Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females

BACKGROUND: Fat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS. METHODS: The study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound. RESULTS: Metabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (β = -0.49; p = 0.001) and IGFBP-1 (β = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (β = -0.43; p = 0.004). CONCLUSIONS: The present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.