Abstract
Background/ObjectivesThe occurrence of chronic inflammation in visceral adipose tissue (VAT) in obese subjects precipitates the development of insulin resistance and type 2 diabetes (T2D). Anthocyanins and their main metabolite protocatechuic acid (PCA) have been demonstrated to stimulate insulin signaling in human adipocytes. The aim of this study was to investigate whether PCA is able to modulate insulin responsiveness and inflammation in VAT from obese (OB) and normal weight (NW) subjects.Subjects/MethodsVATs obtained from NW and OB subjects were incubated or not (control) with 100 μM PCA for 24 h. After incubation, tissues untreated and treated with PCA were acutely stimulated with insulin (20 nM, 20 min). PTP1B, p65 NF-κB, phospho-p65 NF-κB, IRS-1, IRβ, Akt, GLUT4 as well as basal and insulin-stimulated Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting in NW- and OB-VAT. Samples were assessed for PTP1B activity and adipocytokine secretion.ResultsPCA restored insulin-induced phosphorylation in OB-VAT by increasing phospho-Tyr-IRS-1 and phospho-Ser-Akt after insulin stimulation as observed in NW-VAT (p < 0.05). PTP1B activity was lower in OB-VAT treated with PCA with respect to untreated (p < 0.05). Compared to non-treated tissues, PCA reduced phospho-p65 NF-κB and IL-6 in OB-VAT, and IL-1β in NW-VAT (p < 0.05); and increased adiponectin secretion in NW-VAT (p < 0.05).ConclusionPCA restores the insulin responsiveness of OB-VAT by increasing IRS-1 and Akt phosphorylation which could be related with the lower PTP1B activity found in PCA-treated OB-VAT. Furthermore, PCA diminishes inflammation in VAT. These results support the beneficial role of an anthocyanin-rich diet against inflammation and insulin resistance in obesity.
Highlights
It is well recognized that obesity is highly associated with the onset of pathologies such as insulin resistance, type 2 diabetes mellitus (DM2), cardiovascular disease, and cancer [1]
OB-Visceral adipose tissue (VAT) showed different insulin signaling activation, inflammatory molecule expression, and protein tyrosine phosphatase 1B (PTP1B) activity compared to normal weight (NW) subjects
The results showed 52% and 43% reduction in IRS1 and GLUT4 protein levels, respectively, in VAT samples from OB individuals compared to NW tissues
Summary
It is well recognized that obesity is highly associated with the onset of pathologies such as insulin resistance, type 2 diabetes mellitus (DM2), cardiovascular disease, and cancer [1]. An important underlying cause of obesity-induced insulin resistance is chronic low-grade systemic inflammation which is originated predominantly in the visceral fraction of fat depot [2]. NF-κB [5, 6] which causes an increase in the gene expression of TNFα and IL-6, both implicated in the development of obesity-induced insulin resistance [4]. Insulin resistance is defined as the impairment of the insulin signaling, namely insulin receptor (IRβ)/IRS-1/PI3K/Akt pathway, in insulin-responsive cells such as adipocytes [7]. Protein phosphatases play an important role [8]. It is well recognized that protein tyrosine phosphatase 1B (PTP1B) attenuates insulin signaling transduction by removing Tyr phosphates from the activated insulin receptor and IRS-1 [9, 10]. Mice lacking PTP1B showed increased insulin sensitivity, suggesting that insulin signaling can be enhanced by PTP1B inhibition [11]
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