Measurement of intracellular triglyceride stores by 1H spectroscopy: Validation in vivo

Lidia S. Szczepaniak, Evelyn E. Babcock, Fritz Schick, Robert L. Dobbins, Abhimanyu Garg, Dennis K. Burns, J. Denis McGarry, Daniel T. Stein

Research output: Contribution to journalArticle

604 Citations (Scopus)

Abstract

We validate the use of 1H magnetic resonance spectroscopy (MRS) to quantitatively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two animal models of intracellular TG accumulation, intrahepatic and intramyocellular TG accumulation was confirmed histologically. Consistent with the histological changes, the methylene signal intensity at 1.4 ppm increased in both liver and muscle, whereas the signal at 1.6 ppm was unchanged. In response to induced fat accumulation, the TG concentration in liver derived from 1H MRS increased from 0 to 44.9 ± 13.2 μmol/g, and this was matched by increases measured biochemically (2.1 ± 1.1 to 46.1 ± 10.9 μmol/g). Supportive evidence that the methylene signal at 1.6 ppm in muscle is derived from investing interfacial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease characterized by absence of interfacial fat, no signal was detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An identical methylene chemical shift at 1.4 ppm was obtained in human subjects with fatty liver where the fat is located exclusively within hepatocytes. In experimental animals, there was a close correlation between hepatic TG content measured in vivo by 1H MRS and chemically by liver biopsy [R = 0.934; P < .0001; slope 0.98, confidence interval (CI) 0.70-1.17; y-intercept 0.26, CI -0.28 to 0.70]. When applied to human calf muscle, the coefficient of variation of the technique in measuring intramyocellular TG content was 11.8% in nonobese subjects and 7.9% in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5%, respectively. This study demonstrates for the first time that noninvasive in vivo 1H MRS measurement of intracellular TG, including that within myocytes, is feasible at 1.5-T field strengths and is comparable in accuracy to biochemical measurement. In addition, in mixed tissue such as muscle, the method is clearly advantageous in differentiating between TG from contaminating adipose tissue compared with intramyocellular lipids.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume276
Issue number5 39-5
StatePublished - May 1999

Fingerprint

Spectrum Analysis
Triglycerides
Spectroscopy
Magnetic resonance spectroscopy
Liver
Muscle
Magnetic Resonance Spectroscopy
Fats
Muscles
Tissue
Adipocytes
Adipose Tissue
Animals
Congenital Generalized Lipodystrophy
Confidence Intervals
Biopsy
Chemical shift
Fatty Liver
Muscle Cells
Protons

Keywords

  • Congenital generalized lipodystrophy
  • Dog
  • Fatty acid analysis
  • Human
  • Liver
  • Proton
  • Quantification
  • Rabbit
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

Cite this

Measurement of intracellular triglyceride stores by 1H spectroscopy : Validation in vivo. / Szczepaniak, Lidia S.; Babcock, Evelyn E.; Schick, Fritz; Dobbins, Robert L.; Garg, Abhimanyu; Burns, Dennis K.; McGarry, J. Denis; Stein, Daniel T.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 276, No. 5 39-5, 05.1999.

Research output: Contribution to journalArticle

Szczepaniak, Lidia S. ; Babcock, Evelyn E. ; Schick, Fritz ; Dobbins, Robert L. ; Garg, Abhimanyu ; Burns, Dennis K. ; McGarry, J. Denis ; Stein, Daniel T. / Measurement of intracellular triglyceride stores by 1H spectroscopy : Validation in vivo. In: American Journal of Physiology - Endocrinology and Metabolism. 1999 ; Vol. 276, No. 5 39-5.
@article{adb7e4d668394098ac52e7bdf55f2a85,
title = "Measurement of intracellular triglyceride stores by 1H spectroscopy: Validation in vivo",
abstract = "We validate the use of 1H magnetic resonance spectroscopy (MRS) to quantitatively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two animal models of intracellular TG accumulation, intrahepatic and intramyocellular TG accumulation was confirmed histologically. Consistent with the histological changes, the methylene signal intensity at 1.4 ppm increased in both liver and muscle, whereas the signal at 1.6 ppm was unchanged. In response to induced fat accumulation, the TG concentration in liver derived from 1H MRS increased from 0 to 44.9 ± 13.2 μmol/g, and this was matched by increases measured biochemically (2.1 ± 1.1 to 46.1 ± 10.9 μmol/g). Supportive evidence that the methylene signal at 1.6 ppm in muscle is derived from investing interfacial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease characterized by absence of interfacial fat, no signal was detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An identical methylene chemical shift at 1.4 ppm was obtained in human subjects with fatty liver where the fat is located exclusively within hepatocytes. In experimental animals, there was a close correlation between hepatic TG content measured in vivo by 1H MRS and chemically by liver biopsy [R = 0.934; P < .0001; slope 0.98, confidence interval (CI) 0.70-1.17; y-intercept 0.26, CI -0.28 to 0.70]. When applied to human calf muscle, the coefficient of variation of the technique in measuring intramyocellular TG content was 11.8{\%} in nonobese subjects and 7.9{\%} in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5{\%}, respectively. This study demonstrates for the first time that noninvasive in vivo 1H MRS measurement of intracellular TG, including that within myocytes, is feasible at 1.5-T field strengths and is comparable in accuracy to biochemical measurement. In addition, in mixed tissue such as muscle, the method is clearly advantageous in differentiating between TG from contaminating adipose tissue compared with intramyocellular lipids.",
keywords = "Congenital generalized lipodystrophy, Dog, Fatty acid analysis, Human, Liver, Proton, Quantification, Rabbit, Skeletal muscle",
author = "Szczepaniak, {Lidia S.} and Babcock, {Evelyn E.} and Fritz Schick and Dobbins, {Robert L.} and Abhimanyu Garg and Burns, {Dennis K.} and McGarry, {J. Denis} and Stein, {Daniel T.}",
year = "1999",
month = "5",
language = "English (US)",
volume = "276",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 39-5",

