Rapid transformation of white adipocytes into fat-oxidizing machines.
Adenovirus-induced hyperleptinemia rapidly depletes body fat in normal rats without increasing free fatty acids and ketogenesis, implying that fat-storing adipocytes are oxidizing the fat. To analyze the ultrastructural changes of adipocytes accompanying this functional transformation, we examined the fat tissue by electron microscopy. After 14 days of hyperleptinemia, adipocytes had become shrunken, fatless, and encased in a thick basement-membrane-like matrix. They were crowded with mitochondria that were much smaller than those of brown adipocytes. Their gene expression profile revealed striking up-regulation of peroxisome proliferator-activated receptor gamma coactivator 1alpha (an up-regulator of mitochondrial biogenesis not normally expressed in white fat), increased uncoupling proteins-1 and -2, and down-regulation of lipogenic enzymes. Phosphorylation of both acetyl CoA carboxylase and AMP-activated protein kinase was increased, thus explaining the increase in fatty acid oxidation. The ability to transform adipocytes into unique fat-burning cells may suggest novel therapeutic strategies for obesity.
Orci
Lelio
L
Department of Morphology, University of Geneva Medical School, Rue Michel Servet 1, CH 1211 Geneva 4, Switzerland. lelio.orci@medecine.unige.ch
Cook
William S
WS
Ravazzola
Mariella
M
Wang
May-Yun
MY
Park
Byung-Hyun
BH
Montesano
Roberto
R
Unger
Roger H
RH
D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015415:Biomarkers; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008928:Mitochondria / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014157:Transcription Factors / Q000235:genetics
D015415:Biomarkers; D020738:Leptin; D016877:Oxidants; D012333:RNA, Messenger; D014157:Transcription Factors