Lipoamide or lipoic acid stimulates mitochondrial biogenesis in 3T3-L1 adipocytes via the endothelial NO synthase–cGMP–protein kinase G signalling pathway
Open accessAbstract
BACKGROUND AND PURPOSE: Metabolic dysfunction due to loss of mitochondria plays an important role in diabetes, and stimulation of mitochondrial biogenesis by anti-diabetic drugs improves mitochondrial function. In a search for potent stimulators of mitochondrial biogenesis, we examined the effects and mechanisms of lipoamide and α-lipoic acid (LA) in adipocytes. EXPERIMENTAL APPROACH: Differentiated 3T3-L1 adipocytes were treated with lipoamide or LA. Mitochondrial biogenesis and possible signalling pathways were examined. KEY RESULTS: Exposure of 3T3-L1 cells to lipoamide or LA for 24 h increased the number and mitochondrial mass per cell. Such treatment also increased mitochondrial DNA copy number, protein levels and expression of transcription factors involved in mitochondrial biogenesis, including PGC-1α, mitochondrial transcription factor A and nuclear respiratory factor 1. Lipoamide produced these effects at concentrations of 1 and 10 µmol·L⁻¹, whereas LA was most effective at 100 µmol·L⁻¹. At 10 µmol·L⁻¹, lipoamide, but not LA, stimulated mRNA expressions of PPAR-γ, PPAR-α and CPT-1α. The potency of lipoamide was 10-100-fold greater than that of LA. Lipoamide dose-dependently stimulated expression of endothelial nitric oxide synthase (eNOS) and formation of cGMP. Knockdown of eNOS (with small interfering RNA) prevented lipoamide-induced mitochondrial biogenesis, which was also blocked by the soluble guanylate cyclase inhibitor, ODQ and the protein kinase G (PKG) inhibitor, KT5823. Thus, stimulation of mitochondrial biogenesis by lipoamide involved signalling via the eNOS-cGMP-PKG pathway. CONCLUSIONS AND IMPLICATIONS: Our data suggest that lipoamide is a potent stimulator of mitochondrial biogenesis in adipocyte, and may have potential therapeutic application in obesity and diabetes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NOS3 is expressed at highest relative abundance in vascular endothelium, but is also found in neurons, epithelial cells, cardiomyocytes, adipocytes, and hepatocytes.
“NOS3 (commonly called endothelial NOS or eNOS) is expressed to highest relative abundance in the vascular endothelium, but has also been found in neurons, epithelial cells, and cardiomyocytes [66] as well as adipocytes [67, 68] and hepatocytes [69-71].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Alpha-lipoic acid as a biological antioxidant
Packer, L., Witt, E. H., & Tritschler, H. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)00017-r · Cited by 1,995 · see citing works
Self-citationRoles of PPARs in health and disease
Kersten, S., Desvergne, B., & Wahli, W. (2000) · Nature · doi:10.1038/35013000 · Cited by 1,956 · see citing works
Guide to receptors and channels (GRAC), 5th edition
Alexander, S., Mathie, A., & Peters, J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01649_1.x · Cited by 1,947 · see citing works
Lehrke, M., & Lazar, M. A. (2005) · Cell · doi:10.1016/j.cell.2005.11.026 · Cited by 1,452 · see citing works
Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Nisoli, E., Clementi, E., Paolucci, C., Cozzi, V., Tonello, C., Sciorati, C., Bracale, R., Valerio, A., Francolini, M., Moncada, S., et al. (2003) · Science · doi:10.1126/science.1079368 · Cited by 1,243 · see citing works
Suh, J. H., Shenvi, S. V., Dixon, B. M., Liu, H., Jaiswal, A. K., Liu, R.-M., & Hagen, T. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400282101 · Cited by 774 · see citing works
Neuroprotection by the Metabolic Antioxidant α-Lipoic Acid
Packer, L., Tritschler, H. J., & Wessel, K. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00269-9 · Cited by 639 · see citing works
Self-citationMitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
