Healthy, Insulin Sensitivity, Obesity, Women
Conditions
Keywords
Mitochondria, women, muscle, PBMC
Brief summary
The main goal of this project is to determine whether mitochondrial function in circulating cells is related to that measured in the muscle fibers of the same subjects.
Detailed description
Data from human and animal models strongly suggests that reduced tissue mitochondrial function can be an early marker for detection of dysfunctional metabolism. It is unclear if tissue mitochondrial dysfunction can be detected using less invasive methodology. In this project, the investigators plan to study mitochondrial bioenergetics in circulating cells and paired muscle biopsies in two metabolic disparate groups of women; healthy lean vs. overweight/obese with/without insulin resistant women of similar age. Women of similar age that are either healthy lean or overweight/obese with/without insulin resistance will be recruited to participate in one study that includes a blood draw and a muscle biopsy. Mitochondrial function in circulating blood cells and muscle tissue will be determined. The association between circulating blood cells and muscle tissue mitochondria respiration will be determined for the two groups combined, and differences between groups will also be investigated.
Interventions
None listed
Sponsors
Arkansas Children's Hospital Research Institute
University of Arkansas
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Women * 25-35 years of age * Either healthy lean (BMI\<25) or insulin resistant and obese (BMI \>30)
Exclusion criteria
* Medication that can affect study outcomes, as determined by the principal investigator, including anti-diabetic medication * Chronic diseases, acute inflammation, chronic renal failure (glomerular filtration rate \<45), or heart problems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mitochondrial Function in Circulating Cells and Muscle Tissue in Young Women | During the visit, approximately 0.5 days | Skeletal muscle (m.vastus lateralis) and peripheral blood mononuclear cell (PBMC) mitochondrial respiration were determined in response to substrate inhibitor coupling protocols using high resolution respirometry. From this, mitochondrial respiration in leak and coupled states, and reserve respiratory capacity were determined in mitochondria from skeletal muscle and from PBMCs. It was determined whether mitochondrial function in circulating cells is related to that measured in the muscle tissue of the same subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Lean Healthy lean women, 25-35 years | 17 |
| Overweight/Obese With/Without IR Overweight/obese with/without insulin resistant women, 25-35 years | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Healthy Lean | Overweight/Obese With/Without IR | Total |
|---|---|---|---|
| Age, Customized 25-35 years | 17 Participants | 18 Participants | 35 Participants |
| BMI | 22.4 kg/m^2 STANDARD_DEVIATION 1.4 | 35.6 kg/m^2 STANDARD_DEVIATION 7 | 29.2 kg/m^2 STANDARD_DEVIATION 8.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 12 Participants | 25 Participants |
| Region of Enrollment United States | 17 participants | 18 participants | 35 participants |
| Sex/Gender, Customized Female | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 18 |
| other Total, other adverse events | 0 / 17 | 0 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 18 |
Outcome results
Primary
Mitochondrial Function in Circulating Cells and Muscle Tissue in Young Women
Skeletal muscle (m.vastus lateralis) and peripheral blood mononuclear cell (PBMC) mitochondrial respiration were determined in response to substrate inhibitor coupling protocols using high resolution respirometry. From this, mitochondrial respiration in leak and coupled states, and reserve respiratory capacity were determined in mitochondria from skeletal muscle and from PBMCs. It was determined whether mitochondrial function in circulating cells is related to that measured in the muscle tissue of the same subjects.
Time frame: During the visit, approximately 0.5 days
Population: Out of the 35 enrolled, 32 participants had all samples (paired blood and muscle samples). Thus, they were their own controls, and for the main question about correlation between circulating cells and muscle mitochondrial respiration, samples were all analyzed together. This enabled comparison of circulating cells/muscle mitochondria respiration along a spectrum of BMIs and insulin resistance.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Lean | Mitochondrial Function in Circulating Cells and Muscle Tissue in Young Women | PBMC ATP linked respiration | 26.48 pmol O2/min per 400K cells | Standard Error 2.54 |
| Healthy Lean | Mitochondrial Function in Circulating Cells and Muscle Tissue in Young Women | PBMC max respiration | 120.04 pmol O2/min per 400K cells | Standard Error 11.88 |
| Overweight/Obese +/- IR | Mitochondrial Function in Circulating Cells and Muscle Tissue in Young Women | PBMC ATP linked respiration | 30.46 pmol O2/min per 400K cells | Standard Error 2.44 |
| Overweight/Obese +/- IR | Mitochondrial Function in Circulating Cells and Muscle Tissue in Young Women | PBMC max respiration | 140.43 pmol O2/min per 400K cells | Standard Error 14.3 |