Abstract
Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha-lipoic acid (α-LA) has been demonstrated to function as an anti-inflammatory and anti-oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α-LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non-esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation-, lipid- and energy metabolism-related genes and proteins was determined by quantitative real-time polymerase chain reaction and western blotting. The results indicated that α-LA significantly decreased the epididymis fat weight index and the non-esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α-LA reduced their expression. The LPS-induced expression of nuclear factor-κB protein was decreased by α-LA. Regarding lipid metabolism, α-LA significantly counteracted the inhibitory effects of LPS on the expression of hormone-sensitive lipase gene and protein. α-LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α-LA significantly increased the expression of most of mitochondrial DNA-encoded genes compared with the control and LPS group. Accordingly, α-LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.
Similar content being viewed by others
Abbreviations
- α-LA:
-
Αlpha-lipoic acid
- LPS:
-
Lipopolysaccharide
- WAT:
-
White adipose tissue
- NF-κB:
-
Nuclear factor-κB
- TNF-α:
-
Tumor necrosis factor-α
- TLR4:
-
Toll-like receptor 4
- CON:
-
Control
- NEFA:
-
Non-esterified fatty acid
- PPIA:
-
Peptidylprolyl isomerase A
- HSL:
-
Hormone-sensitive lipase
- ATGL:
-
Adipose triglyceride lipase
- COX1:
-
Cytochrome c oxidase subunit 1
- IL-1α:
-
Interleukin-1α
- PPARγ:
-
Peroxisome proliferator-activated receptor γ
- C/EBPβ:
-
CAAT/enhancer-binding protein β
- SREBP1:
-
Sterol regulatory element-binding protein 1
- ACACA:
-
Acetyl-CoA carboxylase 1
- FASN:
-
Fatty acid synthase
- SCD1:
-
Stearoyl-CoA desaturase 1
- FATP1:
-
Fatty acid transport protein 1
- CD36:
-
Cluster of differentiation 36
- CPT-1a:
-
Carnitine palmitoyltransferase-1a
- ND1:
-
NADH dehydrogenase subunit 1
- ATF6:
-
ATP synthase F0 subunit 6
- CYTB:
-
Cytochrome b
- mtDNA:
-
Mitochondrial deoxyribonucleic acid
References
Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115:911–919 (quiz 920)
Zhang LJ, Guerrero-Juarez CF, Hata T, Bapat SP, Ramos R, Plikus MV, Gallo RL (2015) Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 347:67–71
Jordan SW, Cronan JE Jr (1997) A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J Biol Chem 272:17903–17906
Goraca A, Huk-Kolega H, Piechota A, Kleniewska P, Ciejka E, Skibska B (2011) Lipoic acid—biological activity and therapeutic potential. Pharmacol Rep 63:849–858
Rochette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C (2013) Direct and indirect antioxidant properties of alpha-lipoic acid and therapeutic potential. Mol Nutr Food Res 57:114–125
Hwang JS, An JM, Cho H, Lee SH, Park JH, Han IO (2015) A dopamine-alpha-lipoic acid hybridization compound and its acetylated form inhibit LPS-mediated inflammation. Eur J Pharmacol 746:41–49
Li G, Fu J, Zhao Y, Ji K, Luan T, Zang B (2015) Alpha-lipoic acid exerts anti-inflammatory effects on lipopolysaccharide-stimulated rat mesangial cells via inhibition of nuclear factor kappa B (NF-kappaB) signaling pathway. Inflammation 38:510–519
Lee CK, Lee EY, Kim YG, Mun SH, Moon HB, Yoo B (2008) Alpha-lipoic acid inhibits TNF-alpha induced NF-kappa B activation through blocking of MEKK1-MKK4-IKK signaling cascades. Int Immunopharmacol 8:362–370
Palsson-McDermott EM, O’Neill LA (2004) Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Immunology 113:153–162
