Targeted loss of ghr signaling in mouse skeletal muscle protects against high-fat diet-induced metabolic deterioration

Archana Vijayakumar, YingJie Wu, Hui (Herb) Sun, Xiaosong Li, Zuha Jeddy, Chengyu Liu, Gary J. Schwartz, Shoshana Yakar, Derek LeRoith

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Growth hormone (GH) exerts diverse tissue-specific metabolic effects that are not revealed by global alteration of GH action. To study the direct metabolic effects of GH in the muscle, we specifically inactivated the growth hormone receptor (ghr) gene in postnatal mouse skeletal muscle using the Cre/loxP system (mGHRKO model). The metabolic state of the mGHRKO mice was characterized under lean and obese states. High-fat diet feeding in the mGHRKO mice was associated with reduced adiposity, improved insulin sensitivity, lower systemic inflammation, decreased muscle and hepatic triglyceride content, and greater energy expenditure compared with control mice. The obese mGHRKO mice also had an increased respiratory exchange ratio, suggesting increased carbohydrate utilization. GH-regulated suppressor of cytokine signaling-2 (socs2) expression was decreased in obese mGHRKO mice. Interestingly, muscles of both lean and obese mGHRKO mice demonstrated a higher interleukin-15 and lower myostatin expression relative to controls, indicating a possible mechanism whereby GHR signaling in muscle could affect liver and adipose tissue function. Thus, our study implicates skeletal muscle GHR signaling in mediating insulin resistance in obesity and, more importantly, reveals a novel role of muscle GHR signaling in facilitating cross-talk between muscle and other metabolic tissues.

Original languageEnglish (US)
Pages (from-to)94-103
Number of pages10
JournalDiabetes
Volume61
Issue number1
DOIs
StatePublished - Jan 2012

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Somatotropin Receptors
High Fat Diet
Skeletal Muscle
Obese Mice
Muscles
Growth Hormone
Insulin Resistance
Myostatin
Interleukin-15
Liver
Adiposity
Energy Metabolism
Adipose Tissue
Triglycerides
Obesity
Carbohydrates
Cytokines
Inflammation
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Targeted loss of ghr signaling in mouse skeletal muscle protects against high-fat diet-induced metabolic deterioration. / Vijayakumar, Archana; Wu, YingJie; Sun, Hui (Herb); Li, Xiaosong; Jeddy, Zuha; Liu, Chengyu; Schwartz, Gary J.; Yakar, Shoshana; LeRoith, Derek.

In: Diabetes, Vol. 61, No. 1, 01.2012, p. 94-103.

Research output: Contribution to journalArticle

Vijayakumar, Archana ; Wu, YingJie ; Sun, Hui (Herb) ; Li, Xiaosong ; Jeddy, Zuha ; Liu, Chengyu ; Schwartz, Gary J. ; Yakar, Shoshana ; LeRoith, Derek. / Targeted loss of ghr signaling in mouse skeletal muscle protects against high-fat diet-induced metabolic deterioration. In: Diabetes. 2012 ; Vol. 61, No. 1. pp. 94-103.
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