Leptin decreases lipogenic enzyme gene expression through modification of SREBP-1c gene expression in white adipose tissue of aging rats.
Aging is associated with a significant reduction of lipogenic enzyme gene expression and lipogenesis in white adipose tissue (WAT). The age-related increase of lep gene expression could be, in part, responsible for these changes. Considering that sterol regulatory element binding protein 1c (SREBP-1c) plays an important role in regulation of lipogenic enzyme gene expression, it is likely that the age-related decrease of WAT lipogenic potential could be a consequence of the inhibition of SREBP-1c gene expression by leptin. We determined whether the increase of lep gene expression would account for the age-related decrease in SREBP-1c and its direct target, main lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), by assaying the messenger RNA (mRNA) levels of SREBP-1c, FAS, ACC, and leptin in WAT of 2-month-old (young) and 20-month-old (old) rats. Leptin mRNA level was much higher in the old animals, whereas in contrast, old rats displayed much lower mRNA levels of SREBP-1c and lipogenic enzymes. Moreover, experimentally increased plasma leptin concentration in young rats to the value observed in old rats resulted in the decrease of SREBP-1c, FAS, and ACC mRNA levels in WAT. Thus, the increase of lep gene expression could, in part, account for the reduced SREBP-1c gene expression and, consequently, the diminished lipogenic activity in WAT of old animals.
Nogalska
Anna
A
Department of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, Poland.
Sucajtys-Szulc
Elzbieta
E
Swierczynski
Julian
J
D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000273:Adipose Tissue / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D064429:Fatty Acid Synthases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000235:genetics* / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase