The relationship between hot flashes and fatty acid binding protein 2 in postmenopausal women

Abstract

Introduction: Hot flashes, the most bothering symptom of menopause, are linked to a metabolic inflammation. Due to estrogen deficiency in menopause, dysbiosis is observed. The intestinal barrier affects the interaction of microbiota in healthy or unhealthy individuals. This study investigates the relationship between hot flashes and gut permeability in postmenopausal women.

Participants and design: In this cross-sectional study, we divided 289 women, aged 40-65 years, into four groups based on their hot-flash severity: HF0: never experienced hot flashes; HFm: mild hot flashes; HFM: moderate hot flashes; HFS: severe hot flashes. The measured variables included the clinical parameters; hot flashes experience; fasting plasma levels of zonulin, fatty acid binding protein 2 (FABP2), endotoxin, and cytokines/chemokines. We used multiple linear regression analysis to evaluate the relationship between hot flashes and the previously mentioned gut barrier proteins.

Settings: The study was performed in a hospital medical center.

Results: The hot flashes had a positive tendency toward increased levels of circulating FABP2 (P-trend = 0.001), endotoxin (P-trend = 0.031), high-sensitivity C-reactive protein (hs-CRP) (P-trend = 0.033), tumor necrosis factor alpha (TNF-α) (P-trend = 0.017), and interferon-inducible protein-10 (IP10) (P-trend = 0.021). Spearman's correlation analysis revealed significant correlations of FABP2 with endotoxin, TNF-α, monocyte chemoattractant protein-1, IP10, and hs-CRP in the 289 postmenopausal women included in this study. Linear regression analysis revealed that hot-flash severity had significant assoiciations with FABP2 (P-trend = 0.002), but not with zonulin. After adjusting for body mass index, age, and menopause duration, multivariate linear regression analysis revealed the differences between HFs (% difference (95% confidence interval), 22.36 (8.04, 38.59), P = 0.01) and HF0 groups in terms of FABP2 levels.

Conclusions: This study shows that hot flashes are significantly associated with FABP2 levels in postmenopausal women. It suggests that severe hot flashes are linked to an increase in intestinal barrier permeability and low-grade systemic inflammation.

Fig 1. Correlation between FABP2 and circulating inflammatory factors.

Correlations between FABP2 levels and endotoxin (A), TN-Fα (B), IP10 (C), and MCP-1 (D) as well as hs-CRP € and HDL cholesterol (F) in 289 postmenopausal women were determined using Spearman’s correlation analysis. FABP2: fatty acid binding protein 2; TNF-α: tumor necrosis factor alpha; IP10: interferon-inducible protein-10; MCP-1: monocyte chemoattractant protein-1 high-sensitivity C-reactive protein; HDL: high-density lipoprotein.

Fig 2. Correlation between zonulin and hs-CRP, glucose, and lipid profiles.

Correlations between zonulin levels and hs-CRP (A), fasting glucose (B), HbA1c (C), HDL cholesterol (D), and triglycerides (E) in 289 postmenopausal women were determined using Spearman’s correlation analysis. HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive protein; HbA1c: glycosylated hemoglobin.

Fig 3. Associations between circulating endotoxin and inflammatory factors.

Associations between circulating endotoxin levels and TNF-α (A), IP10 B), and MCP-1(C) in 289 postmenopausal women were determined using Spearman’s correlation analysis. TNF-α: tumor necrosis factor alpha; IP10: interferon-inducible protein-10; MCP-1: monocyte chemoattractant protein-1.