AMPK, the metabolic syndrome and cancer

Luo, Zhijun; Saha, Asish K.; Xiang, Xiaoqin; Ruderman, Neil B.

doi:10.1016/j.tips.2004.12.011

Cited by 426Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerPeroxisome Proliferator-Activated Receptors

AMPK, the metabolic syndrome and cancer

Luo, Zhijun, Saha, Asish K., Xiang, Xiaoqin, Ruderman, Neil B.·2005·Trends in Pharmacological Sciences

DOI 10.1016/j.tips.2004.12.011

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Abstract

The fuel-sensing enzyme 5'-AMP-activated protein kinase (AMPK) has a major role in the regulation of cellular lipid and protein metabolism in response to stimuli such as exercise, changes in fuel availability and the adipocyte-derived hormones leptin and adiponectin. Recent studies indicate that abnormalities in cellular lipid metabolism are involved in the pathogenesis of the metabolic syndrome, possibly because of dysregulation of AMPK and malonyl-CoA, a closely related molecule. As we discuss in this article, several findings also point to a link between AMPK and the growth and/or survival of some cancer cells. Thus, it has been demonstrated recently that the tumor suppressor LKB1 is a kinase that has a major role in phosphorylating and activating AMPK, and that another tumor suppressor, tuberous sclerosis complex 2, is phosphorylated and activated by AMPK. In addition, other studies indicate that mammalian homolog of target of rapamycin (mTOR), which has been implicated in the pathogenesis of insulin resistance and many types of cancer, is inhibited by AMPK.

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A decrease in ACC activity reduces the levels of intracellular malonyl-CoA, an allosteric inhibitor of CPT1, allowing CPT1 to transfer long-chain fatty acids into mitochondria for oxidation.
“A decrease in ACC activity reduces the levels of intracellular malonyl-CoA, an allosteric inhibitor of CPT1. Hence, CPT1 can assume the transfer of long-chain fatty acids from the cytosol into the mitochondria, where they are oxidized [45,46].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [45]
AMPK increases fatty-acid oxidation by inhibiting ACC2 through phosphorylation.
“Eventually, AMPK further increases fatty-acid oxidation by inhibiting acetyl-CoA carboxylase 2 (ACC2) through phosphorylation (Figure 2).”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [45]

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Authors: Luo, Z., Saha, A. K., Xiang, X., & Ruderman, N. B.
Affiliations: Boston University (US)
Corresponding author: Luo, Zhijun
ORCID: Luo, Zhijun
Saha, Asish K.
Ruderman, Neil B.
Venue: Trends in Pharmacological Sciences
Publisher: Elsevier BV
Published: 2005-02
Volume: 26
Issue: 2
Pages: 69-76
ISSN: 0165-6147 (ISSN-L)
DOI: 10.1016/j.tips.2004.12.011
OpenAlex: W2022474551
Cited by: 426
References: 86
Citations by year: 2026: 3 · 2025: 11 · 2024: 10 · 2023: 6 · 2022: 13 · 2021: 11 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 16 · 2016: 30 · 2015: 21 · 2014: 29 · 2013: 35 · 2012: 29
FWCI: 2.08
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Pharmacological Sciences (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01dk019514-35)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 19417, DK-19514)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: AMPK, metabolic syndrome, cancer, lipid metabolism, malonyl-CoA, leptin, adiponectin, LKB1, tuberous sclerosis complex 2, mTOR, insulin resistance, tumor suppressor
MeSH terms: Animals, Expert Testimony, Humans, Multienzyme Complexes, Neoplasms, Protein Serine-Threonine Kinases, Genetic Predisposition to Disease, Metabolic Syndrome, AMP-Activated Protein Kinases

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