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Adipocyte JAK2 mediates growth hormone–induced hepatic insulin resistance
Kevin C. Corbit, … , Michael J. Jurczak, Ethan J. Weiss
Kevin C. Corbit, … , Michael J. Jurczak, Ethan J. Weiss
Published February 9, 2017
Citation Information: JCI Insight. 2017;2(3):e91001. https://doi.org/10.1172/jci.insight.91001.
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Research Article Endocrinology Metabolism

Adipocyte JAK2 mediates growth hormone–induced hepatic insulin resistance

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Abstract

For nearly 100 years, growth hormone (GH) has been known to affect insulin sensitivity and risk of diabetes. However, the tissue governing the effects of GH signaling on insulin and glucose homeostasis remains unknown. Excess GH reduces fat mass and insulin sensitivity. Conversely, GH insensitivity (GHI) is associated with increased adiposity, augmented insulin sensitivity, and protection from diabetes. Here, we induce adipocyte-specific GHI through conditional deletion of Jak2 (JAK2A), an obligate transducer of GH signaling. Similar to whole-body GHI, JAK2A mice had increased adiposity and extreme insulin sensitivity. Loss of adipocyte Jak2 augmented hepatic insulin sensitivity and conferred resistance to diet-induced metabolic stress without overt changes in circulating fatty acids. While GH injections induced hepatic insulin resistance in control mice, the diabetogenic action was absent in JAK2A mice. Adipocyte GH signaling directly impinged on both adipose and hepatic insulin signal transduction. Collectively, our results show that adipose tissue governs the effects of GH on insulin and glucose homeostasis. Further, we show that JAK2 mediates liver insulin sensitivity via an extrahepatic, adipose tissue–dependent mechanism.

Authors

Kevin C. Corbit, João Paulo G. Camporez, Jennifer L. Tran, Camella G. Wilson, Dylan A. Lowe, Sarah M. Nordstrom, Kirthana Ganeshan, Rachel J. Perry, Gerald I. Shulman, Michael J. Jurczak, Ethan J. Weiss

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Figure 1

Loss of adipocyte Jak2 augments insulin responsiveness in chow-fed mice.

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Loss of adipocyte Jak2 augments insulin responsiveness in chow-fed mice....
(A) Total body weight and (B) fat mass in control (CON, black circles) and JAK2A mice (white circles). (C) Percentage body fat as a fraction of total body weight. (D) Total epididymal visceral and (E) inguinal subcutaneous fat. (F) Fasting blood glucose and (G) plasma insulin. (H) Insulin tolerance testing expressed as a percentage of basal (fasting) glucose in control (black circles) and JAK2A (white circles) mice. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by t test (B–F) and 1-way ANOVA (H). n = 7–11 for both cohorts. Data represent ± SEM.

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