Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women

Abstract

Aims/hypothesis We have previously described differences in adipose cell size distribution and expression of genes related to adipocyte differentiation in subcutaneous abdominal fat obtained from insulin-sensitive (IS) and -resistant (IR) persons, matched for degree of moderate obesity. To determine whether other biological properties also differ between IR and IS obese individuals, we quantified markers of inflammatory activity in adipose tissue from overweight IR and IS individuals. Methods Subcutaneous abdominal tissue was obtained from moderately obese women, divided into IR (n=14) and IS (n=19) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Inflammatory activity was assessed by comparing expression of nine relevant genes and by immunohistochemical quantification of CD45-and CD68-containing cells. Results SSPG concentrations were approximately threefold higher in IR than in IS individuals. Expression levels of CD68, EMR1, IL8, IL6 and MCP/CCL2 mRNAs were modestly but significantly increased (p < 0.05) in IR compared with IS participants. Results of immunohistochemical staining were consistent with gene expression data, demonstrating modest differences between IR and IS individuals. Crown-like structures, in which macrophages surround single adipocytes, were rarely seen in tissue from either subgroup. Conclusions/interpretation A modest increase in inflammatory activity was seen in subcutaneous adipose tissue from IR compared with equally obese IS individuals. Together with previous evidence of impaired adipose cell differentiation in IR vs equally obese individuals, it appears that at least two biological processes in subcutaneous adipose tissue characterize the insulin-resistant state independent of obesity per se.Trial registration ClinicalTrials.gov NCT00285844

Adipose morphology and metabolic disease

“…These findings are consistent with independent reports of reduced adipogenesis in insulinresistant patients (Goedecke et al, 2011;Yang et al, 2004). Furthermore, these expression changes were also associated with modest increases in inflammatory activity in insulin-resistant AT (McLaughlin et al, 2008). As the presence of small adipocytes in both VAT and SAT appears to be correlated with increased hypertrophy of larger adipocytes in abdominal SAT (Liu et al, 2009), these findings could be interpreted as suggesting that SAT is the primary site for lipid accumulation; however, once a maximal SAT adipocyte size is reached, hyperplastic growth is initiated in both VAT and SAT.…”

Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat

“…Data on ATM gene expression in the context of the metabolic complications of obesity are limited. Expression of five inflammatory genes in SAT was shown to be different between insulinresistant and insulin-sensitive overweight patients [25]. In our study, we found significantly increased mRNA levels of 24 ATM-specific markers in the metabolic syndrome patients compared with all other groups in both fat depots.…”

“…While these data could not be obtained due to the modest amount of adipose tissue material, it would have been interesting to correlate these variables with gene expression data of ATM-specific markers. In fact, it has been shown that an increased proportion of small adipose cells is associated with inflammation in SAT [25]. In addition, because various subpopulations of macrophages may exist and express distinct surface markers depending on the local microenvironment, different ATM markers could be identified in different macrophage subpopulations of adipose tissue.…”

“…Accordingly, recent data suggest that human adipose tissue macrophages (ATM) show a complex phenotype and are not strictly polarised into M1 and M2 [22,23]. Several studies have examined expression levels of a few ATM genes in different groups of individuals [12,13,16,[24][25][26]. Given the interplay of biological systems, it is evident that reliance on a single or a few markers should be replaced by a spectrum of specific markers for study of ATM [1].…”

Guidelines for the Prevention of Stroke in Women

“…One proposed mechanism is that obesity is associated with a prothrombotic and proinflammatory state. [328][329][330][331][332] BMI is directly associated with fibrinogen, factor VII, plasminogen activator inhibitor, and tissue-type plasminogen activator antigen levels in both men and women. 328 Similar associations are present between abdominal obesity and hemostatic factors.…”