Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity

Maria Kolak, Jukka Westerbacka, Vidya Velagapudi, Dick Wågsäter, Laxman Yetukuri, Janne Makkonen, Aila Rissanen, Anna-Maija Häkkinen, Monica Lindell, Robert Bergholm, Anders Hamsten, Per Eriksson, Rachel M. Fisher, Matej Orešič, Hannele Yki-Järvinen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

OBJECTIVE— We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity. RESEARCH DESIGN AND METHODS— A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 ± 0.3 vs. 14.4 ± 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations. RESULTS— Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator–activated receptor- and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group. CONCLUSIONS— Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.
Original languageEnglish
Pages (from-to)1960-1968
JournalDiabetes
Volume56
Issue number8
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

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Ceramides
Adipose Tissue
Obesity
Fats
Inflammation
Liver
Macrophages
Insulin Resistance
Triglycerides
Research Design
Adiponectin Receptors
Sphingomyelin Phosphodiesterase
Macrophage Inflammatory Proteins
Peroxisomes
Chemokine CCL2
Subcutaneous Fat
Plasminogen Activator Inhibitor 1
Crowns
Chemokines
Adipocytes

Cite this

Kolak, M., Westerbacka, J., Velagapudi, V., Wågsäter, D., Yetukuri, L., Makkonen, J., ... Yki-Järvinen, H. (2007). Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes, 56(8), 1960-1968. https://doi.org/10.2337/db07-0111
Kolak, Maria ; Westerbacka, Jukka ; Velagapudi, Vidya ; Wågsäter, Dick ; Yetukuri, Laxman ; Makkonen, Janne ; Rissanen, Aila ; Häkkinen, Anna-Maija ; Lindell, Monica ; Bergholm, Robert ; Hamsten, Anders ; Eriksson, Per ; Fisher, Rachel M. ; Orešič, Matej ; Yki-Järvinen, Hannele. / Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. In: Diabetes. 2007 ; Vol. 56, No. 8. pp. 1960-1968.
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title = "Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity",
abstract = "OBJECTIVE— We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity. RESEARCH DESIGN AND METHODS— A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 ± 0.3 vs. 14.4 ± 2.9{\%}). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations. RESULTS— Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator–activated receptor- and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group. CONCLUSIONS— Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.",
author = "Maria Kolak and Jukka Westerbacka and Vidya Velagapudi and Dick W{\aa}gs{\"a}ter and Laxman Yetukuri and Janne Makkonen and Aila Rissanen and Anna-Maija H{\"a}kkinen and Monica Lindell and Robert Bergholm and Anders Hamsten and Per Eriksson and Fisher, {Rachel M.} and Matej Orešič and Hannele Yki-J{\"a}rvinen",
year = "2007",
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Kolak, M, Westerbacka, J, Velagapudi, V, Wågsäter, D, Yetukuri, L, Makkonen, J, Rissanen, A, Häkkinen, A-M, Lindell, M, Bergholm, R, Hamsten, A, Eriksson, P, Fisher, RM, Orešič, M & Yki-Järvinen, H 2007, 'Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity', Diabetes, vol. 56, no. 8, pp. 1960-1968. https://doi.org/10.2337/db07-0111

Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. / Kolak, Maria; Westerbacka, Jukka; Velagapudi, Vidya; Wågsäter, Dick; Yetukuri, Laxman; Makkonen, Janne; Rissanen, Aila; Häkkinen, Anna-Maija; Lindell, Monica; Bergholm, Robert; Hamsten, Anders; Eriksson, Per; Fisher, Rachel M.; Orešič, Matej; Yki-Järvinen, Hannele (Corresponding Author).

In: Diabetes, Vol. 56, No. 8, 2007, p. 1960-1968.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity

AU - Kolak, Maria

AU - Westerbacka, Jukka

AU - Velagapudi, Vidya

AU - Wågsäter, Dick

AU - Yetukuri, Laxman

AU - Makkonen, Janne

AU - Rissanen, Aila

AU - Häkkinen, Anna-Maija

AU - Lindell, Monica

AU - Bergholm, Robert

AU - Hamsten, Anders

AU - Eriksson, Per

AU - Fisher, Rachel M.

AU - Orešič, Matej

AU - Yki-Järvinen, Hannele

PY - 2007

Y1 - 2007

N2 - OBJECTIVE— We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity. RESEARCH DESIGN AND METHODS— A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 ± 0.3 vs. 14.4 ± 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations. RESULTS— Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator–activated receptor- and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group. CONCLUSIONS— Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.

AB - OBJECTIVE— We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity. RESEARCH DESIGN AND METHODS— A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 ± 0.3 vs. 14.4 ± 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations. RESULTS— Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator–activated receptor- and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group. CONCLUSIONS— Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.

U2 - 10.2337/db07-0111

DO - 10.2337/db07-0111

M3 - Article

VL - 56

SP - 1960

EP - 1968

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 8

ER -