Serum leptin and adipocyte leptin mRNA levels decrease with dietary iron overload. (A) Iron levels measured by ferrozine-based colorimetric assay in mice fed low normal– and high-iron diet (n = 4 mice/group). (B) Tfrc mRNA levels quantified by qPCR and normalized to cyclophilin A in adipose tissue from mice fed different levels of dietary iron (n = 6 mice/group). (C) Serum leptin levels from the mice (n = 6 mice/group). (D) Intracellular leptin levels by Western blotting. Data are representative of 3 experiments with n = 4 per replicate. (E) Quantification of leptin protein levels from D normalized to tubulin (n = 4 mice/group). (F) Leptin mRNA levels quantified by qPCR and normalized to cyclophilin A in adipose tissue from mice fed different dietary iron (n = 6 mice/group). (G and H) Leptin expression is downregulated in live imaging (in vivo, G) and in tissue lysate (ex vivo, H) in high-iron–fed transgenic mice expressing the luciferase reporter gene under the control of leptin regulatory sequences. Data are representative of 3 experiments with n = 4 per replicate. *P < 0.05 and **P < 0.01 using 2-tailed Student’s t tests. Data represent mean ± SEM. Credit: https://www.jci.org/articles/view/81860/figure/2
Iron is the one mineral that humans can’t excrete, so the more iron that is consumed the greater the likelihood that leptin levels will drop, resulting in increased appetite and the potential to overeat. “We showed that the amount of food intake increased in animals that had high levels of dietary iron,” said Don McClain, M.D., Ph.D. “In people, high iron, even in the high-normal range, has been implicated as a contributing factor to many diseases, including diabetes, fatty liver disease and Alzheimer’s, so this is yet another reason not to eat so much red meat because the iron in red meat is more readily absorbed than iron from plants.”
In this study, male mice were fed high (2000 mg/kg) and low-normal (35 mg/kg) iron diets for 2 months, followed by measuring the levels of iron in fat tissue. They saw a 215% increase of iron in the mice fed a high iron diet as compared to the mice fed the low normal diet. In addition, leptin levels in blood were 42% lower in mice on the high iron diet compared to those on the low normal diet.
Results from the animal model were verified through ferritin blood tests from a large number of human participants in a previous clinical study. Ferritin blood tests measure the amount of iron stored in the body.
Fat tissue responds to iron availability to adjust the expression of leptin, a major regulator of appetite, energy expenditure and metabolism. “We don’t know yet what optimal iron tissue level is, but we are hoping to do a large clinical trial to determine if decreasing iron levels has any effect on weight and diabetes risk,” McClain said. “The better we understand how iron works in the body, the better chance we have of finding new pathways that may be targets for the prevention and treatment of diabetes and other diseases.” http://www.wakehealth.edu/News-Releases/2015/High_iron_intake_may_increase_appetite_disease_risk.htm
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