Volume 19, Issue 10, Pages (June 2017)

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Volume 19, Issue 10, Pages 1997-2004 (June 2017) Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans Kasper W. ter Horst, Pim W. Gilijamse, Ruth I. Versteeg, Mariette T. Ackermans, Aart J. Nederveen, Susanne E. la Fleur, Johannes A. Romijn, Max Nieuwdorp, Dongyan Zhang, Varman T. Samuel, Daniel F. Vatner, Kitt F. Petersen, Gerald I. Shulman, Mireille J. Serlie Cell Reports Volume 19, Issue 10, Pages 1997-2004 (June 2017) DOI: 10.1016/j.celrep.2017.05.035 Copyright © 2017 The Author(s) Terms and Conditions

Cell Reports 2017 19, 1997-2004DOI: (10.1016/j.celrep.2017.05.035) Copyright © 2017 The Author(s) Terms and Conditions

Figure 1 The Presence of Hepatic Steatosis, but Not Its Extent, Is Associated with Insulin Resistance in Obese Humans (A) The basal rate of EGP was assessed after an overnight fast. (B) Hepatic insulin sensitivity is expressed as the insulin-mediated suppression of basal EGP. (C) Adipose tissue insulin sensitivity is expressed as the insulin-mediated suppression of circulating FA. (D) Peripheral insulin sensitivity is expressed as the insulin-stimulated Rd of glucose. Data are mean ± SEM (n = 125–133). ∗∗∗p ≤ 0.001. Cell Reports 2017 19, 1997-2004DOI: (10.1016/j.celrep.2017.05.035) Copyright © 2017 The Author(s) Terms and Conditions

Figure 2 Relationships between IHTG Content and Tissue-Specific Measurements of Insulin Sensitivity in Obese Subjects Were Best Described by Nonlinear Models (A) Hepatic insulin sensitivity. (B) Adipose tissue insulin sensitivity. (C) Peripheral insulin sensitivity. Lines are best fit and 95% CI (n = 125–133). Cell Reports 2017 19, 1997-2004DOI: (10.1016/j.celrep.2017.05.035) Copyright © 2017 The Author(s) Terms and Conditions

Figure 3 Hepatic Insulin Resistance Was Strongly Associated with Elevated DAG Content in the Cytosolic Fraction and PKCε Translocation (A) Hepatic ceramide content in obese subjects with normal hepatic insulin sensitivity or hepatic insulin resistance. (B) Total hepatic DAG content. (C) Hepatic DAG content in cytosolic fraction. (D) Hepatic DAG content in membrane fraction. (E) Individual DAG species in hepatic cytosol. Note the segmented y axis. (F) Representative bands show PKCε translocation from cytosol to membrane. (G) Translocation of PKCε from cytosol (c) to membrane (m) as an index of activation. Data are mean ± SEM (n = 18–29). ∗p < 0.05. ∗∗p < 0.01. ∗∗∗p = 0.001. Cell Reports 2017 19, 1997-2004DOI: (10.1016/j.celrep.2017.05.035) Copyright © 2017 The Author(s) Terms and Conditions