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Cited by 127Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesMetabolism, Diabetes, and Cancer

Regulation of hypothalamic malonyl-CoA by central glucose and leptin

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Wolfgang, Michael J., Cha, Seung Hun, Sidhaye, Aniket, Chohnan, Shigeru, Cline, Gary, Shulman, Gerald I., Lane, M. Daniel·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0709778104PMC PMC2148282
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Abstract

Hypothalamic malonyl-CoA has been shown to function in global energy homeostasis by modulating food intake and energy expenditure. Little is known, however, about the regulation of malonyl-CoA concentration in the central nervous system. To address this issue we investigated the response of putative intermediates in the malonyl-CoA pathway to metabolic and endocrine cues, notably those provoked by glucose and leptin. Hypothalamic malonyl-CoA rises in proportion to the carbohydrate content of the diet consumed after food deprivation. Malonyl-CoA concentration peaks 1 h after refeeding or after peripheral glucose administration. This response depends on the dose of glucose administered and is blocked by the i.c.v. administration of an inhibitor of glucose metabolism, 2-deoxyglucose (2-DG). The kinetics of change in hypothalamic malonyl-CoA after glucose administration is coincident with the suppression of phosphorylation of AMP kinase and acetyl-CoA carboxylase. Blockade of glucose utilization in the CNS by i.c.v. 2-DG prevented the effects of glucose on 5′AMP-activated protein kinase, malonyl-CoA, hypothalamic neuropeptide expression, and food intake. Finally, we showed that leptin can increase hypothalamic malonyl-CoA and that the increase is additive with glucose administration. Leptin-deficient ob / ob mice, however, showed no defect in the glucose- or refeeding-induced rise in hypothalamic malonyl-CoA after food deprivation, demonstrating that leptin was not required for this effect. These studies show that hypothalamic malonyl-CoA responds to the level of circulating glucose and leptin, both of which affect energy homeostasis.

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Crossref · 10.1073/pnas.0709778104

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  • Increased malonyl-CoA levels, which are generated by activated (i.e., dephosphorylated) ACC, act as abundance indicators, thereby diminishing food intake and consequently body weight.

    “Strong evidence shows that increased malonyl-CoA levels, which are generated by activated (*i.e.,* dephosphorylated) ACC, act as abundance indicators, thereby diminishing food intake and consequently body weight ([173](#B173)).”

    From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [173]

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Authors
Wolfgang, M. J., Cha, S. H., Sidhaye, A., Chohnan, S., Cline, G., Shulman, G. I., & Lane, M. D.
Affiliations
  • Johns Hopkins University (US)
  • Ibaraki University (JP)
  • Howard Hughes Medical Institute (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-12-04
Volume
104
Issue
49
Pages
19285-19290
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0709778104
PMC
PMC2148282
OpenAlex
W1970637709
Cited by
127
References
33
Citations by year
2026: 1 · 2025: 6 · 2024: 5 · 2022: 2 · 2021: 3 · 2020: 9 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 13 · 2012: 7
FWCI
5.17
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK-38418, P30DK45735, DK40936, U24DK76169, R01DK040936, U24DK059635, U24DK076169, R01DK038418, P30DK045735)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
glucose, leptin, energy homeostasis, dietary intake, AMPK, acetyl-CoA carboxylase, 2-deoxyglucose, refeeding, food deprivation, neuropeptide expression, ob/ob mice
MeSH terms
Acetyl-CoA Carboxylase, Adenylate Kinase, Animals, Antimetabolites, Blood Glucose, Deoxyglucose, Dietary Carbohydrates, Fatty Acids, Glucose, Hypothalamus, Malonyl Coenzyme A, Mice, Mutant Strains, Phosphorylation, Pro-Opiomelanocortin, Leptin, Mice, Agouti-Related Protein

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