Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans

Effects of pioglitazone treatment

X. Xie, S. Sinha, Z. Yi, Paul R Langlais, M. Madan, B. P. Bowen, W. Willis, C. Meyer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background/Objectives:To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone.Subjects/Methods:Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment.Results:mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ∼55% and ∼4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone.Conclusions:Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalInternational Journal of Obesity
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2018
Externally publishedYes

Fingerprint

pioglitazone
Hyperlipidemias
Adipocytes
Insulin Resistance
Mitochondria
Inflammation
Glucose
Mitochondrial DNA
Lipid Metabolism
NADH Dehydrogenase
Cytoskeletal Proteins
Mitochondrial Proteins
Insulin
Triglycerides
Glucose Clamp Technique
Extracellular Matrix Proteins
PPAR gamma
Adiponectin
Adiposity
Organelle Biogenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans : Effects of pioglitazone treatment. / Xie, X.; Sinha, S.; Yi, Z.; Langlais, Paul R; Madan, M.; Bowen, B. P.; Willis, W.; Meyer, C.

In: International Journal of Obesity, Vol. 42, No. 2, 01.02.2018, p. 213-220.

Research output: Contribution to journalArticle

Xie, X. ; Sinha, S. ; Yi, Z. ; Langlais, Paul R ; Madan, M. ; Bowen, B. P. ; Willis, W. ; Meyer, C. / Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans : Effects of pioglitazone treatment. In: International Journal of Obesity. 2018 ; Vol. 42, No. 2. pp. 213-220.
@article{3898539ab0214ea79a4af54ad41d0299,
title = "Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: Effects of pioglitazone treatment",
abstract = "Background/Objectives:To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone.Subjects/Methods:Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment.Results:mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ∼55{\%} and ∼4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone.Conclusions:Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.",
author = "X. Xie and S. Sinha and Z. Yi and Langlais, {Paul R} and M. Madan and Bowen, {B. P.} and W. Willis and C. Meyer",
year = "2018",
month = "2",
day = "1",
doi = "10.1038/ijo.2017.192",
language = "English (US)",
volume = "42",
pages = "213--220",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans

T2 - Effects of pioglitazone treatment

AU - Xie, X.

AU - Sinha, S.

AU - Yi, Z.

AU - Langlais, Paul R

AU - Madan, M.

AU - Bowen, B. P.

AU - Willis, W.

AU - Meyer, C.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Background/Objectives:To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone.Subjects/Methods:Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment.Results:mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ∼55% and ∼4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone.Conclusions:Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.

AB - Background/Objectives:To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone.Subjects/Methods:Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment.Results:mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ∼55% and ∼4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone.Conclusions:Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.

UR - http://www.scopus.com/inward/record.url?scp=85041656058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041656058&partnerID=8YFLogxK

U2 - 10.1038/ijo.2017.192

DO - 10.1038/ijo.2017.192

M3 - Article

VL - 42

SP - 213

EP - 220

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 2

ER -