Relation of depot-specific adipose inflammation to insulin resistance in human obesity

S J Bigornia,D T Hess,M M Mott,C M Apovian,N Gokce,M G Farb,L Joseph,A Fiscale,B Carmine

doi:10.1038/nutd.2012.3

Abstract

BACKGROUND:A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity.OBJECTIVE:To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat.METHODS:We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI⩾30 kg m−2) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS+ or CLS− based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLSs), omental (CLSo) and mesenteric (CLSm) adipose depots.RESULTS:The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS+) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS+ status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved.CONCLUSIONS:In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.

Highlights

Clinical studies consistently demonstrate a link between obesity and increased risk for developing insulin resistance[1] and type 2 diabetes (T2DM).[2]
Our primary objective was to determine whether the inflammatory status of subcutaneous fat as assessed by the presence of macrophage crown-like structures (CLS) relates to the state of inflammation in visceral fat
We examined whether CLSs, CLSo and CLSm status were associated with markers of insulin resistance and glycemic parameters in separate multivariable models using analysis of covariance (ANCOVA)

Summary

Introduction

Clinical studies consistently demonstrate a link between obesity and increased risk for developing insulin resistance[1] and type 2 diabetes (T2DM).[2]. 50% of adults) will be obese by 2030 leading to a major public health burden and cost.[5] While increased adiposity is associated with metabolic and cardiovascular risks, a growing body of evidence suggests that regional adiposity with selective accumulation of intra-abdominal visceral fat may be more closely linked to disease phenotypes than subcutaneous deposition.[6]. OBJECTIVE: To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat. The findings suggest that examination of subcutaneous regions that are more accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease

Objectives

Methods

Results