Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
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Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. / Fabbrini, Elisa; Magkos, Faidon; Mohammed, B Selma; Pietka, Terri; Abumrad, Nada A; Patterson, Bruce W; Okunade, Adewole; Klein, Samuel.
In: Proceedings of the National Academy of Science of the United States of America, Vol. 106, No. 36, 2009, p. 15430-15435.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
AU - Fabbrini, Elisa
AU - Magkos, Faidon
AU - Mohammed, B Selma
AU - Pietka, Terri
AU - Abumrad, Nada A
AU - Patterson, Bruce W
AU - Okunade, Adewole
AU - Klein, Samuel
N1 - (Ekstern)
PY - 2009
Y1 - 2009
N2 - Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic-hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDL-triglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower (P < 0.05), whereas skeletal muscle CD36 expression was higher (P < 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.
AB - Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic-hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDL-triglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower (P < 0.05), whereas skeletal muscle CD36 expression was higher (P < 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.
KW - Body Composition
KW - CD36 Antigens/metabolism
KW - DNA Primers
KW - Female
KW - Glucose/metabolism
KW - Glucose Clamp Technique
KW - Humans
KW - Intra-Abdominal Fat/metabolism
KW - Lipoproteins, VLDL/analysis
KW - Liver/chemistry
KW - Male
KW - Metabolic Diseases/etiology
KW - Obesity/complications
KW - Palmitates/metabolism
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Triglycerides/analysis
U2 - 10.1073/pnas.0904944106
DO - 10.1073/pnas.0904944106
M3 - Journal article
C2 - 19706383
VL - 106
SP - 15430
EP - 15435
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 36
ER -
ID: 290671132