Cited by 136Metabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic DiseasesDiet, Metabolism, and Disease

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A high-fat diet decreases AMPK activity in multiple tissues in the absence of hyperglycemia or systemic inflammation in rats

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Lindholm, Christopher R., Ertel, Rebecca L., Bauwens, Jake D., Schmuck, Eric G., Mulligan, Jacob D., Saupe, Kurt W.·2013·Journal of Physiology and Biochemistry

DOI 10.1007/s13105-012-0199-2PMC PMC3644018

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Abstract

Consumption of a high-fat diet (HFD) in experimental animal models initiates a series of molecular events and outcomes, including insulin resistance and obesity, that mimic the metabolic syndrome in humans. The relationship among, and order of, the molecular events linking a diet high in fat to pathologies is often unclear. In the present study, we provide several novel insights into the relationship between a HFD and AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism and whole-body energy balance. HFD substantially decreased the activities of both isoforms of AMPK in white adipose tissue, heart, and liver. These decreases in AMPK activity occurred in the absence of decreased AMPK transcription, systemic inflammation, hyperglycemia, or elevated levels of free fatty acids. The HFD-induced decrease in AMPK activity was associated with systemic insulin resistance and hyperleptinemia. In blood, >98 % of AMPK activity was localized in agranulocytes as the α1 isoform. In contrast to the solid tissues studied, AMPK activities were not altered by HFD in granulocytes or agranulocytes. We conclude that HFD-induced obesity causes a broad, non-tissue, or isoform-specific lowering of AMPK activity. Given the central position AMPK plays in whole-body energy balance, this decreased AMPK activity may play a previously unrecognized role in obesity and its associated pathologies.

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Mulligan JD, Gonzalez AA, Kumar R, Davis AJ, Saupe KW (2005) Aging elevates basal AMPK activity and eliminates hypoxic activation of AMPK in mouse liver. J Gerontol A Biol Sci Med Sci 60(1):21–27

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Authors: Lindholm, C. R., Ertel, R. L., Bauwens, J. D., Schmuck, E. G., Mulligan, J. D., & Saupe, K. W.
Affiliations: University of Wisconsin–Madison (US)
Corresponding author: Mulligan, Jacob D.
Saupe, Kurt W.
ORCID: Schmuck, Eric G.
Venue: Journal of Physiology and Biochemistry
Publisher: Springer Science and Business Media LLC
Published: 2012-09-02
Volume: 69
Issue: 2
Pages: 165-175
ISSN: 1138-7548 (ISSN-L)
1877-8755
DOI: 10.1007/s13105-012-0199-2
PMC: PMC3644018
OpenAlex: W1976242359
Cited by: 136
References: 60
Citations by year: 2026: 6 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 12 · 2021: 9 · 2020: 19 · 2019: 10 · 2018: 14 · 2017: 8 · 2016: 12 · 2015: 5 · 2014: 11 · 2013: 3 · 2012: 1
FWCI: 2.57
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Physiology and Biochemistry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (T32HL007936)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080345)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords: high-fat diet, AMPK, AMPK isoforms, obesity, insulin resistance, hyperleptinemia, white adipose tissue, heart, liver, agranulocytes, granulocytes, energy balance, metabolic syndrome, free fatty acids
MeSH terms: Animals, Adipose Tissue, Brown, Dietary Fats, Hyperglycemia, Inflammation, Male, Obesity, Organ Specificity, Rats, Sprague-Dawley, Rats, Adipose Tissue, White, AMP-Activated Protein Kinases, Diet, High-Fat

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A high-fat diet decreases AMPK activity in multiple tissues in the absence of hyperglycemia or systemic inflammation in rats

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