Macrophage and adipocyte IGF 1 maintain adipose tissue homeostasis during metabolic stresses

HR Chang, HJ Kim, X Xu, AW Ferrante Jr - Obesity, 2016 - Wiley Online Library
HR Chang, HJ Kim, X Xu, AW Ferrante Jr
Obesity, 2016Wiley Online Library
Objective Insulin‐like growth factor‐1 (IGF1) regulates differentiation and growth of tissues
and reduces stress and injury. IGF1 also in a tissue‐specific manner modulates the
differentiation and lipid storage capacity of adipocytes in vitro, but its roles in adipose tissue
development and response to stress are not known. Methods To study IGF1 in vivo, the
cellular sources of adipose tissue Igf1 expression were identified and mice were generated
with targeted deletion in adipocytes and macrophages. The effects of adipocyte and …
Objective
Insulin‐like growth factor‐1 (IGF1) regulates differentiation and growth of tissues and reduces stress and injury. IGF1 also in a tissue‐specific manner modulates the differentiation and lipid storage capacity of adipocytes in vitro, but its roles in adipose tissue development and response to stress are not known.
Methods
To study IGF1 in vivo, the cellular sources of adipose tissue Igf1 expression were identified and mice were generated with targeted deletion in adipocytes and macrophages. The effects of adipocyte and macrophage deficiency of IGF1 on adipose tissue development and the response to chronic (high‐fat feeding) and acute (cold challenge) stress were studied.
Results
The expression of Igf1 by adipose tissue was derived from multiple cell types including adipocytes and macrophages. In lean animals, adipocytes were the primary source of IGF1, but in obesity expression by adipocytes was reduced and by macrophages increased, so as to maintain overall adipose tissue Igf1 expression. Genetic deletion studies revealed that adipocyte‐derived IGF1 regulated perigonadal but not subcutaneous adipose tissue mass during high‐fat feeding and the development of obesity. Conversely, macrophage‐derived IGF1 acutely modulated perigonadal adipose tissue mass during thermogenic challenges.
Conclusions
Local IGF1 is not required in lean adipose tissue development but is required to maintain homeostasis during both chronic and acute metabolic stresses.
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