Efeitos da suplementação de curcumina nos parâmetros metabólicos, inflamatórios e na morfologia do tecido adiposo de mulheres com obesidade grave

Abstract

Introduction: Obesity is characterized by chronic low-grade inflammation resulting from adipose tissue dysfunction, and the phase of life at obesity onset is an important contributing factor. Curcumin, a bioactive compound with metabolic and anti-inflammatory properties, appears to act on adipocytes and macrophages, mitigating the deleterious effects of the disease; however, human studies remain limited. Therefore, understanding the factors that may influence adipose tissue remodeling in response to chronic positive energy balance, as well as the phase of life at obesity onset, is essential to better explain the metabolic variability observed among individuals with obesity. Objective: To evaluate the effect of curcumin supplementation on metabolic, inflammatory, and morphological parameters of subcutaneous and omental adipose tissue in women with severe obesity. Additionally, to analyze the association between the phase of life at obesity onset and current age with the morphology of these adipose depots. Methods: Women with severe obesity (BMI ≥ 40 kg/m²), aged 20 to 59 years, who were candidates for bariatric surgery, were recruited. Clinical, anthropometric, and biochemical assessments were performed before and after supplementation with 1,500 mg/day of curcumin (98.75% curcuminoids) or placebo (cornstarch). Clinical evaluation included age, comorbidities, phase of life at obesity onset, and current medications. Anthropometric assessment included weight, waist circumference (WC), hip circumference (HC), and neck circumference (NC), followed by calculation of the waist-to-hip ratio (WHR). Biochemical tests assessed glycemic and lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and high-sensitivity C-reactive protein (hs-CRP). Pro-inflammatory (PAI-1, leptin, TNF-α, IL-6) and antiinflammatory (adiponectin, IL-10) cytokines were analyzed using immunoenzymatic assays or multiplex technology. During bariatric surgery, the attending physician collected omental (OAT) and subcutaneous (SAT) adipose tissue biopsies, which were formalin-fixed and paraffinembedded. Histological slides were used to measure adipocyte area (hematoxylin-eosin) and total fibrosis percentage (picrosirius). Immunohistochemistry using CD68+ and perilipin-1 (PLIN-1) markers identified macrophages and cellular activity, respectively. For evaluation of the life stage of obesity development, participants were classified as Early (≤19 years) or Late (>19 years), and by current age as Younger (≥30 and <40 years) and Older (≥40 and <50 years). Statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS), version 21.0, with significance set at p<0.05. Results: Article 1: Twenty-four women participated, with a mean age of 34.33 years and BMI of 46.40 kg/m². Twelve-week curcumin supplementation reduced serum PAI-1 concentrations (p=0.015), with no differences in other glycemic, lipid, or inflammatory markers. Article 2: Eight women (mean age 34 years; BMI 48.04 kg/m²) underwent six months of supplementation prior to bariatric surgery, and their adipose tissues were compared. The curcumin group exhibited greater CLS density (p=0.045) and higher macrophage density in intravascular (p=0.023) and perivascular regions (p=0.021) of OAT. In SAT, greater macrophage density was identified within fibrotic areas (p=0.014). In addition to morphological changes, higher delta values for TG and VLDL-c were observed in women who received curcumin. Article 3: Thirty-four women participated (mean age 40.09 years; BMI 50.58 kg/m²). In OAT, greater macrophage density within fibrotic regions was observed in the “Late-Younger” group, and lower density in the “Early-Younger” group (p=0.005). Younger women presented a smaller omental adipocyte area (p=0.034). Unlike OAT, macrophages within fibrotic regions of SAT were influenced only by current age, with higher density in Younger women (p=0.000). Furthermore, only the life stage of obesity development influenced intravascular (p=0.004) and perivascular (p=0.029) macrophages in SAT. Conclusion: Our results demonstrate that twelve weeks of curcumin supplementation may exert cardioprotective effects in women with severe obesity, while prolonged supplementation may induce adipose tissue remodeling; however, further studies are needed to confirm whether such remodeling is beneficial. Moreover, the phase of life at obesity onset and current age may exert independent and combined effects that manifest differently in the morphology of omental and subcutaneous adipose tissues.