Cited by 138Adipose Tissue and MetabolismRegulation of Appetite and ObesityPharmacology and Obesity Treatment

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The Chemical Uncoupler 2,4-Dinitrophenol (DNP) Protects against Diet-induced Obesity and Improves Energy Homeostasis in Mice at Thermoneutrality

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Goldgof, Margalit, Xiao, Cuiying, Chanturiya, Tatyana, Jou, William, Gavrilova, Oksana, Reitman, Marc L.·2014·Journal of Biological Chemistry

DOI 10.1074/jbc.m114.568204PMC PMC4094046

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Abstract

The chemical uncoupler 2,4-dinitrophenol (DNP) was an effective and widely used weight loss drug in the early 1930s. However, the physiology of DNP has not been studied in detail because toxicity, including hyperthermia and death, reduced interest in the clinical use of chemical uncouplers. To investigate DNP action, mice fed a high fat diet and housed at 30 °C (to minimize facultative thermogenesis) were treated with 800 mg/liter DNP in drinking water. DNP treatment increased energy expenditure by ∼ 17%, but did not change food intake. DNP-treated mice weighed 26% less than controls after 2 months of treatment due to decreased fat mass, without a change in lean mass. DNP improved glucose tolerance and reduced hepatic steatosis without observed toxicity. DNP treatment also reduced circulating T3 and T4 levels, Ucp1 expression, and brown adipose tissue activity, demonstrating that DNP-mediated heat generation substituted for brown adipose tissue thermogenesis. At 22 °C, a typical vivarium temperature that is below thermoneutrality, DNP treatment had no effect on body weight, adiposity, or glucose homeostasis. Thus, environmental temperature should be considered when assessing an anti-obesity drug in mice, particularly agents acting on energy expenditure. Furthermore, the beneficial effects of DNP suggest that chemical uncouplers deserve further investigation for the treatment of obesity and its comorbidities.

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Authors: Goldgof, M., Xiao, C., Chanturiya, T., Jou, W., Gavrilova, O., & Reitman, M. L.
Affiliations: National Institutes of Health (US)
Corresponding author: Reitman, Marc L.
ORCID: Goldgof, Margalit
Xiao, Cuiying
Gavrilova, Oksana
Reitman, Marc L.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2014-07
Volume: 289
Issue: 28
Pages: 19341-19350
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m114.568204
PMC: PMC4094046
OpenAlex: W2056400389
Cited by: 138
References: 52
Citations by year: 2026: 10 · 2025: 7 · 2024: 12 · 2023: 16 · 2022: 13 · 2021: 12 · 2020: 17 · 2019: 6 · 2018: 14 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 1
FWCI: 6.67
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 2263 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (DK075062, DK075063)
Topics: Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
Keywords: 2,4-dinitrophenol, diet-induced obesity, energy homeostasis, energy expenditure, thermoneutrality, brown adipose tissue thermogenesis, UCP1, glucose tolerance, hepatic steatosis, thyroid hormones, anti-obesity drugs, high-fat diet, fat mass
MeSH terms: Uncoupling Protein 1, Animals, Body Temperature Regulation, Adipose Tissue, Brown, Diet, Eating, Energy Metabolism, Gene Expression Regulation, Ion Channels, Obesity, Uncoupling Agents, 2,4-Dinitrophenol, Mitochondrial Proteins, Adiposity, Mice

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The Chemical Uncoupler 2,4-Dinitrophenol (DNP) Protects against Diet-induced Obesity and Improves Energy Homeostasis in Mice at Thermoneutrality

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