Previous research has found that males and females respond differently to exercise training, particularly with respect to improvements in blood sugar control and immune system health. This is crucial since insulin resistance, which can lead to type 2 diabetes and other health problems, affects millions of Canadians. People with insulin resistance often have higher inflammation. Exercise is known to improve insulin resistance and reduce inflammation, but females seem to benefit less from exercise compared to men. The investigators believe this difference might be due to estrogen, a hormone that helps regulate blood sugar (in non-exercising conditions) and reduce inflammation. Females have higher estrogen levels, which might explain their ability to regulate resting blood sugar control and also immune function at rest. Our research will investigate how estrogen influences the acute and chronic effects of exercise males. The investigators will study how estrogen influence's the body's response to exercise, particularly in terms of reducing inflammation and improving blood sugar levels as well as immune function. Overweight and obese males will undergo 2 weeks of high intensity interval training while taking either an estrogen supplement or placebo. Prior to and following training males will undergo an assessment of maximal fitness (VO2max test) and an oral glucose tolerance test. Prior to and following the acute exercise test blood samples will be taken to determine the acute effects of exercise on immune cell function and inflammation. Prior to and during the oral glucose tolerance test participants will have blood samples taken to determine glucose handling and insulin sensitivity. They will also have a muscle biopsy taken prior to and 1h into the oral glucose tolerance test to determine the effects of estrogen supplementation on insulin signaling, mitochondrial content and function, fat metabolism and fat storage in skeletal muscle.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
24
2 weeks of high intensity interval training while either taking estrogen or placebo
University of Waterloo
Waterloo, Ontario, Canada
Glucose AUC
Glucose AUC determined from blood samples taken during a 2h oral glucose tolerance test
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Insulin resistance/sensitivity
at rest (HOMA-IR) and during a 2 h oral glucose tolerance test (Matsuda index)
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Markers of insulin signaling
Western blot of the following markers: AMPKα Thr172 \& total AMPKα; phosphorylated Akt Ser437 \& total Akt; phosphorylated TBC1D4 Thr642 \& total TBC1D4; phosphorylated TBC1D1 Ser237 \& total TBC1D; total GLUT4 in human skeletal muscle in the fasted and insulin stimulated state
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Membrane bound GLUT4
GLUT4 content at the membrane in the fasted and insulin stimulated state (determined via immunofluorescence)
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Peripheral blood mononuclear cells
determination of immune cell response to acute exercise
Time frame: Visit 2 (baseline) and Visit 10 (Day 14)
Plasma cytokines from isolated PBMCs
pro- and anti-inflammatory cytokine content will be determine using a cytokine array and commercially available kits
Time frame: Visit 2 (baseline) and Visit 10 (Day 14)
Mitochondrial content
determined using electron microscopy
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Mitochondrial respiration
skeletal muscle mitochondrial respiration determined using high-resolution respirometry
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
intramyocellular lipid (IMCL) content
total and subcellular location-specific content and storage characteristics
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
aerobic fitness (VO2max)
VO2max determined during a graded exercise test
Time frame: Visit 2 (baseline) and Visit 10 (Day 14)
Sex hormone concentrations
Serum estradiol measured using commercially available kits
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Serum hormone concentrations
Serum progesterone measured using commercially available kits
Time frame: Visit 3 (baseline) and Visit 11 (Day 16)
Sex hormone concentrations
Serum testosterone measured using commercially available kits
Time frame: Visit 3 (baseline) and Visit 11 (day 16)
Serum hormone concentrations
Serum growth hormone measured using commercially available kits prior to a maximal graded exercise test and immediately (t=0 min), 30 and 60 min after the graded exercise test.
Time frame: Visit 2 (baseline) and visit 10 (day 14)
Serum hormone concentrations
Serum glucagon measured using commercially available kits prior to a maximal graded exercise test and immediately (t=0 min), 30 and 60 min after the graded exercise test.
Time frame: Visit 2 (baseline) and visit 10 (Day 14)
Neurotransmitter concentration
Serum epinephrine concentration measured using a commercially available kit prior to a maximal graded exercise test and immediately (t=0 min), 30 and 60 min after the graded exercise test.
Time frame: Visit 2 (baseline) and Visit 10 (day 14)
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