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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., (© 2015 The Obesity Society.)

Objective: The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin-sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied., Research Methods and Procedures: Adult female Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight (BW), a high-fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized to groups (n = 12) fed either low-fat or HF diets, with or without the TZD rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued, and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal (RP) adipose tissue morphology was determined from tissue collected by serial biopsies before and after 6 weeks of ROSI treatment and at sacrifice., Results: Measures of BW and adiposity did not differ among groups 6 weeks after stopping ROSI treatment. However, during treatment, ROSI in both diets significantly decreased RP adipocyte size and increased RP DNA content, and these effects continued to be observed after discontinuing treatment. ROSI administration also decreased circulating insulin, leptin, and triglycerides and increased circulating adiponectin levels; however, these effects were reversed on stopping treatment., Discussion: These results demonstrated that TZD-induced effects on adipocyte size and number were maintained after discontinuing treatment, even with consumption of an obesigenic diet. However, additional studies are needed to determine whether TZD-treated animals eventually achieve an adipocyte size similar to that of untreated animals at the expense of a higher BW.