An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women: Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants

Goedecke, Julia H.; Mendham, Amy E.; Clamp, Louise; Nankam, Pamela A. Nono; Smidt, Melony C Fortuin-de; Phiri, Lindokuhle; Micklesfield, Lisa K.; Keswell, Dheshnie; Woudberg, Nicholas J.; Lecour, Sandrine; Alhamud, Ali; Kaba, Mamadou; Lutomia, Faith M; Jaarsveld, Paul J van; Villiers, Anniza de; Kahn, Steven E.; Chorell, Elin; Hauksson, Jón; Olsson, Tommy

doi:10.2196/resprot.9098

Cited by 21 publications

(49 citation statements)

References 85 publications

(92 reference statements)

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“…Pulmonary gas exchange was measured by determining O 2 and CO 2 concentrations and ventilation to calculate VO 2 consumption using a metabolic gas analysis system (CPET, Cosmed, Rome Italy). A 2-point calibration was conducted prior to each test, as previously described 20 .…”

Section: -Week Interventionmentioning

confidence: 99%

“…Accordingly, investigators were blinded to the group allocation during pre-intervention testing, however, investigators were not blinded during post-intervention testing. Detailed information regarding recruitment, retention, analyses (CONSORT) and methods are reported in 20 . Ten participants dropped out of the study or were lost to follow-up.…”

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confidence: 99%

“…After a 4-6 h fast and at least 48-72 h after the last exercise session, fat samples were collected. Fat samples were obtained using a mini-liposuction technique 1,20 . Abdominal samples were from directly above the umbilicus, and gluteal samples were from the right upper outer quadrant.…”

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confidence: 99%

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Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

Mendham

Larsen

George

et al. 2020

Sci Rep

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We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (S i). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, S i (frequently sampled intravenous glucose tolerance test), body composition (dualenergy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre-and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H 2 o 2) production than aSAT (p < 0.05). Higher gSAT respiration was associated with higher gynoid fat (p < 0.05). Higher gSAt H 2 o 2 production and lower aSAT mitochondrial respiration were independently associated with lower S i (p < 0.05). In response to training, S i improved and gynoid fat decreased (p < 0.05), while H 2 o 2 production reduced in both depots, and mtDNA decreased in gSAT (p < 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p < 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots.

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Section: -Week Interventionmentioning

confidence: 99%

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confidence: 99%

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Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

Mendham

Larsen

George

et al. 2020

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“…Mitochondrial respiration capacity in human exercise intervention studies is not exclusive to skeletal muscle samples. Although such investigations are less common, different studies have measured respiration capacity in adipose tissue, 21,22 and blood cells (including lymphocytes and platelet). [23][24][25][26] Tests run in duplicates (or more) enable researchers to capture technical variability, and/or biological day-to-day variability within participants.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial respiration variability and simulations in human skeletal muscle: The Gene SMART study

et al. 2020

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Sarah Voisin and Nir Eynon are Co-senior authorship.Abbreviations: ATP, adenosine triphosphate; CI, complex I, electron input through CI; CV, coefficient of variation; CI P , oxidative phosphorylation (OXPHOS) capacity (P) through CI; ETS, electron transport system; CI+CII, convergent electron input through CI and CII CI+CII E , capacity (E) through CI+CII; CI+CII P , complex II (CII) linked respiration; E, ETS capacity; ETS, measurement of electron transport system; FCCP, p-trifluoromethoxyphenylhydrazone; Gene SMART, genes and skeletal muscle adaptive response to training; Inv-RCR, inverse of respiratory control ratio (CIL/CI+II P ); L, leak respiration; LCR, leak control ratio (CIL/CI+II E ); OXPHOS, oxidative phosphorylation; P, oxphos capacity; PCR, phosphorylation control ratio (CI+II P / CI+II E ); ROX, residual oxygen consumption; SCR, substrate control ratio at constant P (CIP/CI+II P ); TCA, tricarboxylic acid; TE M , technical error of measurement. AbstractMitochondrial respiration using the oxygraph-2k respirometer (Oroboros) is widely used to estimate mitochondrial capacity in human skeletal muscle. Here, we measured mitochondrial respiration variability, in a relatively large sample, and for the first time, using statistical simulations, we provide the sample size required to detect meaningful respiration changes following lifestyle intervention. Muscle biopsies were taken from healthy, young men from the Gene SMART cohort, at multiple time points. We utilized samples for each measurement with two technical repeats using two respirometer chambers (n = 160 pairs of same muscle after removal of low-quality samples). We measured the Technical Error of measurement (TE M ) and the coefficient of variation (CV) for each mitochondrial complex. There was a high correlation between measurements from the two chambers (R > 0.7 P < .001) for all complexes, but the TE M was large (7.9-27 pmol s −1 mg −1 ; complex dependent), and the CV was >15% for all complexes. We performed statistical simulations of a range of effect sizes at 80% power and found that 75 participants (with duplicate measurements) are required to detect a 6% change in mitochondrial respiration after an intervention, while for interventions with 11% effect size, ~24 participants are sufficient.The high variability in respiration suggests that the typical sample sizes in exercise studies may not be sufficient to capture exercise-induced changes. K E Y W O R D Sexercise, intervention, mitochondria, OXPHOS, oxygen consumption | 2979 JACQUES Et Al.

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“…as described previously [16]. Soleus and tibialis anterior intra-myocellular (IMCL) and extra-myocellular (EMCL) fat content were determined by magnetic resonance spectroscopy (MRS) using a point-resolved spectroscopy sequence with the following parameters: TR/TE 3000/33 ms, bandwidth 2000 Hz, 80 averages with voxel dimensions of 15×15×15 mm 3 .…”

Section: Introductionmentioning

confidence: 99%

β-cell function in black South African women: Associations with insulin clearance and ectopic fat

Smidt

Mendham

Hauksson

et al. 2020

Preprint

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Background: The role of ectopic fat, insulin secretion and clearance in the preservation of β-cell function in black African women with obesity who typically present with hyperinsulinemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of β-cell function), insulin secretion and clearance and ectopic fat deposition.Methods: This is a cross-sectional study of 43 black South African women (age 20-35 years) with obesity (BMI 30-40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently-sampled intravenous glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (aSAT) volume (magnetic resonance imaging), intramyocellular (IMCL) and extramyocellular fat content (EMCL) (magnetic resonance spectroscopy). Results: DI correlated positively with peripheral insulin clearance before (β 55.80, p=0.002) and after adjusting for hepatic insulin extraction. Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (p=0.033) and lower hepatic insulin extraction (p=0.022) associated with lower VAT, independent from SI, rather than with ectopic fat. Conclusion: Peripheral insulin clearance emerged as an important correlate of DI, independent from hepatic insulin extraction. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, was associated with both lower insulin secretion and higher hepatic insulin extraction, independent from SI, and may provide a novel explanation of these findings in black South African women with obesity.

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An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women: Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants

Cited by 21 publications

References 85 publications

Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

Mitochondrial respiration variability and simulations in human skeletal muscle: The Gene SMART study

β-cell function in black South African women: Associations with insulin clearance and ectopic fat

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