Mechanism of Decreased Iron Absorption in Obesity: Controlling Adiposity-related Inflammation

In states of high hepcidin concentration, intestinal iron absorption (through enterocytes) and recycling of iron (through macrophages) is reduced. The extent to which non-heme iron is absorbed from the diet is influenced by the composition of the diet. Ascorbic acid is a potent enhancer of non-heme iron absorption. It's mechanism of action is luminal reduction of dietary ferric iron (Fe3+) to more soluble ferrous iron (Fe2+). A study in the inestigator's laboratory showed that the enhancing effect of ascorbic acid on non-heme iron absorption is reduced in overweight and obese individuals. Possible explanations for this fact are the different sites of action of ascorbic acid and serum hepcidin on the enterocytes in dietary iron absorption. Increased hepcidin reduces iron efflux into the circulation at the basolateral membrane of the enterocyte. Therefore the improved iron transport into enterocytes through ascorbic acid at the luminal side (via the divalent metal transporter (DMT)-1), by reducing Fe3+ to Fe2+ seems to be less successful. To improve iron absorption in obese subjects, an intervention at the basolateral membrane of the enterocyte would be needed.

Inclusion criteria

• normal-weight (BMI18.5-24.9kg/m2) or obesity (BMI 29-40kg/m2)
• pre-menopausal
• no chronic illness and no significant medical conditions that could influence iron or inflammatory status other than obesity
• no-smoking

Exclusion criteria

• Diagnosed chronic disease or gastrointestinal disorders
• Metabolic disorders (e.g. diabetes)
• Regular use of medication (except oral contraceptives)
• Subject on a weight loss diet or planning to start a weight loss diet during the duration of the study
• Pregnancy or lactation