OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization.
Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47) family regulate cellular neutral lipid stores. We have studied a new member of this family, PAT-1, and found that it is expressed in highly oxidative tissues. We refer to this protein as "OXPAT." Physiologic lipid loading of mouse liver by fasting enriches OXPAT in the lipid droplet tissue fraction. OXPAT resides on lipid droplets with the PAT protein adipophilin in primary cardiomyocytes. Ectopic expression of OXPAT promotes fatty acid-induced triacylglycerol accumulation, long-chain fatty acid oxidation, and mRNAs associated with oxidative metabolism. Consistent with these observations, OXPAT is induced in mouse adipose tissue, striated muscle, and liver by physiological (fasting), pathophysiological (insulin deficiency), pharmacological (peroxisome proliferator-activated receptor [PPAR] agonists), and genetic (muscle-specific PPARalpha overexpression) perturbations that increase fatty acid utilization. In humans with impaired glucose tolerance, PPARgamma agonist treatment induces adipose OXPAT mRNA. Further, adipose OXPAT mRNA negatively correlates with BMI in nondiabetic humans. Our collective data in cells, mice, and humans suggest that OXPAT is a marker for PPAR activation and fatty acid oxidation. OXPAT likely contributes to adaptive responses to the fatty acid burden that accompanies fasting, insulin deficiency, and overnutrition, responses that are defective in obesity and type 2 diabetes.
Wolins
Nathan E
NE
Department of Medicine, 660 S. Euclid Ave., Campus Box 8127, St. Louis, MO 63110, USA.
Quaynor
Benjamin K
BK
Skinner
James R
JR
Tzekov
Anatoly
A
Croce
Michelle A
MA
Gropler
Matthew C
MC
Varma
Vijayalakshmi
V
Yao-Borengasser
Aiwei
A
Rasouli
Neda
N
Kern
Philip A
PA
Finck
Brian N
BN
Bickel
Perry E
PE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D017931:DNA Primers; D005227:Fatty Acids / Q000378:metabolism*; D016678:Genome; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000166:cytology / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*
D017931:DNA Primers; D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; C516105:OXPAT protein, mouse; D010446:Peptide Fragments; D047492:Peroxisome Proliferator-Activated Receptors; D019308:Palmitic Acid