Wilson-Fritch, L., Nicoloro, S., Chouinard, M., Lazar, M. A., Chui, P. C., Leszyk, J., Straubhaar, J., Czech, M. P., & Corvera, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21752 · Cited by 616 · see citing works
Gulick, T., Cresci, S., Caira, T., Moore, D. D., & Kelly, D. P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.11012 · Cited by 560 · see citing works
Boudina, S., Sena, S., O’Neill, B. T., Tathireddy, P., Young, M. E., & Abel, E. D. (2005) · Circulation · doi:10.1161/circulationaha.105.554360 · Cited by 502 · see citing works
Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
Nisoli, E., Falcone, S., Tonello, C., Cozzi, V., Palomba, L., Fiorani, M., Pisconti, A., Brunelli, S., Cardile, A., Francolini, M., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405432101 · Cited by 495 · see citing works
Wilson-Fritch, L., Burkart, A., Bell, G., Mendelson, K., Leszyk, J., Nicoloro, S., Czech, M., & Corvera, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.1085-1094.2003 · Cited by 459 · see citing works
Stevens, M. J., Obrosova, I. G., Cao, X., Huysen, C. V., & Greene, D. A. (2000) · Diabetes · doi:10.2337/diabetes.49.6.1006 · Cited by 366 · see citing works
α-Lipoic Acid in Liver Metabolism and Disease
Bustamante, J. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00371-7 · Cited by 349 · see citing works
STUDIES ON THE NATURE AND REACTIONS OF PROTEIN-BOUND LIPOIC ACID
Reed, L. J., Koike, M., Levitch, M. E., et al. (1958) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)70382-7 · Cited by 275 · see citing works
Liu, J. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9403-0 · Cited by 268 · see citing works
Self-citationThioctic (lipoic) acid: a therapeutic metal-chelating antioxidant?
Ou, P., Tritschler, H., & Wolff, S. P. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00116-h · Cited by 252 · see citing works
α-Lipoic Acid: A Metabolic Antioxidant and Potential Redox Modulator of Transcription
Packer, L., Roy, S., & Sen, C. K. (1996) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60980-1 · Cited by 240 · see citing works
Self-citationRole of adiponectin in human skeletal muscle bioenergetics
Civitarese, A. E., Ukropcova, B., Carling, S., Hulver, M., DeFronzo, R. A., Mandarino, L., Ravussin, E., & Smith, S. R. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.002 · Cited by 234 · see citing works
Evans, J. L., & Goldfine, I. D. (2000) · Diabetes Technology & Therapeutics · doi:10.1089/15209150050194279 · Cited by 228 · see citing works
Oxidative Stress Biology and Cell Injury During Type 1 and Type 2 Diabetes Mellitus
Maiese, K., Morhan, S. D., & Chong, Z. Z. (2007) · Current Neurovascular Research · doi:10.2174/156720207779940653 · Cited by 213 · see citing works
Mechanistic Insights Into Diabetes Mellitus and Oxidative Stress
Maiese, K., Chong, Z. Z., & Shang, Y. C. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707781058968 · Cited by 185 · see citing works
Borniquel, S., Valle, I., Cadenas, S., Lamas, S., & Monsalve, M. (2006) · The FASEB Journal · doi:10.1096/fj.05-5189fje · Cited by 147 · see citing works
Tedesco, L., Valerio, A., Cervino, C., Cardile, A., Pagano, C., Vettor, R., Pasquali, R., Carruba, M. O., Marsicano, G., Lutz, B., et al. (2008) · Diabetes · doi:10.2337/db07-1623 · Cited by 145 · see citing works
Liu, J., & Ames, B. N. (2005) · Nutritional Neuroscience · doi:10.1080/10284150500047161 · Cited by 138 · see citing works
Self-citationSun, L., Luo, C. Y., Long, J., Wei, D., & Liu, J. (2006) · Mitochondrion · doi:10.1016/j.mito.2006.04.003 · Cited by 128 · see citing works
Self-citationShen, W., Liu, K., Tian, C., Yang, L., Li, X., Ren, J., Packer, L., Cotman, C. W., & Liu, J. (2007) · Diabetologia · doi:10.1007/s00125-007-0852-4 · Cited by 102 · see citing works
Self-citationCho, K., Moon, H.-E., Moini, H., Packer, L., Yoon, D., & Chung, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210747200 · Cited by 88 · see citing works
Self-citationLipoic acid in health and disease.
