Adipogenic signaling in rat white adipose tissue: modulation by aging and calorie restriction.
Alterations in adipogenesis could have significant impact on several aging processes. We previously reported that calorie restriction (CR) in rats significantly increases the level of circulating adiponectin, a distinctive marker of differentiated adipocytes, leading to a concerted modulation in the expression of key transcription target genes and, as a result, to increased fatty acid oxidation and reduced deleterious lipid accumulation in other tissues. These findings led us to investigate further the effects of aging on adipocytes and to determine how CR modulates adipogenic signaling in vivo. CR for 2 and 25 months, significantly increased the expression of PPARgamma, C/EBPbeta and Cdk-4, and partially attenuated age-related decline in C/EBPalpha expression relative to rats fed ad libitum (AL). As a result, adiponectin was upregulated at both mRNA and protein levels, resulting in activation of target genes involved in fatty acid oxidation and fatty acid synthesis, and greater responsiveness of adipose tissue to insulin. Moreover, CR significantly decreased the ratio of C/EBPbeta isoforms LAP/LIP, suggesting the suppression of gene transcription associated with terminal differentiation while facilitating preadipocytes proliferation. Morphometric analysis revealed a greater number of small adipocytes in CR relative to AL feeding. Immunostaining confirmed that small adipocytes were more strongly positive for adiponectin than the large ones. Overall these results suggest that CR increased the expression of adipogenic factors, and maintained the differentiated state of adipocytes, which is critically important for adiponectin biosynthesis and insulin sensitivity.
Zhu
Min
M
Laboratory of Experimental Gerontology, National Institute on Aging, 6200 Seaforth Street, Baltimore, MD 21224, USA.
Lee
Garrick D
GD
Ding
Liusong
L
Hu
Jingping
J
Qiu
Guang
G
de Cabo
Rafa
R
Bernier
Michel
M
Ingram
Donald K
DK
Zou
Sige
S
D042962:Acyl-CoA Oxidase / Q000235:genetics; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D031204:Caloric Restriction; D017931:DNA Primers / Q000235:genetics; D054890:Fatty Acid Synthase, Type I / Q000235:genetics; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
D052242:Adiponectin; D017931:DNA Primers; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D014157:Transcription Factors; D042962:Acyl-CoA Oxidase; D054890:Fatty Acid Synthase, Type I; D011972:Receptor, Insulin