Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle

Abstract

Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

Anti‐Diabetic, Anti‐Inflammatory, and Anti‐Oxidant Effects of Naringenin in an In Vitro Human Model and an In Vivo Murine Model of Gestational Diabetes Mellitus

“…A key strength of this study is the combined use of in vitro and in vivo models to investigate the ability of naringenin to disrupt pathways known to GDM pathophysiology. In vitro, TNF was used to recapitulate inflammation and impaired skeletal muscle glucose uptake associated with GDM pregnancies . It was found that naringenin treatment significantly improved insulin‐stimulated glucose uptake in human skeletal muscle compared to TNF treatment.…”

“…Insulin resistance is a central feature of GDM. There is extensive evidence to suggest that low‐grade maternal inflammation contributes to the peripheral insulin resistance characteristic of GDM . Several studies have demonstrated that pro‐inflammatory mediators, such as TNF, and pathogenic factors, such as bacterial and viral products, can induce defects within the insulin signaling pathway in skeletal muscle .…”

“…Tissue explants for placenta, VAT, and skeletal muscle were performed as previously described . Briefly, tissues were washed in PBS and blunt dissected to remove visible connective tissue, vessels, and calcium deposits.…”

“…Skeletal muscle explants were performed as detailed in Section and glucose uptake was performed as previously described (see Figure A for experimental flowchart) . Glucose uptake was performed on skeletal muscle obtained from six participants.…”

“…RNA was converted to cDNA using the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions. After the cDNA was diluted to 1.3 ng µL −1 in sterile milli‐Q water, qRT‐PCR was performed on the cDNA as previously described . The RT‐PCR was performed using the CFX384 Real‐Time PCR detection system (Bio‐Rad Laboratories, Gladesville, NSW, Australia) using 100 n m of pre‐designed and validated QuantiTect primers (primer sequences not available) (Qiagen; Chadstone Centre, VIC, Australia).…”