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Chennamsetty 2016 Cell Rep

From Bioblast
Publications in the MiPMap
Chennamsetty I, Coronado M, Contrepois K, Keller MP, Carcamo-Orive I, Sandin J, Fajardo G, Whittle AJ, Fathzadeh M, Snyder M, Reaven G, Attie AD, Bernstein D, Quertermous T, Knowles JW (2016) Nat1 deficiency is associated with mitochondrial dysfunction and exercise intolerance in mice. Cell Rep 17:527-40.

Β» PMID: 27705799 Open Access

Chennamsetty I, Coronado M, Contrepois K, Keller MP, Carcamo-Orive I, Sandin J, Fajardo G, Whittle AJ, Fathzadeh M, Snyder M, Reaven G, Attie AD, Bernstein D, Quertermous T, Knowles JW (2016) Cell Rep

Abstract: We recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial dysfunction characterized by increased intracellular reactive oxygen species and mitochondrial fragmentation as well as decreased mitochondrial membrane potential, biogenesis, mass, cellular respiration, and ATP generation. These effects were consistent in 3T3-L1 adipocytes, C2C12 myoblasts, and in tissues from Nat1-deficient mice, including white adipose tissue, heart, and skeletal muscle. Nat1-deficient mice had changes in plasma metabolites and lipids consistent with a decreased ability to utilize fats for energy and a decrease in basal metabolic rate and exercise capacity without altered thermogenesis. Collectively, our results suggest that Nat1 deficiency results in mitochondrial dysfunction, which may constitute a mechanistic link between this gene and IR.

Copyright Β© 2016 The Authors. Published by Elsevier Inc. All rights reserved. β€’ Keywords: NAT2, Nat1, Adipose tissue, Basal metabolic rate, Fatty acids, Insulin resistance, Mitochondria, Mitochondrial dysfunction, Reactive oxygen species

β€’ O2k-Network Lab: US GA Atlanta Langley T


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Mouse  Tissue;cell: Heart, Fat  Preparation: Isolated mitochondria 



HRR: Oxygraph-2k 

2016-11