Fuchs, J., Packer, L., & Zimmer, G. (1997) · Marcel Dekker eBooks · Cited by 87 · see citing works
Self-citation-Lipoic acid and -lipoamide prevent oxidant-induced lysosomal rupture and apoptosis
Persson, H. L., Svensson, A. I., & Brunk, U. T. (2001) · Redox Report · doi:10.1179/135100001101536472 · Cited by 59 · see citing works
Kanazawa, A., Nishio, Y., Kashiwagi, A., Inagaki, H., Kikkawa, R., & Horiike, K. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00255.2001 · Cited by 47 · see citing works
Choi, Y.-S., RYU, B., Min, H., Lee, S., & Pak, Y. K. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1338.009 · Cited by 33 · see citing works
Molecular Targets of Diabetic Vascular Complications and Potential New Drugs
ROS, R. D., Assaloni, R., & Ceriello, A. (2005) · Current Drug Targets · doi:10.2174/1389450054021855 · Cited by 27 · see citing works
Antioxidant Reactions of Dihydrolipoic Acid and Lipoamide with Triplet Duroquinone
Bisby, R. H., & Parker, A. W. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8245 · Cited by 19 · see citing works
Cheng, T., Chen, J. J. W., Chen, J. J., et al. (2009) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2008.05100.x · Cited by 15 · see citing works
Lipoamide influences substrate selection in post-ischaemic perfused rat hearts
Sümegi, B., Butwell, N. B., Malloy, C. R., et al. (1994) · Biochemical Journal · doi:10.1042/bj2970109 · Cited by 12 · see citing works
Diabetic neuropathy--choices of treatment.
Bruckner, I., Bustan, C., Adamescu, E., et al. (2002) · PubMed · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of obesity and insulin resistance by nitric oxide
Sansbury, B. E., & Hill, B. G. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.016 · Cited by 274 · see citing works
“highest relative abundance in the vascular endothelium, but has also been found in neurons, epithelial cells, and cardiomyocytes [66] as well as adipocytes [67,68] and hepatocytes [69–71].”
Background
- Authors
- Shen, W., Hao, J., Feng, Z., Tian, C., Chen, W., Packer, L., Shi, X., Zang, W., & Liu, J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Ocean University of China (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Tropical Agricultural Sciences (CN)
- University of Southern California (US)
- University of Kentucky (US)
- Xi'an Jiaotong University (CN)
- Corresponding author
- Liu, Jiankang
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2011-01-28
- Volume
- 162
- Issue
- 5
- Pages
- 1213-1224
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3051392
- OpenAlex
- W1605950857
- Cited by
- 52
- References
- 39
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 5
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2007CB512005, 973 Program, 30871002, 30930105, 30873058, 30770785, 81070325)
- Science and Technology Commission of Shanghai Municipality
- National Key Research and Development Program of China (2007CB5 12005)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- lipoamide, alpha-lipoic acid, mitochondrial biogenesis, adipocytes, endothelial nitric oxide synthase, cyclic GMP, protein kinase G, PGC-1α, mitochondrial DNA copy number, PPARγ, PPARα, carnitine palmitoyltransferase 1, diabetes mellitus, obesity, mitochondrial dysfunction
- MeSH terms
- Animals, Base Sequence, Carnitine O-Palmitoyltransferase, DNA, Mitochondrial, Cyclic GMP, Hypoglycemic Agents, Thioctic Acid, Mitochondria, Oxygen Consumption, RNA, Messenger, Signal Transduction, Adipocytes, Cyclic GMP-Dependent Protein Kinases, DNA Primers, Mitochondrial Proteins, 3T3-L1 Cells, Microscopy, Electron, Transmission, PPAR alpha, PPAR gamma, Mice, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
