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
SN - 0012-1797
VL - 56
SP - 1960
EP - 1968
JO - Diabetes
JF - Diabetes
IS - 8
ER -