ESPE Abstracts (2019) 92 FC8.4

Peripheral and Hypothalamic Alterations in the Insulin-like Growth Factor (IGF) System in Response to High Fat Diet-induced Weight Gain

Santiago Guerra-Cantera1,2,3, Francisca Díaz1,3, Purificación Ros2,4, Alejandra Freire-Regatillo1,2,3, Marta Torrecilla-Parra 1,2, Vicente Barrios1,3, Laura Frago1,2,3, Julie A. Chowen1,3,5, Jesús Argente1,2,3,5


1Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain. 2Department of Pediatrics, Universidad Autónoma of Madrid, Marid, Spain. 3Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. 4Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain. 5 IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain


The insulin-like growth factor (IGF) system is fundamental for physiological processes such as growth and metabolism. In addition, in the brain it regulates glucose metabolism and neuroprotection. The IGF axis can be altered by nutritional status, but little is known regarding the effects of specific dietary components on this system.

Our aim was to examine how high-fat diet (HFD) and low-fat/high sucrose diet (LFHSD) intake affect the central and circulating IGF systems.

Male and female 7-week old C57/BL6J mice were fed a HFD (60% kcal from fat, 20% kcal from carbohydrates, 8.9% of weight from sucrose, 5.1 kcal/g), LFHSD (10% kcal from fat, 72% kcal from carbohydrates, 33.1% of weight from sucrose, 3.76 kcal/g) or standard rodent chow (3.1 % kcal from fat, 76% kcal from carbohydrates, 0.9% of weight from sucrose, 3.41 kcal/g) for 2 months. A glucose tolerance test (GTT) was performed a week before sacrifice. Plasma hormone levels were assayed by ELISA and relative gene expression by RT-PCR.

HFD increased weight gain and visceral and subcutaneous adipose tissue levels in both sexes (P<0.001) compared to chow and LFHSD. Energy intake was higher on the HFD in both sexes, reaching significance in females (P<0.001). Glucose tolerance was impaired only in males on the HFD (P<0.01). Plasma levels of free (P<0.001) and total (P<0.001) IGF1 were higher in HFD mice of both sexes, with HFD also increasing insulin (P<0.05) and IGFBP3 (P<0.01) levels. HOMA-IR was impaired by HFD in both sexes (P<0.05).

In the hypothalamus, IGF1 mRNA levels were increased after HFD consumption (P<0.05) in both sexes and by LFHSD only in females (P<0.05). Also in females, IGF2 (P<0.05) and IGFBP2 (P<0.01) mRNA were increased by HFD consumption compared to both chow and LFHSD. In all mice, relative IGF2 and IGFBP2 were positively correlated (r=0.843, P<0.001). In males, IGFBP5 mRNA levels increased in LFHSD and HFD compared to chow (P<0.01). No changes in other members of the IGF family were observed.

In conclusion, the central and peripheral IGF systems are modulated in HFD-induced weight gain, with this effect differing between males and females. In females, the HFD-induced increase in IGF2 and IGFBP2 expression in the hypothalamus, a glucose sensing region, deserves further investigation as these factors have been implicated in glucose metabolism and could possibly be involved in the increased ability of females to maintain a normal GTT even with a significantly increased body weight.