Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-23T03:48:07.587Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  11 February 2016

H. Sun
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
Y. Huang
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
C. Yin
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
J. Guo
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
R. Zhao
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
X. Yang*
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
*
Get access

Abstract

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.

Type
Research Article
Copyright
© The Animal Consortium 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
Frezza, C, Cipolat, S and Scorrano, L 2007. Organelle isolation: functional mitochondria from mouse liver, muscle and cultured filroblasts. Nature Protocols 2, 287295.Google Scholar
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.Google Scholar
Glancy, B and Balaban, RS 2012. Role of mitochondrial Ca2+ in the regulation of cellular energetics. Biochemistry 51, 29592973.CrossRefGoogle ScholarPubMed
Hotamisligil, GS 2010. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140, 900917.Google Scholar
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.CrossRefGoogle Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
Kaplowitz, N, Than, TA, Shinohara, M and Ji, C 2007. Endoplasmic reticulum stress and liver injury. Seminar Liver Disease 27, 367377.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
Lee, AH, Scapa, EF, Cohen, DE and Glimcher, LH 2008. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320, 14921496.Google Scholar
Lenzen, S 2014. A fresh view of glycolysis and glucokinase regulation: history and current status. Journal of Biological Chemistry 289, 1218912194.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
McCallum, RE and Berry, LJ 1973. Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver glycogen synthase in mice. Infection and Immunity 7, 642654.Google Scholar
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.Google Scholar
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.Google Scholar
Minocherhomji, S, Tollefsbol, TO and Singh, KK 2012. Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 7, 326334.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
Pizzo, P, Drago, I, Filadi, R and Pozzan, T 2012. Mitochondrial Ca(2)(+) homeostasis: mechanism, role, and tissue specificities. Pflugers Archiv 464, 317.CrossRefGoogle Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar