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Cited by 106Cardiovascular and exercise physiologyAdipose Tissue and MetabolismDiabetes, Cardiovascular Risks, and Lipoproteins

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Fat Oxidation, Fitness and Skeletal Muscle Expression of Oxidative/Lipid Metabolism Genes in South Asians: Implications for Insulin Resistance?

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Hall, Lesley M. L., Moran, Colin N., Milne, Gillian R., Wilson, John, MacFarlane, Niall G., Forouhi, Nita G., Hariharan, Narayanan, Salt, Ian P., Sattar, Naveed, Gill, Jason M. R.·2010·PLoS ONE
DOI 10.1371/journal.pone.0014197PMC PMC2995737
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Abstract

BACKGROUND: South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures. METHODOLOGY/PRINCIPAL FINDINGS: Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml x kg(-1) x min(-1), p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg x kg(-1) x min(-1) at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg x kg(-1) x min(-1) at 25 ml O(2) x kg(-1) x min(-1), p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10-13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity. CONCLUSIONS/SIGNIFICANCE: These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.

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Crossref · 10.1371/journal.pone.0014197

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Figure 1 Fat oxidation (A) and carbohydrate oxidation (B) during incremental submaximal exercise. Intensity expressed in terms of absolute oxygen uptake (i.e. ml.kg−1.min−1). P values shown are for the main-effect difference between European and South Asian groups, either unadjusted, or adjusted for age, BMI and fat mass.
Figure 1 Fat oxidation (A) and carbohydrate oxidation (B) during incremental submaximal exercise. Intensity expressed in terms of absolute oxygen uptake (i.e. ml.kg−1.min−1). P values shown are for the main-effect difference between European and South Asian groups, either unadjusted, or adjusted for age, BMI and fat mass.CC BY · PubMed Central
Figure 2 Fat oxidation (A) and carbohydrate oxidation (B) during incremental submaximal exercise. Intensity expressed relative to each individual's maximal oxygen uptake (i.e. percentage VO2max). P values shown are for the main-effect difference between European and South Asian groups, either unadjusted, or adjusted for age, BMI and fat mass.
Figure 2 Fat oxidation (A) and carbohydrate oxidation (B) during incremental submaximal exercise. Intensity expressed relative to each individual's maximal oxygen uptake (i.e. percentage VO2max). P values shown are for the main-effect difference between European and South Asian groups, either unadjusted, or adjusted for age, BMI and fat mass.CC BY · PubMed Central
Figure 3 Plasma insulin (A), glucose (B) and NEFA (C) responses to a 75 g oral glucose load. Summary measures of these responses are presented in Table 3.
Figure 3 Plasma insulin (A), glucose (B) and NEFA (C) responses to a 75 g oral glucose load. Summary measures of these responses are presented in Table 3.CC BY · PubMed Central
Figure 4 Individual insulin sensitivity index values for the European and South Asian men. Horizontal bars denote mean values. P values shown are for the difference between European and South Asian groups, either unadjusted, or adjusted for age, BMI and fat mass.
Figure 4 Individual insulin sensitivity index values for the European and South Asian men. Horizontal bars denote mean values. P values shown are for the difference between European and South Asian groups, either unadjusted, or adjusted for age, BMI and fat mass.CC BY · PubMed Central
Figure 5 Insulin signalling molecule expression in subjects. Soluble cytosolic (C) and microsomal (M) fractions were prepared from muscles incubated ex vivo in the presence or absence of insulin. Fractions were resolved by SDS-PAGE and subjected to immunoblotting with the antibodies indicated. Representative blots are shown from one South Asian and one European subject.
Figure 5 Insulin signalling molecule expression in subjects. Soluble cytosolic (C) and microsomal (M) fractions were prepared from muscles incubated ex vivo in the presence or absence of insulin. Fractions were resolved by SDS-PAGE and subjected to immunoblotting with the antibodies indicated. Representative blots are shown from one South Asian and one European subject.CC BY · PubMed Central
Figure 6 Relationship between exercise fat oxidation and insulin sensitivity index (A) and basal PKB Ser473 phosphoryation (B).
Figure 6 Relationship between exercise fat oxidation and insulin sensitivity index (A) and basal PKB Ser473 phosphoryation (B).CC BY · PubMed Central
Figure 7 Relationship between basal PKB Ser473 phosphoryation and insulin sensitivity index.
Figure 7 Relationship between basal PKB Ser473 phosphoryation and insulin sensitivity index.CC BY · PubMed Central
Figure 8 Relationships between exercise fat oxidation and skeletal muscle expression of oxidative and lipid metabolism genes. Significant correlations (p<0.05) are denoted by an asterix. P (int) signifies p-value for interaction in relationship between gene expression and fat oxidation during exercise between European and South Asian groups.
Figure 8 Relationships between exercise fat oxidation and skeletal muscle expression of oxidative and lipid metabolism genes. Significant correlations (p<0.05) are denoted by an asterix. P (int) signifies p-value for interaction in relationship between gene expression and fat oxidation during exercise between European and South Asian groups.CC BY · PubMed Central

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Research works printed but not linked: 1

  1. GJG Davey, 2000, Effects of exercise on insulin resistance in South Asians and Europeans., J Exerc Physiol, 3, 6

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Authors
Hall, L. M. L., Moran, C. N., Milne, G. R., Wilson, J., MacFarlane, N. G., Forouhi, N. G., Hariharan, N., Salt, I. P., Sattar, N., & Gill, J. M. R.
Affiliations
  • University of Glasgow (GB)
  • Addenbrooke's Hospital (GB)
  • Pfizer (United States) (US)
Corresponding author
Gill, Jason M. R.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-12-01
Volume
5
Issue
12
Pages
e14197
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0014197
PMC
PMC2995737
OpenAlex
W2071313377
Cited by
106
References
76
Citations by year
2026: 4 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 3 · 2013: 10 · 2012: 8
FWCI
16.27
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Stirling Online Research Repository (University of Stirling) (submittedVersion, cc-by)
Funders
  • Pfizer
  • Diabetes UK (06/0003224)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
South Asians, insulin resistance, fat oxidation, skeletal muscle gene expression, lipid metabolism genes, VO2max, exercise capacity, CPT1A, fatty acid synthase
MeSH terms
Adipose Tissue, Adult, Anthropometry, Asia, Biopsy, Body Composition, Fatty Acids, Female, Humans, Insulin, Insulin Resistance, Male, Oxygen, Signal Transduction, Body Mass Index, Muscle, Skeletal, Lipid Metabolism

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