Iron Biology, Immunology, Aging, and Obesity: Four Fields Connected by the Small Peptide Hormone Hepcidin

Abstract

Iron status and immune response become impaired in situations that involve chronic inflammation, such as obesity or aging. Little is known, however, about the additional burden that obesity may place on the iron status and immune response in the elderly. This question is relevant given the rising numbers of elderly obese (BMI >30 kg/m 2 ) individuals and the high prevalence of iron deficiency worldwide. Iron is necessary for proper function of both the innate and adaptive immune system. Hepcidin, a peptide hormone that regulates cellular iron export, is essential for the maintenance of iron homeostasis. Therefore, since immune cells require iron for proper function hepcidin may also play an important role in immune response. In this review, we summarize the evidence for hepcidin as a link between the fields of gerontology, obesity, iron biology, and immunology. We also identify several gaps in knowledge and unanswered questions pertaining to iron homeostasis and immunity in obese populations. Finally, we review studies that have shown the impact of weight loss, focusing on calorie restriction, iron homeostasis, and immunity. These studies are important both in elucidating mechanistic links between obesity and health impairments and identifying possible approaches to target immune impairment and iron deficiency as comorbidities of obesity.

Micronutrient supplementation in gastric bypass surgery: prospective study on inflammation and iron metabolism in premenopausal women

“…This data was consistent with morbid obesity as described in others studies (2,18,19,36). A previous study has shown a correlation between hepcidin and ferritin values prior to surgery and a reduction of inflammation 6 months after surgery was associated with hepcidin and sTfR reductions (18).…”

“…Increased hepcidin concentrations in obesity have been linked to low-grade chronic inflammation and seems to contribute to reduced iron availability and mineral deficiencies in this condition (2,18,19). In this context, Tussing-Humphreys et al (18) observed that decreases of lowgrade inflammation and hepcidin levels improved iron metabolism 6 months after restrictive bariatric surgery in premenopausal women.…”

“…Obesity is associated with systemic low-grade chronic inflammation, which has been related to changes in iron metabolism (1)(2)(3)(4)(5). The inflammation condition is supported by increases in pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and from acute phase proteins, such as C-reactive protein (4,6).…”

“…Iron deficiency is the main cause of anemia after bariatric surgery, however, other micronutrient deficiencies (e.g., vitamin B12 and folic acid) can also influence iron metabolism (2,11,12,23). Bariatric surgery, especially RYGB surgery, induces a process of nutritional deficiencies that affect food intake and micronutrient absorption (23,24).…”

“…Bariatric surgery, especially RYGB surgery, induces a process of nutritional deficiencies that affect food intake and micronutrient absorption (23,24). With these conditions, micronutrient supplementation is indicated to maintain normalized iron levels and prevent anemia (2,11).…”