Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activation
Abstract
Hepatic steatosis, a hepatic component of metabolic syndrome, is common and may progress to steatohepatitis and cirrhosis. The liver X receptor-α (LXRα)-sterol regulatory element binding protein-1c (SREBP-1c) pathway plays a key role in hepatic steatosis. This study investigated the potential of ajoene, a stable garlic by-product, to inhibit high fat diet (HFD)-induced hepatic steatosis and the underlying mechanism. Ajoene treatment attenuated fat accumulation and induction of lipogenic genes in the liver of HFD-fed mice. Blood biochemical analyses and histopathologic examinations showed that ajoene prevented liver injury with the inhibition of oxidative stress, as evidenced by thiobarbituric acid reactive substances formation and nitrotyrosinylation. Moreover, ajoene treatment inhibited LXRα agonist (T0901317)-mediated SREBP-1c activation, and transactivation of the lipogenic target genes in hepatocytes. Ajoene was found to activate AMP-activated protein kinase (AMPK) via LKB1, responsible for the inhibition of p70 ribosomal S6 kinase-1 (S6K1). The ability of ajoene to repress T0901317-induced SREBP-1c expression was antagonized by inhibition of AMPK or activation of S6K1, supporting the role of these kinases in the antisteatotic effect. Our results demonstrate that ajoene has an effect of activating AMPK through LKB1 and inhibit S6K1 activity, contributing to the prevention of SREBP-1c-mediated hepatic lipogenesis via the inhibition of LXRα activity.
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Ajoene isolated from garlic extracts stimulates apoptosis, decreases fat accumulation in 3T3-L1 adipocytes, and dramatically decreases body weight gain in mice without affecting the amount of food intake.
“Ajoene isolated from garlic extracts was found to stimulate apoptosis, decrease the fat accumulation in 3T3-L1 adipocytes and dramatically decrease the body weight gain in mice without affecting the amount of food intake [117].”
From Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review (2020) · cites this paper as [117]
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Ajoene restored behavioral patterns and liver glutathione level in morphine treated C57BL6 mice
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- Authors
- Han, C. Y., Ki, S. H., Kim, Y. W., Noh, K., Lee, D. Y., Kang, B., Ryu, J.-H., Jeon, R., Kim, E. H., Hwang, S. J., & Kim, S. G.
- Affiliations
- Seoul National University (KR)
- Sookmyung Women's University (KR)
- Hanyang University (KR)
- Corresponding author
- Kim, Sang Geon
- ORCID
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2011-01-15
- Volume
- 14
- Issue
- 2
- Pages
- 187-202
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2086244440
- Cited by
- 63
- References
- 53
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Garlic and Onion Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- ajoene, hepatic steatosis, high-fat diet, liver X receptor alpha, SREBP-1c, AMPK, LKB1, S6K1, hepatic lipogenesis, oxidative stress, liver injury, metabolic syndrome
- MeSH terms
- Animals, Cells, Cultured, Dietary Fats, Disulfides, Enzyme Activation, Fatty Liver, Garlic, Humans, Male, Mice, Inbred C57BL, Sulfoxides, Molecular Structure, Protein Serine-Threonine Kinases, Oxidative Stress, Hepatocytes, Ribosomal Protein S6 Kinases, 90-kDa, Mice, AMP-Activated Protein Kinases
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