Plasma ferritin concentration is positively associated with in vivo fatty acid mobilization and insulin resistance in obese women

Abstract

High rates of fatty acid (FA) mobilization from adipose tissue are associated with insulin resistance (IR) in obesity. In vitro evidence suggests that iron stimulates lipolysis in adipocytes, but whether iron is related to in vivo FA mobilization is unknown. We hypothesized that plasma ferritin concentration ([ferritin]), a marker of body iron stores, would be positively associated with FA mobilization. We measured [ferritin], the rate of appearance of FA in the systemic circulation (FA Ra; stable isotope dilution), key adipose tissue lipolytic proteins and IR (hyperinsulinaemic-euglycaemic clamp) in 20 obese, premenopausal women. [Ferritin] was correlated with FA Ra (r = 0.65; P = 0.002) and IR (r = 0.57; P = 0.008); these relationships remained significant after controlling for body mass index and plasma [C-reactive protein] (a marker of systemic inflammation) in multiple regression analyses. We then stratified subjects into tertiles based on [ferritin] to compare subjects with 'High-ferritin' versus 'Low-ferritin'. Plasma [hepcidin] was more than fivefold greater (P < 0.05) in the High-ferritin versus Low-ferritin group, but there was no difference in plasma [C-reactive protein] between groups, indicating that the large difference in plasma [ferritin] reflects a difference in iron stores, not systemic inflammation. We found that FA Ra, adipose protein abundance of hormone-sensitive lipase and adipose triglyceride lipase, and IR were significantly greater in subjects with High-ferritin versus Low-ferritin (all P < 0.05). These data provide the first evidence linking iron and in vivo FA mobilization and suggest that elevated iron stores might contribute to IR in obesity by increasing systemic FA availability.

Plasma Phospholipids with Long‐Chain Polyunsaturated Fatty Acids and Dihydroceramides at the Crossroads of Iron Stores and Insulin Resistance

“…Leptin has shown to stimulate hepcidin, the main iron regulatory hormone, whereas associations between serum visfatin, an adipokine secreted mainly by visceral adipose tissue, and different iron metabolism parameters were observed in patients with obesity and T2DM . Recently, plasma ferritin concentration have been linked with in vivo fatty acid mobilization and IR in obese women . Iron stores reflected by serum ferritin may therefore play an important role in glucose metabolism disorders through their effects on lipid metabolism.…”

Association between Serum Ferritin and Blood Lipids: Influence of Diabetes and hs-CRP Levels

“…But the negative correlation between LDL-C and ferritin is influenced by diabetes frailly. This may be due to the role of ferritin in lipoprotein lipase activity, as described by Ryan et al [41]. At the same time, type 2 diabetes is closely related to lipase activity [13].…”

The Association Between Serum Ferritin Concentration and Visceral Adiposity Estimated by Whole-Body DXA Scan in Women With Polycystic Ovary Syndrome

“…In a recent meta-analysis, it has been shown that serum ferritin concentration is connected with fasting plasma glucose, serum insulin concentration (17), and plasma triglycerides (TG) level (18). Additionally, studies revealed that serum ferritin levels are connected with homeostasis model assessment of insulin resistance (HOMA-IR) in a non-diabetic population but not in patients with impaired glucose tolerance (19)(20)(21)(22). Therefore, serum ferritin has been proposed as an early marker of insulin resistance (21).…”