Abstract
Context and ObjectiveAdipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Design, Setting and ParticipantsAdipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.ResultsPioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm2 (p = 0.02) in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.ConclusionThe PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.
Highlights
Insulin resistance develops with obesity and in the setting of inadequate b-cell response, leads to type 2 diabetes (T2DM)
There were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold
A leading hypothesis behind these changes in adipose tissue is that increased adipocyte size in the setting of a relatively rigid extracellular matrix (ECM) leads to a compromised blood supply, adipocyte necrosis, inflammation, and fibrosis [5]
Summary
Insulin resistance develops with obesity and in the setting of inadequate b-cell response, leads to type 2 diabetes (T2DM). This process is complex, and many changes occur in the adipose tissue of insulin resistant subjects, including the development of a proinflammatory environment, characterized by an influx of macrophages, an alteration in collagen and other extracellular matrix (ECM) components, and hypoxia due to decreased capillaries [1,2,3,4]. TZDs improve peripheral insulin sensitivity, and have a spectrum of anti-inflammatory properties, including a reduction in plasma inflammatory markers, and a reduction in adipose tissue macrophages [6,7,8,9]. V-3 PUFA consumption resulted in an increase in adiponectin through a PPARc-dependent mechanism [13,14]
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