Ursolic acid improves lipid and glucose metabolism in high‐fat‐fed C57BL/6J mice by activating peroxisome proliferator‐activated receptor alpha and hepatic autophagy

Jia, Yaoyao; Kim, Seyoung; Kim, Jiyoung; Kim, Bobae; Wu, Chunyan; Lee, Ji Hae; Jun, Hee‐jin; Kim, Nahyun; Lee, Dongho; Lee, Sung‐Joon

doi:10.1002/mnfr.201400399

Cited by 76Peroxisome Proliferator-Activated ReceptorsDiet, Metabolism, and DiseaseNatural Products and Biological Research

Ursolic acid improves lipid and glucose metabolism in high‐fat‐fed C57BL/6J mice by activating peroxisome proliferator‐activated receptor alpha and hepatic autophagy

Jia, Yaoyao, Kim, Seyoung, Kim, Jiyoung, Kim, Bobae, Wu, Chunyan, Lee, Ji Hae, Jun, Hee‐jin, Kim, Nahyun +2 more·2015·Molecular Nutrition & Food Research

DOI 10.1002/mnfr.201400399

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Abstract

Scope: This study investigated metabolic effects of ursolic acid (UA), a peroxisome proliferation‐activated receptor (PPAR)‐α activator, in vivo. Methods and results: High‐fat diet (HFD)‐fed C57BL/6J mice were orally administered UA (50 or 200 mg/kg body weight) for 8 wk. UA reduced liver and adipose tissue mass, adipocyte size, and plasma leptin concentrations, plasma triglyceride and low‐density‐lipoprotein cholesterol concentrations, while it elevated the high‐density‐lipoprotein cholesterol and adiponectin concentrations significantly compared with controls. UA induced the expression of PPARα and its responsive genes involved in fatty acid uptake and β‐oxidation in the livers, whereas genes involved in lipogenesis, including sterol regulatory element‐binding proteins‐1c, were downregulated. UA administration improved glucose tolerance and insulin sensitivity significantly compared with the HFD‐fed control livers. UA administration also activated hepatic autophagy as assessed by the expression of microtubule‐associated protein 1A/1B‐light chain 3 (LC3)‐II and other key proteins in the autophagy pathway. Conclusion: Our findings suggest that UA ameliorates lipid and glucose metabolism in HFD‐fed mice primarily by the activation of PPARα and induction of the hepatic autophagy pathway. Thus, intake of UA in the diet or in an isolated form may ameliorate lipid and glucose metabolism.

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Trials in several animal models have reported reductions in serum TC, TG, LDL-C or VLDL-C and/or increased HDL-C concentrations following oral administration of different doses of MA, OA or high but not low doses of ursolic acid.
“Trials in several animal models have also reported reductions in serum TC, TG, LDL-C or VLDL-C and/or increased HDL-C concentrations following oral administration of different doses (15–100 mg/kg/d) of MA [reviewed in 26], OA (5–25 mg/kg/d) [25–29] or high (200 mg/kg/d) but not low (50 mg/kg/d) doses of ursolic acid (UA) [30].”
From Olive pomace oil can improve blood lipid profile: a randomized, blind, crossover, controlled clinical trial in healthy and at-risk volunteers (2022) · cites this paper as [30]

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Authors: Jia, Y., Kim, S., Kim, J., Kim, B., Wu, C., Lee, J. H., Jun, H., Kim, N., Lee, D., & Lee, S.
Affiliations: Korea University (KR)
Department of Biotechnology Graduate School of Life Sciences & Biotechnology Korea University Seoul Republic of Korea
Department of Biosystems and Biotechnology Korea University Seoul Republic of Korea
Corresponding author: Lee, Sung‐Joon
ORCID: Jia, Yaoyao
Kim, Jiyoung
Lee, Ji Hae
Lee, Dongho
Lee, Sung‐Joon
Venue: Molecular Nutrition & Food Research
Publisher: Wiley
Published: 2014-12-22
Volume: 59
Issue: 2
Pages: 344-354
ISSN: 1613-4125 (ISSN-L)
1613-4133
DOI: 10.1002/mnfr.201400399
OpenAlex: W2004913822
Cited by: 76
References: 44
Citations by year: 2026: 4 · 2025: 5 · 2024: 3 · 2023: 10 · 2022: 5 · 2021: 7 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 1
FWCI: 2.60
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Molecular Nutrition & Food Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Research Foundation of Korea
Korea government (2013R1A2A2A01016176)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Health Sciences › Medicine › Surgery › Natural Products and Biological Research
Keywords: ursolic acid, PPARα activation, hepatic autophagy, high-fat diet, lipid metabolism, glucose metabolism, insulin sensitivity, glucose tolerance, fatty acid beta-oxidation, lipogenesis, SREBP-1c, adiponectin, leptin, HDL cholesterol, triglycerides, LC3-II, adipose tissue
MeSH terms: Ursolic Acid, Animals, Autophagy, Blood Glucose, Cholesterol, Fatty Acids, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Triglycerides, Triterpenes, Leptin, PPAR alpha, Lipogenesis, Carbohydrate Metabolism, Mice, Sterol Regulatory Element Binding Protein 1, Adiponectin, Diet, High-Fat

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Ursolic acid improves lipid and glucose metabolism in high‐fat‐fed C57BL/6J mice by activating peroxisome proliferator‐activated receptor alpha and hepatic autophagy

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