Proposed involvement of adipocyte glyceroneogenesis and phosphoenolpyruvate carboxykinase in the metabolic syndrome.
Elevated concentration of plasma non-esterified fatty acids (NEFA) is now recognized as a key factor in the onset of insulin-resistance and type 2 diabetes mellitus. During fasting, circulating NEFAs arise from white adipose tissue (WAT) as a consequence of lipolysis from stored triacylglycerols. However, a significant part of these FAs (30-70%) is re-esterified within the adipocyte, so that a recycling occurs and net FA output is much less than << true >> lipolysis. Indeed, a balance between two antagonistic processes, lipolysis and FA re-esterification, controls the rate of net FA release from WAT. During fasting, re-esterification requires glyceroneogenesis defined as the de novo synthesis of glycerol-3-P from pyruvate, lactate or certain amino acids. The key enzyme in this process is the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C; EC 4.1.1.32). Recent advance has stressed the role of glyceroneogenesis and of PEPCK-C in FA release from WAT. Results indicate that glyceroneogenesis is indeed important to lipid homeostasis and that a disregulation in this pathway may have profound pathophysiological effects. The present review focuses on the regulation of glyceroneogenesis and of PEPCK-C gene expression and activity by FAs, retinoic acids, glucocorticoids and the hypolipidemic class of drugs, thiazolidinediones.
Cadoudal
Thomas
T
Inserm UMR-S 530; Université Paris5, Centre Universitaire, U.F.R. Biomédicale, 45, rue des Saints-Pères, 75006 Paris, France.
Leroyer
Stéphanie
S
Reis
André F
AF
Tordjman
Joan
J
Durant
Sylvie
S
Fouque
Françoise
F
Collinet
Martine
M
Quette
Joelle
J
Chauvet
Geneviève
G
Beale
Elmus
E
Velho
Gilberto
G
Antoine
Bénédicte
B
Benelli
Chantal
C
Forest
Claude
C
D017667:Adipocytes / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D004951:Esterification; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D005994:Glycerophosphates / Q000096:biosynthesis*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D024821:Metabolic Syndrome / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014212:Tretinoin / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D005230:Fatty Acids, Nonesterified; D005994:Glycerophosphates; D000960:Hypolipidemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; C500090:thiazolidine-2,4-dione; D014212:Tretinoin; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005990:Glycerol