Impact of Long-Term HFD Intake on the Peripheral and Central IGF System in Male and Female Mice

Abstract

The insulin-like growth factor (IGF) system is responsible for growth, but also affects metabolism and brain function throughout life. New IGF family members (i.e., pappalysins and stanniocalcins) control the availability/activity of IGFs and are implicated in growth. However, how diet and obesity modify this system has been poorly studied. We explored how intake of a high-fat diet (HFD) or commercial control diet (CCD) affects the IGF system in the circulation, visceral adipose tissue (VAT) and hypothalamus. Male and female C57/BL6J mice received HFD (60% fat, 5.1 kcal/g), CCD (10% fat, 3.7 kcal/g) or chow (3.1 % fat, 3.4 kcal/g) for 8 weeks. After 7 weeks of HFD intake, males had decreased glucose tolerance (p 0.01) and at sacrifice increased plasma insulin (p 0.05) and leptin (p 0.01). Circulating free IGF1 (p 0.001), total IGF1 (p 0.001), IGF2 (p 0.05) and IGFBP3 (p 0.01) were higher after HFD in both sexes, with CCD increasing IGFBP2 in males (p 0.001). In VAT, HFD reduced mRNA levels of IGF2 (p 0.05), PAPP-A (p 0.001) and stanniocalcin (STC)-1 (p 0.001) in males. HFD increased hypothalamic IGF1 (p 0.01), IGF2 (p 0.05) and IGFBP5 (p 0.01) mRNA levels, with these changes more apparent in females. Our results show that diet-induced changes in the IGF system are tissue-, sex- and diet-dependent.

Keywords

• IGF1
• IGF2
• IGFBP2
• high-fat diet
• obesity
• sex differences