Noninvasive assessment of hepatic lipid composition:... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders

Johnson, Nathan A.1,2; Walton, David W.3; Sachinwalla, Toos3; Thompson, Campbell H.4; Smith, Kate1; Ruell, Patricia A.1,2; Stannard, Stephen R.5; George, Jacob6*

1_Discipline of Exercise and Sport Science, The University of Sydney, Sydney, Australia_

2_Institute of Obesity, Nutrition and Exercise, The University of Sydney, Sydney, Australia_

3_Department of Magnetic Resonance, Rayscan Imaging, Liverpool, Australia_

4_Department of Medicine, Flinders University, Bedford Park, Australia_

5_Institute of Food, Nutrition and Human Health, Massey University, New Zealand_

6_Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, The University of Sydney, Sydney, Australia_

*Address reprint requests to: Department of Medicine, Westmead Hospital, Westmead NSW 2145, Australia

Email:[email protected]

Received 3 October 2007; Accepted 2 January 2008

Published online in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: Massey University Research Fund; Grant Number: 06/5062; Grant sponsor: Southern Adelaide Health Service; Grant sponsor: University of Sydney Faculty Financial Support Fund; Grant Number: S0717 0000; Grant sponsor: Robert W. Storr bequest to the University of Sydney and a program grant from the National Health and Medical Research Council; Grant Number: 358398.

Potential conflict of interest: Nothing to report.

fax: 9635-7582.

Abstract

Nonalcoholic fatty liver is frequently observed in obese individuals, yet the factors that predict its development and progression to liver disease are poorly understood. We proposed that proton magnetic resonance spectroscopy (1H-MRS) might allow noninvasive assessment of hepatic lipid composition. Lipid saturation (SI) and polyunsaturation (PUI) indices measured by 1H-MRS were in agreement with those expected in oils of known composition. Hepatic triglyceride concentration (HTGC) and composition were then measured in healthy lean (LEAN) men, obese men with normal HTGC (OB), and obese men with hepatic steatosis (OB+HS). The effect of marked changes in dietary fat consumption on hepatic lipids were also compared in lean men after 67 hours of a normal mixed (NM) diet versus a low-carbohydrate, high-saturated-fat (LCHF) diet. SI was significantly higher in OB+HS (0.970 ± 0.004) and OB (0.944 ± 0.008) versus LEAN (0.818 ± 0.025) ( P < 0.01 for both). PUI was significantly lower in OB+HS (0.003 ± 0.001) and OB (0.022 ± 0.005) versus LEAN (0.120 ± 0.021) (P < 0.01), and significantly lower in OB+HS versus OB (** **_P_** **< 0.05). LCHF diet did not alter HTGC, SI, or PUI (** **_P_** **> 0.05). The 1H-MRS method provides for rapid, qualitative assessment of lipid composition. Application of this technique in the liver produces results that are consistent with biopsy-based approaches demonstrating that relative hepatic lipid saturation increases and polyunsaturation decreases with obesity. Obesity-related hepatic steatosis is characterized by further depletion of polyunsaturated hepatic lipids. Conclusion: This readily available and noninvasive approach should promote further study into interactions between hepatic and whole-body lipid metabolism and help to elucidate the pathogenesis of disorders characterized by lipid accumulation within the liver.

Abbreviations: BFU, burst-forming unit; CFU, colony forming unit; CH2-, methylene; CH3, methyl; Cre, cyclization recombination; ER, endoplasmic reticulum; FFA, free fatty acid; Foxa, forkhead box family member; 1H-MRS, proton magnetic resonance spectroscopy; HOMAIR, homeostasis model assessment of insulin resistance; HTGC, hepatic triglyceride concentration; LCHF, low-carbohydrate high-saturated fat diet; LEAN, lean men; LEF, lymphoid enhancement factor; loxP, Locus of X-over P1; LRP, LDL (low density lipoprotein)-related protein; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NM, normal mixed diet; OB, obese men with normal HTGC; OB+HS, obese men with hepatic steatosis; PUFA, polyunsaturated fatty acid; PUI, polyunsaturation index; QUEST, quantitation based on quantum estimation; SI, saturation index; TCF, T-cell factor; UI, unsaturation index; ZO-1, Zonula occludens-1.