Iron Metabolism Is Associated With Adipocyte Insulin Resistance and Plasma Adiponectin

Abstract

OBJECTIVEAdipocyte insulin resistance (IR) is a key feature early in the pathogenesis of type 2 diabetes mellitus (T2DM), and although scarce, data in the literature suggest a direct role for iron and iron metabolism–related factors in adipose tissue function and metabolism. Serum ferritin and transferrin were shown to be associated with muscle insulin resistance (IR) and T2DM, but little is known about the role of iron metabolism on adipose tissue. We therefore investigated whether markers of iron metabolism were associated with adipocyte IR and plasma adiponectin.RESEARCH DESIGN AND METHODSSerum ferritin, transferrin, total iron, non–transferrin-bound iron (NTBI), transferrin saturation, and plasma adiponectin were determined in 492 individuals. Adipocyte IR was defined by the product of fasting insulin and nonesterified fatty acids (NEFAs). Using linear regression analyses, we investigated the difference in adipocyte IR or adiponectin (in %) according to differences in iron metabolism markers.RESULTSSerum ferritin (β = 1.00% increase in adipocyte IR per 10 μg/L [95% CI 0.66–1.34]), transferrin (4.18% per 0.1 g/L [2.88–5.50]), total iron (1.36% per μmol/L [0.61–2.12]), and NTBI (5.14% per μmol/L [1.88–8.52]) were associated with adipocyte IR after adjustment for several covariates, including inflammatory markers. All markers of iron metabolism were also associated with NEFAs (all P < 0.01). In addition, ferritin and transferrin were inversely associated with adiponectin (both P < 0.01).CONCLUSIONSThe observed associations of several markers of iron metabolism with adipocyte IR and adiponectin suggest that factors related to iron and iron metabolism may contribute to adipocyte IR early in the pathogenesis of T2DM.

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

“…Contrary to our findings, a number of other studies have indicated a positive association between serum adiponectin and measures of human iron stores 9, 37, 38. These studies may be limited by the choice of surrogate for HIC.…”

“…These studies may be limited by the choice of surrogate for HIC. In those three studies, inverse correlations were noted between serum ferritin and serum adiponectin; however, this only reached statistical significance in two of the studies 9, 37. These are interesting observations that were not seen in our cohort.…”

Fine-tuned iron availability is essential to achieve optimal adipocyte differentiation and mitochondrial biogenesis

“…The association of iron overload with increased risk of type 2 diabetes mellitus has been extensively demonstrated in recent systematic reviews and meta-analysis [5][6][7][8]. Circulating markers of iron overload are also positively associated with visceral and subcutaneous fat depots [9] and with adipocyte insulin resistance [10]. A previous study using the 3T3-L1 mouse cell line suggested the importance of iron-related genes in adipocyte physiology [11].…”

Association of Low Serum Iron Levels with Low-grade Inflammation and Hyperadiponectinemia in Community-living Elderly Women

“…This finding is in accordance with the inverse association observed in the present study between the serum iron levels and the adiponectin levels independent of systemic inflammation in elderly women. However, two recent studies 30,31) demonstrated that adipocyte iron overload represses adiponectin transcription and the serum levels of adiponectin and that, consequently, the serum levels of ferritin and transferrin are inversely associated with those of adiponectin. Although we did not measure these variables, the latter finding is compatible with the current finding of an inverse association between the serum levels of iron and adiponectin.…”