Altered Subcutaneous Adipose Tissue Response to Systemic LPS Administration in Patients with Type 2 Diabetes

Mathur N

doi:10.4172/2155-6156.1000217

Abstract

Aim: Inflammation is thought to play a major role in impaired metabolism. However, the metabolic and inflammatory response of adipose tissue, to a pro-inflammatory stimulus is poorly defined in patients with Type 2 Diabetes Mellitus (T2DM). We therefore aimed to investigate whether adipose tissue in T2DM would display an altered response to E. coli LipoPolySaccharide (LPS). Materials and methods: Twelve patients with T2DM and 12 control subjects received an intravenous bolus injection of LPS (0.3 ng/kg). Abdominal subcutaneous adipose tissue biopsies, serum and plasma were obtained at 0, 2, 4, 6 and 8 hours after LPS. The gene expression of Tumour Necrosis Factor-α (TNF), InterLeukin-6 (IL-6), lipoprotein lipase (LPL), hormone sensitive lipase (HSL), fatty acid synthase (FASN), adiponectin and peroxisome proliferator-activated recptor γ (PPARγ) was analysed by real time reverse transcription Polymerase Chain Reaction (PCR). Results: The expression of TNF and IL-6 in adipose tissue increased after LPS administration without any difference between groups (2-way ANOVA, effect of time: p<0.001 and p=0.0001, respectively). In contrast, the expression of LPL, HSL and adiponectin in adipose tissue increased only in control subjects (2-way ANOVA, effect of time X group: p=0.03; p=0.02 and p=0.02, respectively). There was no effect of LPS on FASN or PPARγ in either group. Conclusion: Patients with T2DM demonstrate a resistance to LPS in terms of inducing important mediators of lipolysis and lipogenesis, although the expression of TNF and IL-6 in adipose tissue increased in both groups. And thus, adipose tissue may contribute to the acute inflammation-related metabolic complications seen in T2DM.

Highlights

Patients with Type 2 Diabetes Mellitus (T2DM) have an increased risk of infectious diseases and sepsis and the overall mortality due to infection is nearly twice as high when compared to non-diabetic patients [1]
Patients with T2DM demonstrate a resistance to LPS in terms of inducing important mediators of lipolysis and lipogenesis, the expression of Tumour Necrosis Factor-Alpha (TNF) and IL-6 in adipose tissue increased in both groups
Adipose tissue may contribute to the acute inflammation-related metabolic complications seen in T2DM

Summary

Introduction

Patients with T2DM have an increased risk of infectious diseases and sepsis and the overall mortality due to infection is nearly twice as high when compared to non-diabetic patients [1]. We have previously characterised the inflammatory response in plasma and skeletal muscle of patients with T2DM to a low-dose bolus of E. coli LipoPolySaccharide (LPS), a human-experimental model of systemic inflammation [2,3]. When compared to control subjects with Normal Glucose Tolerance (NGT), patients with T2DM exhibit attenuated Tumour Necrosis Factor-Alpha (TNF) and InterLeukin (IL)-6 responses. The phosphorylation of Adenosine Monophosphate-Activated Protein Kinase (AMPK), a major player in the regulation of cellular glucose uptake, was increased in the NGT group, but not in T2DM patients [3]. Compared to control subject’s patients with T2DM may have both an impaired ability to respond to pathogen-associated molecular patterns, such as LPS, and be more prone to develop dysregulated glucose disposal in the context of systemic inflammation [3]

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