β-aminoisobutyric acid attenuates LPS-induced inflammation and insulin resistance in adipocytes through AMPK-mediated pathway
Open accessAbstract
BACKGROUND: β-aminoisobutyric acid (BAIBA) is produced in skeletal muscle during exercise and has beneficial effects on obesity-related metabolic disorders such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to prevent high fat diet (HFD)-induced inflammation and insulin resistance in adipose tissue though anti-inflammatory effects in obesity. Previous reports have also demonstrated strong anti-inflammatory effects of BAIBA. METHODS: We used BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes. Insulin signaling-mediated proteins and inflammation markers were measured by Western blot analysis. Secretion of pro-inflammatory cytokines were measured by ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red-O. Statistical analysis was performed by ANOVA and student's t test. RESULTS: BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as lipid accumulation after full differentiation. We showed that BAIBA treatment stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner and lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as TNFα and MCP-1 was abrogated in BAIBA-treated 3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFκB and IκB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA significantly restored these changes. CONCLUSIONS: We demonstrated anti-inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3-L1 cells treated with LPS through AMPK-dependent signaling. These results provide evidence for the beneficial effects of BAIBA not only in liver and skeletal muscle cells but also in adipose tissue.
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BAIBA promotes increased visceral adipose tissue lipolysis, increased free fatty acid oxidation, and glucose uptake in skeletal muscle.
“BAIBA promotes increased VAT lipolysis, increased FFA oxidation, and glucose uptake in SkM [110,111,112].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [110]
The Discussion (page unavailable) reports that BAIBA stimulates fatty acid oxidation in skeletal muscle, citing earlier work. The Results and Discussion report increased fatty acid oxidation and glucose uptake in adipocytes, not glucose uptake in skeletal muscle. No passage establishes that BAIBA increases visceral adipose tissue lipolysis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe myokines METRNL and BAIBA have proven to suppress TNF-α and other proinflammatory cytokines both in vitro and in vivo.
“Similarly, the myokines METRNL [100] and BAIBA [110] have proven to suppress TNF-α and other proinflammatory cytokines both in vitro and in vivo (5).”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [110]
The Results section reports that BAIBA suppressed LPS-induced TNFα and MCP-1 secretion in cultured 3T3-L1 adipocytes, supporting the in vitro BAIBA claim. The Background mentions reduced inflammation in BAIBA-treated mice, but does not establish that TNFα and other cytokines were suppressed in vivo. This citation is attached to BAIBA, not METRNL. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBAIBA regulation is mediated through AMPK signaling and plays an important role in several pathologies.
“The regulation of BAIBA is mediated through AMPK signaling, and plays an important role in several pathologies.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Jung et al., 2018
The Results and Conclusion report that BAIBA activates AMPK and that its effects on inflammation and insulin resistance in adipocytes are mediated through AMPK signaling. They do not show that AMPK regulates BAIBA itself; the Conclusion also limits the proposed relevance chiefly to obesity-associated metabolic disorders, rather than pathologies generally. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBAIBA has an important therapeutic role against obesity, mainly by stimulating fatty acid oxidation, reducing lipogenesis in white adipose tissue, and attenuating inflammation and insulin resistance.
“BAIBA also has an important therapeutic role against obesity (Ginter and Simko, 2014), mainly by stimulating the oxidation of fatty acids, reducing the process of lipogenesis in WAT, and attenuating inflammation and insulin resistance (Jung et al., 2018).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Jung et al., 2018
The Discussion and Conclusion report that BAIBA stimulates fatty acid oxidation, suppresses lipogenic markers, and attenuates LPS-induced inflammation and insulin resistance in cultured adipocytes. They do not establish reduced lipogenesis in white adipose tissue in vivo; the broader therapeutic-role claim is cited separately to Ginter and Simko. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBAIBA attenuates hepatic apoptosis by reducing ER stress in hyperlipidemia and improves renal fibrosis.
“In addition to obesity, BAIBA is reported to attenuate hepatic apoptosis by reducing ER stress on hyperlipidemia and improving renal fibrosis (Jung et al., 2018).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Jung et al., 2018
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- Authors
- Jung, T. W., Park, H. S., Choi, G. H., Kim, D., & Lee, T.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Lee, Taeseung
- Venue
- Journal of Biomedical Science
- Published
- 2018-03-28
- Volume
- 25
- Issue
- 1
- Pages
- 27-27
- ISSN
- 1021-7770 (ISSN-L)
- 1423-0127
- PMC
- PMC5875012
- OpenAlex
- W2794526384
- Cited by
- 137
- References
- 40
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 22 · 2023: 24 · 2022: 24 · 2021: 9 · 2020: 9 · 2019: 11 · 2018: 3
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Journal of Biomedical Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Research Foundation of Korea (2016R1C1B2012674)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- beta-aminoisobutyric acid, AMPK, insulin resistance, adipocyte inflammation, lipopolysaccharide, 3T3-L1 adipocytes, adipogenesis, inflammatory cytokines, NF-κB signaling, insulin signaling, IRS-1, Akt, fatty acid oxidation, obesity
- MeSH terms
- Aminoisobutyric Acids, Animals, Inflammation, Insulin Resistance, Lipopolysaccharides, Signal Transduction, Adipocytes, 3T3-L1 Cells, Mice, AMP-Activated Protein Kinases
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