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CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis
OBJECTIVE: The cocaine- and amphetamine-regulated transcript (CART) codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART admin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784325/ https://www.ncbi.nlm.nih.gov/pubmed/29146410 http://dx.doi.org/10.1016/j.molmet.2017.10.015 |
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author | Lau, Jackie Farzi, Aitak Qi, Yue Heilbronn, Regine Mietzsch, Mario Shi, Yan-Chuan Herzog, Herbert |
author_facet | Lau, Jackie Farzi, Aitak Qi, Yue Heilbronn, Regine Mietzsch, Mario Shi, Yan-Chuan Herzog, Herbert |
author_sort | Lau, Jackie |
collection | PubMed |
description | OBJECTIVE: The cocaine- and amphetamine-regulated transcript (CART) codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been reported. METHODS: By combining Cart-cre knock-in mice with a Cart adeno-associated viral vector designed using the flip-excision switch (AAV-FLEX) technology, specific reintroduction or overexpression of CART selectively in CART neurons in the arcuate nucleus (Arc) and lateral hypothalamic area (LHA), respectively, was achieved. The effects on energy homeostasis control were investigated. RESULTS: Here we show that CART neuron-specific reintroduction of CART into the Arc and LHA leads to distinct effects on energy homeostasis control. Specifically, CART reintroduction into the Arc of otherwise CART-deficient Cart(cre/cre) mice markedly decreased fat mass and body weight, whereas CART reintroduction into the LHA caused significant fat mass gain and lean mass loss, but overall unaltered body weight. The reduced adiposity in Arc(CART);Cart(cre/cre) mice was associated with an increase in both energy expenditure and physical activity, along with significantly decreased Npy mRNA levels in the Arc but with no change in food consumption. Distinctively, the elevated fat mass in LHA(CART);Cart(cre/cre) mice was accompanied by diminished insulin responsiveness and glucose tolerance, greater spontaneous food intake, and reduced energy expenditure, which is consistent with the observed decrease of brown adipose tissue temperature. This is also in line with significantly reduced tyrosine hydroxylase (Th) and notably increased corticotropin-releasing hormone (Crh) mRNA expressions in the paraventricular nucleus (PVN). CONCLUSIONS: Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for the first time the distinct and region-specific functions of CART in controlling feeding and energy homeostasis. |
format | Online Article Text |
id | pubmed-5784325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57843252018-01-29 CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis Lau, Jackie Farzi, Aitak Qi, Yue Heilbronn, Regine Mietzsch, Mario Shi, Yan-Chuan Herzog, Herbert Mol Metab Original Article OBJECTIVE: The cocaine- and amphetamine-regulated transcript (CART) codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been reported. METHODS: By combining Cart-cre knock-in mice with a Cart adeno-associated viral vector designed using the flip-excision switch (AAV-FLEX) technology, specific reintroduction or overexpression of CART selectively in CART neurons in the arcuate nucleus (Arc) and lateral hypothalamic area (LHA), respectively, was achieved. The effects on energy homeostasis control were investigated. RESULTS: Here we show that CART neuron-specific reintroduction of CART into the Arc and LHA leads to distinct effects on energy homeostasis control. Specifically, CART reintroduction into the Arc of otherwise CART-deficient Cart(cre/cre) mice markedly decreased fat mass and body weight, whereas CART reintroduction into the LHA caused significant fat mass gain and lean mass loss, but overall unaltered body weight. The reduced adiposity in Arc(CART);Cart(cre/cre) mice was associated with an increase in both energy expenditure and physical activity, along with significantly decreased Npy mRNA levels in the Arc but with no change in food consumption. Distinctively, the elevated fat mass in LHA(CART);Cart(cre/cre) mice was accompanied by diminished insulin responsiveness and glucose tolerance, greater spontaneous food intake, and reduced energy expenditure, which is consistent with the observed decrease of brown adipose tissue temperature. This is also in line with significantly reduced tyrosine hydroxylase (Th) and notably increased corticotropin-releasing hormone (Crh) mRNA expressions in the paraventricular nucleus (PVN). CONCLUSIONS: Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for the first time the distinct and region-specific functions of CART in controlling feeding and energy homeostasis. Elsevier 2017-11-08 /pmc/articles/PMC5784325/ /pubmed/29146410 http://dx.doi.org/10.1016/j.molmet.2017.10.015 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Lau, Jackie Farzi, Aitak Qi, Yue Heilbronn, Regine Mietzsch, Mario Shi, Yan-Chuan Herzog, Herbert CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
title | CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
title_full | CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
title_fullStr | CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
title_full_unstemmed | CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
title_short | CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
title_sort | cart neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784325/ https://www.ncbi.nlm.nih.gov/pubmed/29146410 http://dx.doi.org/10.1016/j.molmet.2017.10.015 |
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