}

TY - JOUR

T1 - Measurement of intracellular triglyceride stores by 1H spectroscopy

T2 - Validation in vivo

AU - Szczepaniak, Lidia S.

AU - Babcock, Evelyn E.

AU - Schick, Fritz

AU - Dobbins, Robert L.

AU - Garg, Abhimanyu

AU - Burns, Dennis K.

AU - McGarry, J. Denis

AU - Stein, Daniel T.

PY - 1999/5

Y1 - 1999/5

N2 - We validate the use of 1H magnetic resonance spectroscopy (MRS) to quantitatively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two animal models of intracellular TG accumulation, intrahepatic and intramyocellular TG accumulation was confirmed histologically. Consistent with the histological changes, the methylene signal intensity at 1.4 ppm increased in both liver and muscle, whereas the signal at 1.6 ppm was unchanged. In response to induced fat accumulation, the TG concentration in liver derived from 1H MRS increased from 0 to 44.9 ± 13.2 μmol/g, and this was matched by increases measured biochemically (2.1 ± 1.1 to 46.1 ± 10.9 μmol/g). Supportive evidence that the methylene signal at 1.6 ppm in muscle is derived from investing interfacial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease characterized by absence of interfacial fat, no signal was detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An identical methylene chemical shift at 1.4 ppm was obtained in human subjects with fatty liver where the fat is located exclusively within hepatocytes. In experimental animals, there was a close correlation between hepatic TG content measured in vivo by 1H MRS and chemically by liver biopsy [R = 0.934; P < .0001; slope 0.98, confidence interval (CI) 0.70-1.17; y-intercept 0.26, CI -0.28 to 0.70]. When applied to human calf muscle, the coefficient of variation of the technique in measuring intramyocellular TG content was 11.8% in nonobese subjects and 7.9% in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5%, respectively. This study demonstrates for the first time that noninvasive in vivo 1H MRS measurement of intracellular TG, including that within myocytes, is feasible at 1.5-T field strengths and is comparable in accuracy to biochemical measurement. In addition, in mixed tissue such as muscle, the method is clearly advantageous in differentiating between TG from contaminating adipose tissue compared with intramyocellular lipids.

AB - We validate the use of 1H magnetic resonance spectroscopy (MRS) to quantitatively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two animal models of intracellular TG accumulation, intrahepatic and intramyocellular TG accumulation was confirmed histologically. Consistent with the histological changes, the methylene signal intensity at 1.4 ppm increased in both liver and muscle, whereas the signal at 1.6 ppm was unchanged. In response to induced fat accumulation, the TG concentration in liver derived from 1H MRS increased from 0 to 44.9 ± 13.2 μmol/g, and this was matched by increases measured biochemically (2.1 ± 1.1 to 46.1 ± 10.9 μmol/g). Supportive evidence that the methylene signal at 1.6 ppm in muscle is derived from investing interfacial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease characterized by absence of interfacial fat, no signal was detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An identical methylene chemical shift at 1.4 ppm was obtained in human subjects with fatty liver where the fat is located exclusively within hepatocytes. In experimental animals, there was a close correlation between hepatic TG content measured in vivo by 1H MRS and chemically by liver biopsy [R = 0.934; P < .0001; slope 0.98, confidence interval (CI) 0.70-1.17; y-intercept 0.26, CI -0.28 to 0.70]. When applied to human calf muscle, the coefficient of variation of the technique in measuring intramyocellular TG content was 11.8% in nonobese subjects and 7.9% in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5%, respectively. This study demonstrates for the first time that noninvasive in vivo 1H MRS measurement of intracellular TG, including that within myocytes, is feasible at 1.5-T field strengths and is comparable in accuracy to biochemical measurement. In addition, in mixed tissue such as muscle, the method is clearly advantageous in differentiating between TG from contaminating adipose tissue compared with intramyocellular lipids.

KW - Congenital generalized lipodystrophy

KW - Dog

KW - Fatty acid analysis

KW - Human

KW - Liver

KW - Proton

KW - Quantification

KW - Rabbit

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=0033007207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033007207&partnerID=8YFLogxK

M3 - Article

C2 - 10329993

AN - SCOPUS:0033007207

VL - 276

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 39-5

ER -