Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates lipid metabolism to control body fat accrual on a high-fat diet.
Previous studies have indicated a relationship between cocaine- and amphetamine-related transcript (CART) and leptin. The present study used quantitative PCR and in situ hybridization to examine this CART-leptin relationship in different animal models. With CART injection, the function of this pathway was also investigated. The results demonstrate that CART mRNA in the arcuate nucleus (ARC) was significantly increased in subjects fed a high-fat diet (HFD) compared to low-fat diet (LFD). It was also elevated in obese vs. lean rats and in normal-weight obesity-prone vs. obesity-resistant rats. In each group tested, CART mRNA in the ARC was positively correlated specifically with circulating levels of leptin. Its close association specifically with leptin was further supported by a stimulatory effect of this hormone on CART expression. This leptin-CART relationship in the ARC, in contrast, was less consistent or undetectable in the paraventricular nucleus and lateral hypothalamus. Central injection of CART peptide (55-102) increased circulating non-esterified fatty acid levels and decreased lipoprotein lipase activity in adipose tissue. These results suggest that, on a fat-rich diet, this leptin-CART pathway originating in the ARC inhibits excessive body fat accrual by causing a shift from lipid storage toward lipid mobilization.
Wortley
Katherine E
KE
The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Chang
Guo-Qing
GQ
Davydova
Zoya
Z
Fried
Susan K
SK
Leibowitz
Sarah F
SF
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001823:Body Composition; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage*; D015870:Gene Expression; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D004041:Dietary Fats; D020738:Leptin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D008071:Lipoprotein Lipase