Increased capacity to maintain glucose homeostasis in a transgenic mouse expressing human but not mouse growth hormone with developing high-fat diet-related insulin resistance, hepatic steatosis and adipose dysfunction

in Journal of Molecular Endocrinology
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Yan Jin Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada

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Jessica S Jarmasz Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada

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https://orcid.org/0000-0002-3487-9610
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Shakila Sultana Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada

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Luis Cordero-Monroy Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Albrechtsen Research Centre, Winnipeg, Manitoba, Canada

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Carla G Taylor Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Albrechtsen Research Centre, Winnipeg, Manitoba, Canada
Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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Peter Zahradka Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Albrechtsen Research Centre, Winnipeg, Manitoba, Canada

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Elissavet Kardami Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada

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Peter A Cattini Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada

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https://orcid.org/0000-0002-1519-5475

Correspondence should be addressed to P A Cattini: Peter.Cattini@umanitoba.ca
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The objective was to assess the potential differential effects of human versus mouse growth hormone in vivo, given that human unlike mouse growth hormone can bind prolactin as well as the growth hormone receptor. To this end, a transgenic CD-1 mouse expressing human but not mouse growth hormone was generated, and the phenotypes of male mice fed with a regular chow or high-fat diet were assessed. Pancreas and epididymal white adipose tissue gene expression and/or related function were targeted as the pancreas responds to both prolactin and growth hormone receptor signaling, and catabolic effects like lipolytic activity are more directly attributable to growth hormone and growth hormone receptor signaling. The resulting human growth hormone-expressing mice are smaller than wild-type CD-1 mice, despite higher body fat and larger adipocytes, but both mouse types grow at the same rate with similar bone densities. Unlike wild-type mice, there was no significant delay in glucose clearance in human growth hormone-expressing mice when assessed at 8 versus 24 weeks on a high-fat diet. However, both mouse types showed signs of hepatic steatosis that correlated with elevated prolactin but not growth hormone RNA levels. The larger adipocytes in human growth hormone-expressing mice were associated with modified leptin (higher) and adiponectin (lower) RNA levels. Thus, while limited to observations in the male, the human growth hormone-expressing mice exhibit signs of growth hormone insufficiency and adipocyte dysfunction as well as an initial resistance to the negative effects of high-fat diet on glucose clearance.

 

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