Lysophosphatidylcholine as an effector of fatty acid-induced insulin resistance

Han, Myoung Sook; Lim, Yu-Mi; Quan, Wenying; Kim, Jung Ran; Chung, Kiseon; Kang, Mira; Kim, Sunshin; Park, Sun Young; Han, Joong‐Soo; Park, Shin-Young; Cheon, Hyae Gyeong; Rhee, Sang Dal; Park, Tae‐Sik; Lee, Myung-Shik

doi:10.1194/jlr.m014787

Cited by 119 publications

(86 citation statements)

References 56 publications

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“…We studied db/db mice on a C57BL/6J genetic background and characterized mitochondrial performance in key tissues for insulin action, including glycolytic and oxidative skeletal muscle and liver. Obese diabetic db/db mice are characterized by insulin resistance in glycolytic (22,43,52) and oxidative (6,19,35) skeletal muscle and liver (19,28,53). We provide evidence for tissue-specific changes in mitochondrial function in db/db mice, indicating that mitochondrial adaptations to an excessive nutrient supply and inactivity are influenced by the metabolic plasticity and function of each organ or cell type.…”

mentioning

confidence: 81%

Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes

Holmström

Iglesias‐Gutiérrez

Zierath

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

122

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The tissue-specific role of mitochondrial respiratory capacity in the development of insulin resistance and type 2 diabetes is unclear. We determined mitochondrial function in glycolytic and oxidative skeletal muscle and liver from lean (ϩ/?) and obese diabetic (db/db) mice. In lean mice, the mitochondrial respiration pattern differed between tissues. Tissuespecific mitochondrial profiles were then compared between lean and db/db mice. In liver, mitochondrial respiratory capacity and protein expression, including peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣), was decreased in db/db mice, consistent with increased mitochondrial fission. In glycolytic muscle, mitochondrial respiration, as well as protein and mRNA expression of mitochondrial markers, was increased in db/db mice, suggesting increased mitochondrial content and fatty acid oxidation capacity. In oxidative muscle, mitochondrial complex I function and PGC-1␣ and mitochondrial transcription factor A (TFAM) protein levels were decreased in db/db mice, along with increased level of proteins related to mitochondrial dynamics. In conclusion, mitochondrial respiratory performance is under the control of tissue-specific mechanisms and is not uniformly altered in response to obesity. Furthermore, insulin resistance in glycolytic skeletal muscle can be maintained by a mechanism independent of mitochondrial dysfunction. Conversely, insulin resistance in liver and oxidative skeletal muscle from db/db mice is coincident with mitochondrial dysfunction. mitochondrial dysfunction; mitochondrial biogenesis; oxidative capacity; energy metabolism OBESITY IS A MAJOR RISK FACTOR for development of insulin resistance and type 2 diabetes mellitus (T2DM) (49). Insulin resistance in skeletal muscle and liver, coupled with ␤-cell failure, represents underlying defects in T2DM. Thus, there is a growing appreciation that defects in insulin action in multiple tissues contribute to whole body insulin resistance, disturbances in energy balance, and T2DM.Mitochondrial dysfunction has been implicated in the development of insulin resistance and the pathogenesis of T2DM (32,37,38). The vast majority of mitochondrial proteins, as well as factors controlling the expression and proliferation of the mitochondrial genome, are encoded in the nucleus. Studies of rodent tissues, including analysis of mitochondrial DNA copy number, cytochrome c oxidase activity, and mitochondrial mass in liver, cardiac muscle, and oxidative and glycolytic skeletal muscle (8,9,14,50,51) provide evidence for marked tissue-specific differences in mitochondrial properties, concurrent with varying metabolic characteristics and demands unique to each specific tissue. Furthermore, quantitative mass spectrometry and 2-D gel electrophoresis of the mitochondrial proteome reveal tissue-specific mitochondrial protein programs (13,24,34). Mitochondria are finely tuned to meet the specific needs of the tissue as well as the environmental or pathophysiological state that the specific tissue encounters (1...

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mentioning

confidence: 81%

Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes

Holmström

Iglesias‐Gutiérrez

Zierath

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

122

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“…2 and 4). LPC [39], Cer and HexCer [40] generated during FATP4 and Pal sensitization could result in suppressed insulin sensitivity (Fig. 4C).…”

Section: Summarized Mechanisms For the Role Of Fatp4 In Lipoapoptosismentioning

confidence: 92%

Palmitate activation by fatty acid transport protein 4 as a model system for hepatocellular apoptosis and steatosis

Seeßle¹,

Liebisch

Schmitz

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Lipid residue after evaporation was suspended in 1% Triton X-100 in 100% ethanol, and mixed with Free Glycerol Reagent containing lipase (Sigma). After incubation at 37°C for 5 min, A 540 was measured for calculation of TG concentrations on a standard curve 61 .…”

Section: Methodsmentioning

confidence: 99%

“…After lipid loading, cells were treated with 100 nM insulin for 10 min, and immunoblot analysis was conducted to study insulin signalling. Primary hepatocytes were isolated from C57BL/6 mice using the retrograde two-step collagenase perfusion technique 61 . In brief, the liver was perfused with 10 ml of 1 Â Liver perfusion buffer (Gibco #17701), followed by perfusion with a second buffer (66.7 mM NaCl, 6.7 mM KCl, 4.8 mM CaCl 2 and 0.1 M HEPES, pH 7.6) containing 700 mg l À 1 collagenase (Sigma C5138) at a rate of 5 ml per min for 6 min.…”

Section: Methodsmentioning

confidence: 99%

Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes

et al. 2014

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Despite growing interest in the relationship between autophagy and systemic metabolism, how global changes in autophagy affect metabolism remains unclear. Here we show that mice with global haploinsufficiency of an essential autophagy gene (Atg7 þ / À mice) do not show metabolic abnormalities but develop diabetes when crossed with ob/ob mice. Atg7 þ / À -ob/ob mice show aggravated insulin resistance with increased lipid content and inflammatory changes, suggesting that autophagy haploinsufficiency impairs the adaptive response to metabolic stress. We further demonstrate that intracellular lipid content and insulin resistance after lipid loading are increased as a result of autophagy insufficiency, and provide evidence for increased inflammasome activation in Atg7 þ / À -ob/ob mice. Imatinib or trehalose improves metabolic parameters of Atg7 þ / À -ob/ob mice and enhances autophagic flux. These results suggest that systemic autophagy insufficiency could be a factor in the progression from obesity to diabetes, and autophagy modulators have therapeutic potential against diabetes associated with obesity and inflammation.

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Lysophosphatidylcholine as an effector of fatty acid-induced insulin resistance

Cited by 119 publications

References 56 publications

Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes

Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes

Palmitate activation by fatty acid transport protein 4 as a model system for hepatocellular apoptosis and steatosis

Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes

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