Metabolic biomarkers for non-alcoholic fatty liver disease induced by high-fat diet: In vivo magnetic resonance spectroscopy of hyperpolarized [1-13C] pyruvate

• Published in: Biochemical and biophysical research communications Vol. 482; no. 1; pp. 112 - 119
• Main Authors: Moon, Chung-Man, Oh, Chang-Hyun, Ahn, Kyu-Youn, Yang, Jun-Seok, Kim, Jae-Young, Shin, Sang-Soo, Lim, Hyo-Soon, Heo, Sook-Hee, Seon, Hyun-Ju, Kim, Jin-Woong, Jeong, Gwang-Woo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017
• Subjects: 60 APPLIED LIFE SCIENCES; Alanine - metabolism; ALANINES; Animals; BIOLOGICAL MARKERS; Biomarkers - metabolism; CARBON 13; Carbon-13 Magnetic Resonance Spectroscopy - methods; DIET; Diet, High-Fat; Dietary Fats - metabolism; DISEASES; Dynamic nuclear polarization (DNP); High-fat diet; Hyperpolarized 13C; LACTATE DEHYDROGENASE; Lactic Acid - metabolism; LIVER; MAGNETIC RESONANCE; Male; METABOLISM; Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - metabolism; Pyruvic Acid - pharmacokinetics; RATS; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; SPECTROSCOPY; NAFLD; Hyperpolarized 13C; Dynamic nuclear polarization (DNP); High-fat diet; Non-alcoholic fatty liver disease (NAFLD); Hyperpolarized C
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.08.118

Hyperpolarized 13C magnetic resonance spectroscopy (MRS) to assess hepatic metabolism in non-alcoholic fatty liver disease (NAFLD) has not been reported. This study searched for cellular metabolism-based biomarkers for NAFLD induced by a high-fat diet (HFD) in rats. Also, correlations of the biomarkers with enzyme levels and histopathology were identified during a 6-week follow-up. Six rats were fed a control diet (CD) and seven rats were fed the HFD for 6 weeks. Hyperpolarized 13C dynamic MRS was performed on rat liver following an injection of hyperpolarized [1-13C] pyruvate. Compared with CD-fed rats, HFD-fed rats showed significant increases in the levels of serum alanine aminotransferase and low-density lipoprotein cholesterol at weeks 4 and 6 of follow-up. After the 6-week HFD, the ratios of [1-13C] alanine/pyruvate and [1-13C] lactate/pyruvate were significantly increased, as were the levels of alanine aminotransferase and lactate dehydrogenase, which are potentially associated with hepatosteatosis. The results implicate [1-13C] alanine and [1-13C] lactate as potentially useful noninvasive biomarkers of hepatosteatosis occurring in NAFLD. [Display omitted] •Hyperpolarized 13C-alanine and lactate are noninvasive biomarkers on hepatosteatosis.•During the course of HFD feeding, 13C-alanine and lactate were increased in HFD-rats.•Hyperpolarized 13C dynamic MRS will be helpful to monitor the progression of NAFLD.