Effect of Age and Weight Loss on Inflammation and Iron Homeostasis (HEP)

Effect of Age and Weight Loss on Obesity-related Inflammation and Iron Homeostasis in Women

The purpose of this study is to evaluate the effect of aging and weight loss on iron status and immune response in obese women. Iron deficiency and immune impairment are two of the numerous complications of obesity. The central hypothesis is that obesity-induced inflammation causes lower iron status through decreased iron absorption and availability in young and older obese women. Furthermore, the investigators hypothesize that this can be corrected with weight loss in both young and older obese women.

Study Overview

• Status: Completed
• Conditions: Obesity; Aging
• Intervention / Treatment: Other: Calorie Restriction

Detailed Description

Obese individuals have chronic inflammation, higher risk of iron deficiency, and impaired immune response. These are conditions seen also with aging, but it is unknown to what extent they may be further impacted by obesity in the elderly. With this study the investigators aim to establish the mechanism by which weight loss may reduce inflammation and enhance iron status in young and older obese adults through the peptide hormone hepcidin, which regulates iron homeostasis. The investigators also aim to identify a possible link between iron homeostasis and immune response through hepcidin, which has been implicated in T cell mediated immunity. The investigators hypothesize that obesity-induced inflammation causes dysregulation of hepcidin expression leading to lower iron status through decreased iron absorption and availability in young and older adults. Furthermore, the investigators hypothesize that hepcidin dysregulation, and thus iron status can be mitigated with weight loss in both young and older obese adults. This hypothesis will be tested in obese young and older women undergoing weight loss through calorie restriction. Change in iron status, inflammation, and hepcidin will be determined before and after weight loss. Further, the impact of inflammatory environment of obesity on peripheral blood mononuclear cell hepcidin, ferroportin, intracellular iron, and T cell function in young and older adults will be determined. This study will address two important public health problems, i.e. obesity and iron deficiency and will be an important step toward the identification of strategies to enhance health of obese young and older adults.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • JM USDA Human Nutrition Research Center on Aging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Enrolling patients in the Weight and Wellness Center (WWC) at Tufts Medical Center, part of their Tufts Employees, low calorie diet (LCD) or pre-surgical low calorie diet (PS-LCD) program, or enrolling at WWC as individual patients.
• BMI in the range of 30 to 55 kg/m2.
• Either ages 18-45 or >60.

Exclusion Criteria:

• Pregnancy.
• Weight reduction greater than or equal to 3% in the past 3 months.
• Prior gastric restrictive surgery.
• Weight loss medications within the 4 weeks prior to screening.
• History of eating disorder.
• Renal disease (serum creatinine >2mg/dl).
• Hepatic disease, except for nonalcoholic steatohepatitis (NASH).
• Celiac disease, or any kind of intestinal malabsorption disorders.
• Gastrointestinal cancer.
• Hereditary hemochromatosis, or any blood disorders.
• Chronic infectious or inflammatory disease.
• Use of immunosuppressants.
• Severe iron deficiency anemia (hemoglobin<8 g/dl) or other conditions that would prevent them from discontinuing iron supplement use.
• Unwilling to discontinue iron supplement intake. The dietary plan recommended by the WWC will include daily intake of iron that meets the iron RDA for the subject's gender and age group, therefore discontinuing iron supplement will not be harmful for the participants. Intake of other supplements will not be an exclusion criteria, as long as it stays constant throughout the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Young (18-45 years); Obese young women (18-45y) undergoing calorie restriction.	Other: Calorie Restriction; Intervention consists of a calorically restricted diet regime designed and administered at the Weight and Wellness Center at Tufts University
Experimental: Older (>60 years); Obese older women (>60y) undergoing calorie restriction.	Other: Calorie Restriction; Intervention consists of a calorically restricted diet regime designed and administered at the Weight and Wellness Center at Tufts University

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum hepcidin	The investigators will determine the change in hepcidin at baseline and after 12-16 weeks of calorie restriction.	Baseline and 12-16 weeks
Change in inflammation (CRP, IL-6)	The investigators will determine the change in inflammation at baseline and after 12-16 weeks of calorie restriction.	Baseline and 12-16 weeks
Change in iron status	The investigators will determine the change in iron status at baseline and after 12-16 weeks of calorie restriction.	Baseline and 12-16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PBMC intracellular iron content		Baseline and 12-16 weeks
Change in PBMC Hepcidin expression		Baseline and 12-16 weeks
Change in PBMC ferroportin expression		Baseline and 12-16 weeks
Change in PBMC subpopulations and proliferation	After stimulation with ConA, PHA and anti-CD3/CD28	Baseline and 12-16 weeks

Collaborators and Investigators

• Sponsor: Tufts University
• Investigators: Principal Investigator: Simin N Meydani, DVM, PhD, Tufts University

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: January 26, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Estimate): November 16, 2015
• Last Update Submitted That Met QC Criteria: November 12, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Body Weight Changes; Obesity; Inflammation; Weight Loss
• Other Study ID Numbers: 2765