Jelenik 2017 Diabetes

From Bioblast
Publications in the MiPMap
Jelenik T, Kaul K, SΓ©quaris G, FlΓΆgel U, Phielix E, Kotzka J, Knebel B, Fahlbusch P, HΓΆrbelt T, Lehr S, Reinbeck AL, MΓΌller-Wieland D, Esposito I, Shulman GI, Szendroedi J, Roden M (2017) Mechanisms of insulin resistance in primary and secondary nonalcoholic fatty liver. Diabetes 66:2241-53.

Β» PMID: 28490610

Jelenik T, Kaul K, Sequaris G, Floegel U, Phielix E, Kotzka J, Knebel B, Fahlbusch P, Hoerbelt T, Lehr S, Reinbeck AL, Mueller-Wieland D, Esposito I, Shulman GI, Szendroedi J, Roden M (2017) Diabetes

Abstract: Nonalcoholic fatty liver disease is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific SREBP-1c overexpression as models of PRIM and SEC. PRIM mice featured increased lipogenic gene expression in the liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol content and protein kinase CΞ΅ translocation. SEC mice had decreased lipogenesis mediated by hepatic cholesterol responsive element-binding protein and featured portal/lobular inflammation along with total, whole-body insulin resistance. Hepatic mitochondrial respiration transiently increased and declined with aging along with higher muscle reactive oxygen species production. In conclusion, hepatic insulin resistance originates from lipotoxicity but not from lower mitochondrial capacity, which can even transiently adapt to increased peripheral lipolysis. Peripheral insulin resistance is prevented during increased hepatic lipogenesis only if adipose tissue lipid storage capacity is preserved.

Β© 2017 by the American Diabetes Association. β€’ Keywords: Sterol regulatory-element binding protein-1c (SREBP1c), Inflammation and oxidative stress, Insulin resistance, NAFLD, De novo lipogenesis β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: DE Duesseldorf Roden M, NL Maastricht Schrauwen P

Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Diabetes, Other 

Organism: Mouse  Tissue;cell: Skeletal muscle, Liver  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, NS, ROX  HRR: Oxygraph-2k 


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