Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates lipid metabolism to control body fat accrual on a high-fat diet

Katherine E. Wortley; Guo Qing Chang; Zoya Davydova; Susan K. Fried; Sarah F. Leibowitz

doi:10.1016/j.regpep.2003.08.005

Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates lipid metabolism to control body fat accrual on a high-fat diet

Katherine E. Wortley, Guo Qing Chang, Zoya Davydova, Susan K. Fried, Sarah F. Leibowitz

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	89-99
Number of pages	11
Journal	Regulatory Peptides
Volume	117
Issue number	2
DOIs	https://doi.org/10.1016/j.regpep.2003.08.005
State	Published - 15 Feb 2004
Externally published	Yes

Keywords

Hypothalamus
Leptin
Non-esterified fatty acids
Obesity

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10.1016/j.regpep.2003.08.005

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title = "Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates lipid metabolism to control body fat accrual on a high-fat diet",

abstract = "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.",

keywords = "Hypothalamus, Leptin, Non-esterified fatty acids, Obesity",

author = "Wortley, {Katherine E.} and Chang, {Guo Qing} and Zoya Davydova and Fried, {Susan K.} and Leibowitz, {Sarah F.}",

note = "Funding Information: Whereas an elevation in leptin levels together with body fat is frequently associated with a rise in insulin levels [28,29] , the findings of the present investigation dissociated insulin from changes in CART. Specifically, while CART was elevated in all animal models that showed an increase in leptin levels, this effect occurred despite variable shifts in insulin, which were reduced in normal rats on a high-fat diet, while elevated with in obese rats. This dissociation was supported by the lack of significant correlations detected between CART mRNA and insulin. ",

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AU - Wortley, Katherine E.

AU - Chang, Guo Qing

AU - Davydova, Zoya

AU - Fried, Susan K.

AU - Leibowitz, Sarah F.

N1 - Funding Information: Whereas an elevation in leptin levels together with body fat is frequently associated with a rise in insulin levels [28,29] , the findings of the present investigation dissociated insulin from changes in CART. Specifically, while CART was elevated in all animal models that showed an increase in leptin levels, this effect occurred despite variable shifts in insulin, which were reduced in normal rats on a high-fat diet, while elevated with in obese rats. This dissociation was supported by the lack of significant correlations detected between CART mRNA and insulin.

PY - 2004/2/15

Y1 - 2004/2/15

N2 - 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.

AB - 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.

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Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates lipid metabolism to control body fat accrual on a high-fat diet

Abstract

Keywords

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