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.

Sex Differences in Metabolic Recuperation After Weight Loss in High Fat Diet-Induced Obese Mice

“…Stanniocalcin (STC) 1 and 2 act as functional inhibitors of PAPP-A and PAPP-A2 blocking their proteolytic activity ( 27 , 28 ). However, in our previous studies we did not observe modifications in levels of circulating or hypothalamic pappalysins or stanniocalcins in response to a high fat diet (HFD) ( 10 , 11 ).…”

“…Both nutritional status and dietary intake modify metabolic hormones, such as insulin ( 7 ) and leptin ( 8 ), which then relay these signals to central control systems in attempt to maintain metabolic homeostasis. However, less is known regarding other factors such as the insulin-like growth factor (IGF) system that is also altered according to nutritional status and dietary intake ( 9 – 11 ).…”

“…We previously reported that both the central and peripheral IGF systems are affected by dietary intake in a time and sex-dependent manner ( 10 , 11 ). Here our objective was to determine whether peripheral and hypothalamic metabolic factors including the IGF system, are restored in HFD-induced obese C57BL/6J mice when weight-loss is induced by being placed on a normal chow diet.…”

Different dietary combinations of folic acid and vitamin B12 in parental diet results in epigenetic reprogramming of IGF2R and KCNQ1OT1 in placenta and fetal tissues in mice

“…H19/IGF2 locus is the most studied and is known to be influenced by dietary supplements. IGF2R, a maternally expressed gene that is another important and well‐known imprinting locus has an important role to play during development and is known to be influenced by dietary supplements (Guerra‐Cantera et al, 2020). KCNQ1OT1 is a paternally expressed lncRNA that lies on the same locus as that of H19/IGF2 and has also been associated with development (Koerner et al, 2009).…”

Exosomal miR-486-5p derived from human placental microvascular endothelial cells regulates proliferation and invasion of trophoblasts via targeting IGF1

“…Insulin-like growth factor 1 (IGF1) belongs to the IGF system, which is responsible for cell growth [19]. In addition, IGF1 is involved in multiple signaling pathways.…”