Premium
Impact of the GH‐IGF Axis on Adipose Tissue and Obesity: Are there Benefits of Endocrine Defects
Author(s) -
Kopchick John
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00417
Subject(s) - growth hormone receptor , longevity , adipose tissue , endocrinology , medicine , biology , endocrine system , life span , obesity , receptor , short stature , hormone , growth hormone , genetics , evolutionary biology
Disruption of the mouse growth hormone receptor gene (GHR−/−) results in dwarf, obese, GH resistant mice that possess low levels of IGF‐1 and high levels of GH with intense insulin sensitivity. These mice are similar to humans with Laron Syndrome (LS) in which the individuals are small in stature with low IGF‐1 and high GH levels. Cancer and diabetes rates in both the GHR−/− mice and LS individuals are low or non‐existent. In this regard, GHR−/− mice have extended longevity, in fact, they are the longest‐lived laboratory mouse. Thus, a defect in the action of GH may be beneficial for increased health‐span and longevity. In attempts to dissect which, if any, of the insulin sensitive tissue contribute to the extended health and lifespan of these mice, we have individually disrupted the GHR gene in liver, muscle, and adipose tissue. Surprisingly, only muscle specific GHR gene disruption resulted in a modest increase in life span while none of the others have the impressive extended longevity seen in GHR−/− mice. Since a decrease in the GH/IGF‐1 axis is important for extended health and lifespan, the ability to down regulate its action in adult life may be beneficial. To that end we have, and are, attempting to disrupt the mouse GHR in adult life. To date, disruption at 6 weeks of age results in female mice with extended longevity. Experiments to ‘knock‐out’ the GHR gene at 6 months and one year are ongoing. Also, since adipose tissue (AT) is metabolically important, data regarding the location and function of AT in these mice will be presented. Support or Funding Information This work was and supported by the State of Ohio’s Eminent Scholar Program that includes a gift by Milton and Lawrence Goll, the AMVETS, and NIH R01AG059779.