title: Quantitative proteomic and functional analysis of liver mitochondria from high fat diet (HFD) diabetic mice.
abstract: Insulin resistance plays a major role in the development of type 2 diabetes and obesity and affects a number of biological processes such as mitochondrial biogenesis. Though mitochondrial dysfunction has been linked to the development of insulin resistance and pathogenesis of type 2 diabetes, the precise mechanism linking the two is not well understood. We used high fat diet (HFD)-induced obesity dependent diabetes mouse models to gain insight into the potential pathways altered with metabolic disease, and carried out quantitative proteomic analysis of liver mitochondria. As previously reported, proteins involved in fatty acid oxidation, branched chain amino acid degradation, tricarboxylic acid cycle, and oxidative phosphorylation were uniformly up-regulated in the liver of HFD fed mice compared with that of normal diet. Further, our studies revealed that retinol metabolism is distinctly down-regulated and the mitochondrial structural proteins-components of mitochondrial inter-membrane space bridging (MIB) complex (Mitofilin, Sam50, and ChChd3), and Tim proteins-essential for protein import, are significantly up-regulated in HFD fed mice. Structural and functional studies on HFD and normal diet liver mitochondria revealed remodeling of HFD mitochondria to a more condensed form with increased respiratory capacity and higher ATP levels compared with normal diet mitochondria. Thus, it is likely that the structural remodeling is essential to accommodate the increased protein content in presence of HFD: the mechanism could be through the MIB complex promoting contact site and crista junction formation and in turn facilitating the lipid and protein uptake.
authors.affiliation: Department of Pharmacology, and.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Guo
authors.forename: Manjula
authors.initials: M
authors.lastname: Darshi
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Ma
authors.forename: Guy A
authors.initials: GA
authors.lastname: Perkins
authors.forename: Zhouxin
authors.initials: Z
authors.lastname: Shen
authors.forename: Kristofer J
authors.initials: KJ
authors.lastname: Haushalter
authors.forename: Rintaro
authors.initials: R
authors.lastname: Saito
authors.forename: Ai
authors.initials: A
authors.lastname: Chen
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
authors.forename: Steven P
authors.initials: SP
authors.lastname: Briggs
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
authors.forename: Susan S
authors.initials: SS
authors.lastname: Taylor
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D025941:Protein Interaction Mapping; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014801:Vitamin A / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D024101:Mitochondrial Proteins; D020543:Proteome; D014801:Vitamin A; D000255:Adenosine Triphosphate
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