Influence of Body Weight and Composition on Immune Recovery
Influence of Body Weight and Composition on Immune Recovery
Immune dysfunction in individuals with obesity, secondary to chronic inflammation, may have
 an acute impact on War fighter health and readiness, and subsequent lethality. Indeed, ~51%
 of military personnel ages 17 or older are overweight, and ~15% have obesity (ranging from
 6.4% in the Marine Corps to 18.0% in the Army). In conjunction with in vitro functional tests
 to assess systemic immune function, the suction blister model is a minimally invasive
 procedure that allows in vivo assessment of immune function (i.e., skin barrier restoration),
 and related mechanisms (i.e., pro- and anti-inflammatory cytokine responses at the wound site
 during the early phases of wound healing), consequent to obesity. We have demonstrated that
 the blister wound model reliably assesses skin barrier restoration and immune function at the
 wound site; and that relatively modest sleep disruption degrades immune response at the site
 of the disrupted skin barrier and delays the initial restoration of the skin barrier.
 However, our prior work excluded participants with obesity (≥30 kg/m2), since obesity is
 associated with an altered inflammatory response which may subsequently impact the body's
 functional response to a skin wound. Prior studies have indicated that immune function and
 wound healing is perturbed in individuals with obesity versus those without obesity. Existing
 research mainly relied on blood biomarkers and in vitro tests to assess systemic immune
 function; however, incorporating the blister wound model permits evaluation of the functional
 immune response to obesity in addition to local immune response at the wound site. Further,
 military personnel with obesity may be more physically active than civilians with obesity,
 which could mitigate the effects of obesity on immune dysfunction. Therefore, the primary aim
 of this parallel-group study is to utilize a suction blister model and in vitro functional
 assays to examine differences in immune function between participants without obesity (BMI
 18.5-24.9 kg/m2) and with obesity (BMI ≥ 30 kg/m2) and related mechanisms (e.g., local
 cytokine response at the wound site and circulating markers of inflammation). Research will
 be conducted in a laboratory environment using males and females with obesity (BMI ≥ 30
 kg/m2) compared to normal weight (BMI 18.5-24.9 kg/m2) controls. Participants in the study
 described herein (n = 50; n = 25 with obesity and n = 25 lean) will undergo baseline testing
 and a period of dietary surveillance prior to induction of up to eight blisters via suction
 on participant's forearm, after which time the top layer of blisters will be removed to
 reveal the dermal layer of skin. The primary outcome measure is initial restoration of the
 skin barrier (via transepidermal water loss) and additional outcome measures include immune
 function (e.g., circulating markers of inflammation, cytokines at the blister site, and
 secretory immunoglobin) and nutrient status. Additionally, to assess the impact of BMI on
 skeletal muscle inflammation, a subset of volunteers (n = 12 with obesity and n =12 lean)
 will undergo a single muscle biopsy at the conclusion of skin barrier restoration. Findings
 from this study will determine if obesity affects the early phases of wound healing and
 whether further study is warranted, e.g., do stressors exacerbate immune decrements observed
 in obese individuals, or can nutrition counter-measures mitigate immune decrements given that
 micronutrient deficiency is common in individuals with obesity.
See brief summary above.
Inclusion Criteria:

 -  Are between the ages of 18 (or 17 for military personnel) and 39 (i.e., consistent
 with the age range of 95% of Active Duty enlisted and 75% of Active Duty officers)

 -  Have a Body Mass Index (BMI) in the range of 18.5 to <25 kg/m2 and have a percent body
 fat by circumference measurements that meets the Army's max allowable body fat
 standards for individuals classified as "without obesity"; or have a BMI ≥ 30 kg/m2
 and have a percent body fat by circumference measurements that exceeds the Army's max
 allowable body fat standards for individuals classified as "with obesity" (40).

 -  Have been weight stable (+/- 5 lbs.) for the past two months (not including temporary
 body weight fluctuations due to menstrual cycle) and agree not to attempt to lose or
 gain weight for the duration of the study;

 -  Participate in 120-300 mins of aerobic exercise over the course of at least 3 days per
 week as indicated by self-report data and confirmed during the study via actigraphy
 (i.e., consistent with the self-reported exercise habits of a majority of active duty
 military personnel) (1, 41)

 -  Are willing to participate in all study procedures and comply with all study
 instruction.

 -  Females must have normal menstrual cycles between 26-32 days in duration; 5 menstrual
 cycles within the past 6 months; or able to provide documentation of oral/hormonal
 contraceptive use which contains low-dose estrogen/progesterone to maintain continuous
 levels throughout the 28-day cycle (i.e., no placebos)

 -  Pass a general medical clearance.

 Exclusion Criteria:

 -  have a tattoo on both forearms that obscures the forearms and doesn't allow space for
 the suction blister induction;

 -  experienced more than a ~5 lbs. weight gain or loss in the last month than is not
 transient (e.g., menstrual).

 -  participate in more than 300 minutes of aerobic exercise per week as indicated by
 self-report data and confirmed during the study via actigraphy (i.e., consistent with
 self-reported exercise habits of ~20% of active duty military personnel) (1, 41).

 -  are habitually taking nonsteroidal anti-inflammatory drugs (e.g., Advil), aspirin,
 lipid-lowering drugs, corticosteroids or immunosuppressants (e.g. Humira);

 -  are immune-compromised (e.g., chemotherapy or radiation treatment);

 -  are suffering from an autoimmune disease (e.g., lupus);

 -  recovering from a surgery within the past 6 months;

 -  Current doctor-diagnosed and/or treated diabetes, hypertension or dyslipidemia

 -  are suffering from sleep apnea;

 -  smoke, dip, chew or vape tobacco or nicotine-containing products.

 -  regularly (more than 2 days per week) sleep less than 7 hours or more than 9 hours per
 night; or, take a nap 3 or more days per week.

 -  Pregnant or lactating

 -  problems with blood clotting (in the subset of participants receiving muscle biopsies
 only)

 -  allergy to lidocaine (in the subset of participants receiving biopsies only)

 Females Only:

 • Have abnormal menstrual cycles (not between 26-32 days in duration; or not 5-6 menstrual
 cycles within the past 6 month) or those that have had an intrauterine device (IUD) placed
 with the last month or removed within the past 3 months.