Kang KP, Kim DH, Jung YJ, Lee AS, Lee S, Lee SY, Jang KY, Sung MJ, Park SK, Kim W (2009) Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation. Nephrol Dial Transplant 24:3012–3020
Liu Z, Guo J, Sun H, Huang Y, Zhao R, Yang X (2015) alpha-Lipoic acid attenuates LPS-induced liver injury by improving mitochondrial function in association with GR mitochondrial DNA occupancy. Biochimie 116:52–60
Reed LJ, De BB, Gunsalus IC, Hornberger CS Jr (1951) Crystalline alpha-lipoic acid; a catalytic agent associated with pyruvate dehydrogenase. Science 114:93–94
Golbidi S, Badran M, Laher I (2011) Diabetes and alpha lipoic Acid. Front Pharmacol 2:69
Wollin SD, Jones PJ (2003) Alpha-lipoic acid and cardiovascular disease. J Nutr 133:3327–3330
Feuerecker B, Pirsig S, Seidl C, Aichler M, Feuchtinger A, Bruchelt G, Senekowitsch-Schmidtke R (2012) Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo. Cancer Biol Ther 13:1425–1435
Suh SH, Lee KE, Kim IJ, Kim O, Kim CS, Choi JS, Choi HI, Bae EH, Ma SK, Lee JU, Kim SW (2015) Alpha-lipoic acid attenuates lipopolysaccharide-induced kidney injury. Clin Exp Nephrol 19:82–91
Shen HH, Lam KK, Cheng PY, Kung CW, Chen SY, Lin PC, Chung MT, Lee YM (2015) Alpha-lipoic acid prevents endotoxic shock and multiple organ dysfunction syndrome induced by endotoxemia in rats. Shock 43:405–411
Baldwin AS Jr (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683
Vig-Varga E, Benson EA, Limbil TL, Allison BM, Goebl MG, Harrington MA (2006) Alpha-lipoic acid modulates ovarian surface epithelial cell growth. Gynecol Oncol 103:45–52
Zhang WJ, Frei B (2001) Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 15:2423–2432
Song KH, Lee WJ, Koh JM, Kim HS, Youn JY, Park HS, Koh EH, Kim MS, Youn JH, Lee KU, Park JY (2005) alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem Biophys Res Commun 326:197–202
Yi X, Pashaj A, Xia M, Moreau R (2013) Reversal of obesity-induced hypertriglyceridemia by (R)-alpha-lipoic acid in ZDF (fa/fa) rats. Biochem Biophys Res Commun 439:390–395
Reue K (2011) A thematic review series: lipid droplet storage and metabolism: from yeast to man. J Lipid Res 52:1865–1868
Salinthone S, Yadav V, Schillace RV, Bourdette DN, Carr DW (2010) Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling. PloS One. doi:10.1371/journal.pone.0013058
Falkenberg M, Larsson NG, Gustafsson CM (2007) DNA replication and transcription in mammalian mitochondria. Annu Rev Biochem 76:679–699
Minocherhomji S, Tollefsbol TO, Singh KK (2012) Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 7:326–334
Dicter N, Madar Z, Tirosh O (2002) Alpha-lipoic acid inhibits glycogen synthesis in rat soleus muscle via its oxidative activity and the uncoupling of mitochondria. J Nutr 132:3001–3006
Wang L, Wu CG, Fang CQ, Gao J, Liu YZ, Chen Y, Chen YN, Xu ZG (2013) The protective effect of alpha-Lipoic acid on mitochondria in the kidney of diabetic rats. Int J Clin Exp Med 6:90–97
Hiller S, DeKroon R, Xu L, Robinette J, Winnik W, Alzate O, Simington S, Maeda N, Yi X (2014) alpha-Lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice. Free Radic Biol Med 71:362–367
Acknowledgments
This study was supported by the National Natural Science Foundation of China (31572482), the National Basic Science Research Program (973 program) of China (2015CB150300), the Program for New Century Excellent Talents in University (NCET-12-0889), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
About this article
Cite this article
Guo, J., Gao, S., Liu, Z. et al. Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice. Lipids 51, 1145–1152 (2016). https://doi.org/10.1007/s11745-016-4185-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-016-4185-2