Evaluating the evidence for macrophage presence in skeletal muscle and its relation to insulin resistance in obese mice and humans: a systematic review protocol

BMC Research Notes, Aug 2017

Objectives The current global rates of obesity and type 2 diabetes are staggering. In order to implement effective management strategies, it is imperative to understand the mechanisms of obesity-induced insulin resistance and diabetes. Macrophage infiltration and inflammation of the adipose tissue in obesity is a well-established paradigm, yet the role of macrophages in muscle inflammation, insulin resistance and diabetes is not adequately studied. In this systematic review, we will examine the evidence for the presence of macrophages in skeletal muscle of obese humans and mice, and will assess the association between muscle macrophages and insulin resistance. We will identify published studies that address muscle macrophage content and phenotype, and its association with insulin resistance. We will search MEDLINE/PubMed, EMBASE, and Web of Science for eligible studies. Grey literature will be searched in ProQuest. Quality assessment will be conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias Tool for animal studies. Results The findings of this systematic review will shed light on immune-metabolic crosstalk in obesity, and allow the consideration of targeted therapies to modulate muscle macrophages in the treatment and prevention of diabetes. The review will be published in a peer-reviewed journal and presented at conferences.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://link.springer.com/content/pdf/10.1186%2Fs13104-017-2686-6.pdf

Evaluating the evidence for macrophage presence in skeletal muscle and its relation to insulin resistance in obese mice and humans: a systematic review protocol

Bhatt et al. BMC Res Notes Evaluating the evidence for macrophage presence in skeletal muscle and its relation to insulin resistance in obese mice and humans: a systematic review protocol Meha Bhatt 2 3 Srikesh Rudrapatna 0 1 2 7 Laura Banfield 6 Rachel Bierbrier 0 2 7 PeiW‑en Wang 0 2 7 KuanW‑en Wang 0 2 7 Lehana Thabane 3 4 5 8 M. Constantine Samaan 0 1 2 3 7 0 Division of Pediatric Endocrinology, McMaster Children's Hospital , Hamilton, ON , Canada 1 Medical Sciences Graduate Program, McMaster University , Hamilton, ON , Canada 2 Department of Pediatrics, McMaster University , Hamilton, ON , Canada 3 Department of Health Research Methods , Evidence, and Impact , McMaster University , Hamilton, ON , Canada 4 Centre for Evalu‐ ation of Medicines , Hamilton, ON , Canada 5 Department of Anesthesia, McMaster University , Hamilton, ON , Canada 6 Health Sciences Library, McMaster University , Hamilton, ON , Canada 7 Division of Pediatric Endo‐ crinology, McMaster Children's Hospital , Hamilton, ON , Canada 8 Biostatistics Unit , St Joseph's Healthcare‐Hamilton, Hamilton, ON , Canada Objectives: The current global rates of obesity and type 2 diabetes are staggering. In order to implement effective management strategies, it is imperative to understand the mechanisms of obesity‑ induced insulin resistance and diabetes. Macrophage infiltration and inflammation of the adipose tissue in obesity is a well‑ established paradigm, yet the role of macrophages in muscle inflammation, insulin resistance and diabetes is not adequately studied. In this systematic review, we will examine the evidence for the presence of macrophages in skeletal muscle of obese humans and mice, and will assess the association between muscle macrophages and insulin resistance. We will identify published studies that address muscle macrophage content and phenotype, and its association with insulin resistance. We will search MEDLINE/PubMed, EMBASE, and Web of Science for eligible studies. Grey literature will be searched in ProQuest. Quality assessment will be conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias Tool for animal studies. Results: The findings of this systematic review will shed light on immune‑ metabolic crosstalk in obesity, and allow the consideration of targeted therapies to modulate muscle macrophages in the treatment and prevention of diabetes. The review will be published in a peer‑ reviewed journal and presented at conferences. Obesity; Type 2 diabetes; Insulin resistance; Immunometabolism; Macrophages; Skeletal muscle Introduction Type 2 diabetes (T2D) is a major health concern that is driven by the obesity epidemic [ 1 ]. As population growth and longevity rates continue to advance globally, obesitydriven disorders including cardiovascular disease, stroke and T2D represent an increasing burden on individuals, societies, and healthcare systems around the world [ 2 ]. Identifying the causes of obesity-driven T2D may pave the way for targeted interventions that treat, and ideally, prevent these diseases. The presence of obesity is known to trigger immune system activity and whole-body inflammation. This results in a low-grade, chronic inflammatory state characterized by the production of chemical attractants of immune cells called ‘chemokines’. Chemokines drive innate and adaptive immune cells to infiltrate the adipose tissue [ 3 ]. The sequence of immune cell involvement in obesity is complex. Early in the course of obesity, neutrophils enter the adipose tissue, followed by monocytes. Once monocytes sense the adipose tissue microenvironment, they differentiate to classically activated inflammatory (M1) macrophages that secrete pro-inflammatory cytokines, leading to adipose tissue inflammation and insulin resistance [ 3 ]. On the other hand, another type of macrophage, with anti-inflammatory actions, known as resident (M2) macrophage is also present in adipose tissue, and is responsible for retaining homeostasis by regulating tissue remodeling and function [ 4 ]. One theory linking the inflammatory responses in adipose tissue to muscle inflammation, and subsequent insulin resistance, suggests that there is a spillage of fatty acids and cytokines from expanding adipose tissue to the systemic vasculature. These cytokines and fatty acids are then able to elicit inflammation at distant organs including skeletal muscle and the liver [ 3 ]. Skeletal muscle plays a critical role in glucose homeostasis, and is prone to insulin resistance due to its sensitivity to lipotoxicity, glucotoxicity and inflammation. This might lead to the observed muscle insulin resistance, and eventual T2D [ 5 ]. While convincing evidence exists for the presence of macrophages and inflammation in obese adipose tissue [ 6 ], the substantiation of muscle inflammation leading to insulin resistance is less clear. Some studies have confirmed the presence of macrophages in muscle of mice [ 6–10 (...truncated)


This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1186%2Fs13104-017-2686-6.pdf

Meha Bhatt, Srikesh Rudrapatna, Laura Banfield, Rachel Bierbrier, Pei-Wen Wang, Kuan-Wen Wang, Lehana Thabane, M. Constantine Samaan. Evaluating the evidence for macrophage presence in skeletal muscle and its relation to insulin resistance in obese mice and humans: a systematic review protocol, BMC Research Notes, 2017, pp. 374, Volume 10, Issue 1, DOI: 10.1186/s13104-017-2686-6