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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00948402.

Figures

Figure 1

Correlation between IGF-I zSDS (a and b) and IGFBP-1 (c and d), with HS score at ultrasound (US), and FM%. IGF-I zSDS, standard deviation score (SDS) of insulin-like growth factor-I levels according to age; IGFBP-1, IGF-binding protein-1; HS, hepatic steatosis; FM%, percentage of fat mass. The SDS of IGF-I levels were calculated according to age (zSDS). The classification of "bright liver" or HS was based on the following scale of hyperechogenicity: 0 = absent, 1 = light, 2 = moderate, 3 = severe, pointing out the difference between the densities of the liver and the right kidney. FM was determined by conventional bioelectrical impedance analysis and by bioelectrical impedance vector analysis with a single-frequency 50-kHz bioelectrical impedance analyzer.

Figure 2

Correlation between IGF-I/IGFBP-3 ratio with CRP (a), HS severity at ultrasound (US) (b), AST (c), and spleen longitudinal diameter (SLD) measured by postero-lateral scanning at US (d). IGF-I, insulin-like growth factor-I; IGFBP-3, IGF-binding protein-3; HS, hepatic steatosis, SLD, spleen longitudinal diameter. AST values were log transformed. SLD was measured by postero-lateral scanning. The maximum and cranio-caudal lengths were measured and then averaged.