Author(s): Padmalayam I, Hasham S, Saxena U, Pillarisetti S
Objective: Lipoic acid synthase (LASY) is the enzyme that is involved in the endogenous synthesis of lipoic acid, a potent mitochondrial antioxidant. The aim of this study was to study the role of LASY in type 2 diabetes.
Research design and methods: We studied expression of LASY in animal models of type 2 diabetes. We also looked at regulation of LASY in vitro under conditions that exist in diabetes. Additionally, we looked at effects of LASY knockdown on cellular antioxidant status, inflammation, mitochondrial function, and insulin-stimulated glucose uptake.
Results: LASY expression is significantly reduced in tissues from animal models of diabetes and obesity compared with age- and sex-matched controls. In vitro, LASY mRNA levels were decreased by the proinflammatory cytokine tumor necrosis factor (TNF)-alpha and high glucose. Downregulation of the LASY gene by RNA interference (RNAi) reduced endogenous levels of lipoic acid, and the activities of critical components of the antioxidant defense network, increasing oxidative stress. Treatment with exogenous lipoic acid compensated for some of these defects. RNAi-mediated downregulation of LASY induced a significant loss of mitochondrial membrane potential and decreased insulin-stimulated glucose uptake in skeletal muscle cells. In endothelial cells, downregulation of LASY aggravated the inflammatory response that manifested as an increase in both basal and TNF-alpha-induced expression of the proinflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1). Overexpression of the LASY gene ameliorated the inflammatory response.
Conclusions: Deficiency of LASY results in an overall disturbance in the antioxidant defense network, leading to increased inflammation, insulin resistance, and mitochondrial dysfunction.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/19074983
Author(s): Bournat JC, Brown CW
Author(s): Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, et al.
Author(s): Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM
Author(s): Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J
Author(s): Khamaisi M, Potashnik R, Tirosh A, Demshchak E, Rudich A, et al.
Author(s): Konrad T, Vicini P, Kusterer K, Höflich A, Assadkhani A, et al.
Author(s): Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Barber A, Martínez JA, et al.
Author(s): Cicchillo RM, Booker SJ
Author(s): Yi X, Maeda N
Author(s): Navarro-Sastre A, Tort F, Stehling O, Uzarska MA, Arranz JA, et al.
Author(s): Mayr JA, Zimmermann FA, Fauth C, Bergheim C, Meierhofer D, et al.
Author(s): Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al.
Author(s): Gulick T, Cresci S, Caira T, Moore DD, Kelly DP
Author(s): Kim JM, Yoon M, Kang I, Kim SS, Ha J
Author(s): Jbilo O, Ravinet-Trillou C, Arnone M, Buisson I, Bribes E
Author(s): Ravinet Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, et al.
Author(s): Soares AF, Guichardant M, Cozzone D, Bernoud-Hubac N, Bouzaïdi-Tiali N
Author(s): Katsuki A, Suematsu M, Gabazza EC, Murashima S, Nakatani K, et al.
Author(s): Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, et al.
Author(s): Padmalayam I
Author(s): Cardinal P, Bellocchio L, Clark S, Cannich A, Klugmann M, et al.
Author(s): Addy C, Wright H, Van Laere K, Gantz I, Erondu N, et al.
Author(s): Zhou L, Sutton GM, Rochford JJ, Semple RK, Lam DD, et al.
Author(s): Gehlert DR, Rasmussen K, Shaw J, Li X, Ardayfio P, et al.
Author(s): Li B, Nolte LA, Ju JS, Han DH, Coleman T
Author(s): Church C, Lee S, Bagg EA, McTaggart JS, Deacon R, et al.
Author(s): Faraut B, Giannesini B, Matarazzo V, Le Fur Y, Rougon G, et al
Author(s): Pavón FJ, Serrano A, Pérez-Valero V, Jagerovic N, Hernández-Folgado L, et al.
Author(s): Kelley DE, He J, Menshikova EV, Ritov VB
Author(s): Conley KE, Jubrias SA, Esselman PC
Author(s): Rooyackers OE, Adey DB, Ades PA, Nair KS
Author(s): Chabi B, Ljubicic V, Menzies KJ, Huang JH, Saleem A, et al.
Author(s): Park SW, Goodpaster BH, Lee JS, Kuller LH, Boudreau R, et al.
Author(s): Park SW, Goodpaster BH, Strotmeyer ES, Kuller LH, Broudeau R, et al.
Author(s): St-Onge MP
Author(s): Ritov VB, Menshikova EV, Azuma K, Wood R, Toledo FG, et al.
Author(s): Djouadi F, Aubey F, Schlemmer D, Bastin J
Author(s): Poynten AM, Markovic TP, Maclean EL, Furler SM, Freund J, et al.
Author(s): Ginsberg HN