Skip to main content Accessibility help

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

  • H. Sun (a1), Y. Huang (a1), C. Yin (a1), J. Guo (a1), R. Zhao (a1) and X. Yang (a1)...


Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body’s immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS.


Corresponding author



Hide All
Bobrovnikova-Marjon, E, Hatzivassiliou, G, Grigoriadou, C, Romero, M, Cavener, DR, Thompson, CB and Diehl, JA 2008. PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation. Proceedings of the National Academy of Sciences of the United States of America 105, 1631416319.
Bravo-Sagua, R, Rodriguez, AE, Kuzmicic, J, Gutierrez, T, Lopez-Crisosto, C, Quiroga, C, Díaz-Elizondo, J, Chiong, M, Gillette, TG, Rothermel, BA and Lavandero, S 2013. Cell death and survival through the endoplasmic reticulum-mitochondrial axis. Current Molecular Medicine 13, 317329.
Caton, PW, Nayuni, NK, Murch, O and Corder, R 2009. Endotoxin induced hyperlactatemia and hypoglycemia is linked to decreased mitochondrial phosphoenolpyruvate carboxykinase. Life Sciences 84, 738744.
De Marchi, U, Castelbou, C and Demaurex, N 2011. Uncoupling protein 3 (UCP3) modulates the activity of Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) by decreasing mitochondrial ATP production. The Journal of Biological Chemistry 286, 3253332541.
Frezza, C, Cipolat, S and Scorrano, L 2007. Organelle isolation: functional mitochondria from mouse liver, muscle and cultured filroblasts. Nature Protocols 2, 287295.
García-Martinez, C, Sibille, B, Solanes, G, Darimont, C, Macé, K, Villarroya, F and Gómez-Foix, AM 2001. Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane potential, raises ATP/ADP ratio, and favors fatty acid vs. glucose oxidation. The FASEB Journal 15, 20332035.
Glancy, B and Balaban, RS 2012. Role of mitochondrial Ca2+ in the regulation of cellular energetics. Biochemistry 51, 29592973.
Hotamisligil, GS 2010. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140, 900917.
Huang, Y, Liu, W, Yin, C, Ci, L, Zhao, R and Yang, X 2014. Response to lipopolysaccharide in salivary components and the submandibular gland of pigs. Livestock Science 167, 323330.
Isomura, M, Kotake, Y, Masuda, K, Miyara, M, Okuda, K, Samizo, S, Sanoh, S, Hosoi, T, Ozawa, K and Ohta, S 2013. Tributyltin-induced endoplasmic reticulum stress and its Ca(2+)-mediated mechanism. Toxicology and Applied Pharmacology 272, 137146.
James, AM, Collins, Y, Logan, A and Murphy, MP 2012. Mitochondrial oxidative stress and the metabolic syndrome. Trends In Endocrinology and Metabolism: TEM 23, 429434.
Jia, Y, Li, R, Cong, R, Yang, X, Sun, Q, Parvizi, N and Zhao, R 2013. Maternal low-protein diet affects epigenetic regulation of hepatic mitochondrial DNA transcription in a sex-specific manner in newborn piglets associated with GR binding to its promoter. PLoS One 8, E63855.
Joseph, SB, Castrillo, A, Laffitte, BA, Mangelsdorf, DJ and Tontonoz, P 2003. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nature Medicine 9, 213219.
Kaplowitz, N, Than, TA, Shinohara, M and Ji, C 2007. Endoplasmic reticulum stress and liver injury. Seminar Liver Disease 27, 367377.
Keinan, N, Pahima, H, Ben-Hail, D and Shoshan-Barmatz, V 2013. The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis. Biochimica Et Biophysica Acta 1833, 17451754.
Kim, SR, Kim, DI, Kang, MR, Lee, KS, Park, SY, Jeong, JS and Lee, YC 2013. Endoplasmic reticulum stress influences bronchial asthma pathogenesis by modulating nuclear factor kappaB activation. The Journal of Allergy and Clinical Immunology 132, 13971408.
