The primary objective is to compare the effects of 12 weeks of resistance training to
endurance training with respect to whole-body and regional lipolytic (fat breakdown)
responses to acute walking exercise, (Aim 1), local adrenergic receptor blockade (Aim 2)
and in response to insulin during a hyperinsulinemic-euglycemic clamp (Aim 3). The
investigators will study the lipolytic response in the context of acute exercise,
whole-body fat oxidation and resting energy expenditure data. The investigators will
collect data on chronic lipogenesis (fat synthesis) and adipogenesis (fat cell
formation), as well as on ambulatory blood glucose control. Microdialysis techniques will
be utilized to determine the lipolytic rate in subcutaneous abdominal and gluteal adipose
tissue at rest, as well as during and after physical activity (walking) or during a
hyperinsulinemiceuglycemic clamp (including thigh muscle), before and after 12 weeks of
either resistance training or endurance training. To investigate the adrenergic
regulation of lipolysis before, during, and after exercise, a saline/ ethanol solution
will be perfused (to monitor blood flow) through three separate microdialysis probes in
subcutaneous abdominal and gluteal adipose tissue. The perfusate in the probes will
consist of either: 1) no additional substances (control probe) to address Aim 1; or 2)
phentolamine, an alpha adrenoreceptor blocker (treatment probe), and 3) propranolol, a
beta adrenoreceptor blocker (second treatment probe) to address Aim 2.
Hyperinsulinemic-euglycemic clamps will be performed to study the whole-body (with stable
isotope tracers) and regional (with microdialysis) antilipolytic effect of insulin, as
well as to measure insulin sensitivity with respect to glucose metabolism, before and
after the training programs for Aim 3. Immediately following the controlled laboratory
experiments, glycerol profiles (index of lipolysis) and glucose profiles (index of
glucose control) will continue to be monitored in the participant's free-living
environment over the ensuing 18 hours until the following morning. Additionally, at weeks
4 and 12 participants will come to the lab for adipose tissue biopsies of the abdominal
and gluteal adipose tissue for determination of adipogenesis and lipogenesis using
stable-isotope-labeled water they will drink daily over this eight-week labeling period.
Additional measures of fat oxidation as well as chronic and acute fat deposition will
allow interpretation of lipolysis in the context of fat oxidation and fat accumulation,
while 24-hour lipolysis and glucose profile measures will allow investigation of fat
metabolism and glucose control in a free-living condition. These studies will provide a
greater understanding of how these exercise modalities affect metabolism in women with
obesity and prediabetes, allowing practitioners to make more evidence based exercise
prescriptions intended to improve body composition, glycemic control, and weight
management.
The sample size for these studies will consist of 120 participants that will be randomly
assigned via computer randomization to either resistance training (n=60) or endurance
training (n=60) for 12 weeks. This sample size gives sufficient statistical power to
detect differences in lipolytic rate and other outcome variables, as determined by
previous studies examining similar outcome measures. A combination of stable tracers will
be infused into the bloodstream to examine various measures of fat metabolism under
resting and exercise conditions, as well as during a procedure that mimics a meal
(hyperinsulinemic-euglycemic clamp). However, these various tracers can interfere with
each other if studied altogether. Therefore these respective isotope tracer measures will
be run in only one-half of the participants from each Aim. 30 participants in the
endurance training group and 30 participants in the resistance training group will
complete Aims 1 and 2. A different 30 participants in the endurance training group and 30
in the resistance training group will complete Aim 3. Among the 60 participants (30 from
each exercise training group) completing Aims 1 and 2, there will be 15 individuals from
each exercise training group who will be randomized to undergo the tracer measures during
exercise while the other 15 from each exercise training group addressing Aims 1 and 2
will complete the exercise protocol without the tracer methods. These randomization
methods will also be applied to the 60 participants completing Aim 3, although these
participants will undergo a hyperinsulinemic-euglycemic clamp with or without the tracer
methods.
Participants will be recruited, screened, enrolled, and tested during months 4-55 of this
grant. Participant recruitment procedures and procurement of needed supplies will occur
during the first 3 months of the project. Additional recruitment, as well as screening
and testing of participants will occur at 1-2 per month over the ensuing 52 months. Two
microdialysis experiments will be performed on participants, one before and one after 12
weeks of exercise training, for a total of 240 microdialysis experiments. This plan will
therefore require 4-5 microdialysis tests per month on average during the testing months.
Stable label palmitate and glycerol isotope experiments will be conducted in 30 of the 60
participants undergoing the acute walking microdialysis experiments and in 30 of the 60
participants undergoing the clamp experiment. Deuterium water isotope experiments
(studies of lipogenesis and adipogenesis) will be conducted in 60 of the participants.