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Lipid Emulsion Halts the Progression of Non‐Alcoholic Fatty Liver Disease (NAFLD) in Nonobese Mice Fed a Liquid High Carbohydrate Diet
Author(s) -
Huang KuanHsun,
Hao Lei,
Smith Philip,
Patterson Andrew,
Ross A Cathatine
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.743.14
Subject(s) - medicine , lipogenesis , endocrinology , fatty liver , lipotoxicity , chemistry , carbohydrate , fatty acid synthase , unsaturated fat , lipid metabolism , saturated fat , insulin resistance , cholesterol , disease , insulin
A two‐hit hypothesis has been proposed for the etiology of NAFLD: first, increased lipogenesis results in triacylglycerol (TG) accumulation, then inflammatory stimuli, e.g., saturated fatty acids (SFA)‐induced lipotoxicity and inflammation, cause disease progression. Previously, we showed that NAFLD‐like symptoms developed in mice fed a liquid high carbohydrate diet (76% en‐%, HCD) for 5‐wk, while mice fed HCD containing 13.5% (en‐%) of lipid emulsion (LE, Intralipid®) exhibited less hepatic TG accumulation and inflammation. However, it is unknown whether LE can cease the first hit of NAFLD once TG accumulation has begun. To test this, male C57BL/6 mice (6 wk; n =8/group) were fed either HCD for 5 wk (HCD) or HCD for 2.5 wk followed by HCD with LE for 2.5 wk (HCD/LE). At this time, liver TG in mice fed HCD/LE was 60% lower ( P <0.001) as compared to mice fed HCD. Hepatic mRNAs of PNPLA3, associated with NAFLD,and several lipogenic genes, e.g., acetyl‐CoA carboxylase 1, fatty acid synthase, and stearoyl‐CoA desaturase 1, assayed by qRT‐PCR, were decreased by 42‐93% in HCD/LE vs. HCD mice (all P <0.001). We further analyzed liver total fatty acid composition, determined as fatty acid methyl esters by GC‐MS, and found that HCD/LE mice had lower levels of C14:0, C16:0 and C18:1 ( n ‐9) as compared to HCD mice (all P <0.001). In conclusion, in the presence of a HCD, LE can halt the first hit of NAFLD and lower the levels of saturated FA, reducing lipotoxicity and lipogenesis.