Kozlov, AV, Duvigneau, JC, Miller, I, Nürnberger, S, Gesslbauer, B, Kungl, A, Ohlinger, W, Hartl, RT, Gille, L, Staniek, K, Gregor, W, Haindl, S and Redl, H 2009. Endotoxin causes functional endoplasmic reticulum failure, possibly mediated by mitochondria. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1792, 521530.
Kussmaul, L and Hirst, J 2006. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proceedings of the National Academy of Sciences of the United States of America 103, 76077612.
Lee, AH, Scapa, EF, Cohen, DE and Glimcher, LH 2008. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320, 14921496.
Lenzen, S 2014. A fresh view of glycolysis and glucokinase regulation: history and current status. Journal of Biological Chemistry 289, 1218912194.
Liu, TF, Vachharajani, VT, Yoza, BK and McCall, CE 2012. NAD+-dependent sirtuin 1 and 6 proteins coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response. The Journal of Biological Chemistry 287, 2575825769.
Maitra, SR, Gestring, ML, El-Maghrabi, MR, Lang, CH and Henry, MC 1999. Endotoxin-induced alterations in hepatic glucose-6-phosphatase activity and gene expression. Molecular and Cellular Biochemistry 196, 7983.
McCallum, RE and Berry, LJ 1973. Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver glycogen synthase in mice. Infection and Immunity 7, 642654.
Meng, ZX, Wang, L, Xiao, Y and Lin, JD 2014. The Baf60c/deptor pathway links skeletal muscle inflammation to glucose homeostasis in obesity. Diabetes 63, 15331545.
Metzger, S, Nusair, S, Planer, D, Barash, V, Pappo, O, Shilyansky, J and Chajek-Shaul, T 2004. Inhibition of hepatic gluconeogenesis and enhanced glucose uptake contribute to the development of hypoglycemia in mice bearing interleukin-1β-secreting tumor. Endocrinology 145, 51505156.
Minocherhomji, S, Tollefsbol, TO and Singh, KK 2012. Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 7, 326334.
Noh, H, Jeon, J and Seo, H 2014. Systemic injection of LPS induces region-specific neuroinflammation and mitochondrial dysfunction in normal mouse brain. Neurochemistry International 69, 3540.
Oyadomari, S, Harding, HP, Zhang, Y, Oyadomari, M and Ron, D 2008. Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metabolism 7, 520532.
Perreault, S, Bousquet, O, Lauzon, M, Paiement, J and Leclerc, N 2009. Increased association between rough endoplasmic reticulum membranes and mitochondria in transgenic mice that express P301L tau. Journal of Neuropathology & Experimental Neurology 68, 503514.
Pizzo, P, Drago, I, Filadi, R and Pozzan, T 2012. Mitochondrial Ca(2)(+) homeostasis: mechanism, role, and tissue specificities. Pflugers Archiv 464, 317.
Ritov, VB, Menshikova, EV, Azuma, K, Wood, R, Toledo, FG, Goodpaster, BH, Ruderman, NB and Kelley, DE 2010. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. American Journal of Physiology. Endocrinology and Metabolism 298, E49E58.
Rutkowski, DT, Wu, J, Back, SH, Callaghan, MU, Ferris, SP, Iqbal, J, Clark, R, Miao, H, Hassler, JR, Fornek, J, Katze, MG, Hussain, MM, Song, B, Swathirajan, J, Wang, J, Yau, GD and Kaufman, RJ 2008. UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Developmental Cell 15, 829840.
Suliman, HB, Welty-Wolf, KE, Carraway, M, Tatro, L and Piantadosi, CA 2004. Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis. Cardiovascular Research 64, 279288.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 1751-7311
  • EISSN: 1751-732X
  • URL: /core/journals/animal
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed