Human Nutrition, Columbia University Medical Center, New York, New York 10032, USA.
Sturley
Stephen L
SL
D000273:Adipose Tissue / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D004041:Dietary Fats / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000378:metabolism; D009765:Obesity / Q000378:metabolism
D004041:Dietary Fats; D005227:Fatty Acids; D005947:Glucose