Glycerolipid Metabolism and Signaling in Health and Disease
Marc Prentki and
S. R. Murthy Madiraju
Departments of Nutrition and Biochemistry, University of Montreal, Montreal Diabetes Research Center, CR-CHUM, Montreal, Quebec, Canada H1W 4A4
Correspondence: Address all correspondence and requests for reprints to: Marc Prentki, Departments of Nutrition and Biochemistry, University of Montreal, Montreal Diabetes Research Center, CR-CHUM, Technopôle Angus, 2901, Rachel Est, Room 401E, Montreal, Quebec, Canada H1W 4A4. E-mail: marc.prentki{at}umontreal.ca; or S. R. Murthy Madiraju, Montreal Diabetes Research Center, CR-CHUM, Technopôle Angus, 2901, Rachel Est, Room 308, Montreal, Quebec, Canada H1W 4A4. E-mail: murthy.madiraju{at}crchum.qc.ca
Maintenance of body temperature is achieved partly by modulatinglipolysis by a network of complex regulatory mechanisms. Lipolysisis an integral part of the glycerolipid/free fatty acid (GL/FFA)cycle, which is the focus of this review, and we discuss thesignificance of this pathway in the regulation of many physiologicalprocesses besides thermogenesis.
GL/FFA cycle is referred to as a "futile" cycle because it involvescontinuous formation and hydrolysis of GL with the release ofheat, at the expense of ATP. However, we present evidence underscoringthe "vital" cellular signaling roles of the GL/FFA cycle formany biological processes. Probably because of its importancein many cellular functions, GL/FFA cycling is under stringentcontrol and is organized as several composite short substrate/productcycles where forward and backward reactions are catalyzed byseparate enzymes. We believe that the renaissance of the GL/FFAcycle is timely, considering the emerging view that many ofthe neutral lipids are in fact key signaling molecules whoseproduction is closely linked to GL/FFA cycling processes.
The evidence supporting the view that alterations in GL/FFAcycling are involved in the pathogenesis of "fatal" conditionssuch as obesity, type 2 diabetes, and cancer is discussed. Wealso review the different enzymatic and transport steps thatencompass the GL/FFA cycle leading to the generation of severalmetabolic signals possibly implicated in the regulation of biologicalprocesses ranging from energy homeostasis, insulin secretionand appetite control to aging and longevity. Finally, we presenta perspective of the possible therapeutic implications of targetingthis cycling.
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