description
OBJECTIVE—Nonalcoholic fatty liver disease (NAFLD) is
linked to obesity and diabetes, suggesting an important role of
adipose tissue in the pathogenesis of NAFLD. Here, we aimed to
investigate the interaction between adipose tissue and liver in
NAFLD and identify potential early plasma markers that predict
nonalcoholic steatohepatitis (NASH).
RESEARCH DESIGN AND METHODS—C57Bl/6 mice were
chronically fed a high-fat diet to induce NAFLD and compared
with mice fed a low-fat diet. Extensive histological and phenotypical
analyses coupled with a time course study of plasma
proteins using multiplex assay were performed.
RESULTS—Mice exhibited pronounced heterogeneity in liver
histological scoring, leading to classification into four subgroups:
low-fat low (LFL) responders displaying normal liver morphology,
low-fat high (LFH) responders showing benign hepatic
steatosis, high-fat low (HFL) responders displaying pre-NASH
with macrovesicular lipid droplets, and high fat high (HFH)
responders exhibiting overt NASH characterized by ballooning of
hepatocytes, presence of Mallory bodies, and activated inflammatory
cells. Compared with HFL responders, HFH mice gained
weight more rapidly and exhibited adipose tissue dysfunction
characterized by decreased final fat mass, enhanced macrophage
infiltration and inflammation, and adipose tissue remodeling.
Plasma haptoglobin, IL-1, TIMP-1, adiponectin, and leptin were
significantly changed in HFH mice. Multivariate analysis indicated
that in addition to leptin, plasma CRP, haptoglobin,
eotaxin, and MIP-1 early in the intervention were positively
associated with liver triglycerides. Intermediate prognostic
markers of liver triglycerides included IL-18, IL-1, MIP-1, and
MIP-2, whereas insulin, TIMP-1, granulocyte chemotactic protein
2, and myeloperoxidase emerged as late markers.
CONCLUSIONS—Our data support the existence of a tight
relationship between adipose tissue dysfunction and NASH
pathogenesis and point to several novel potential predictive
biomarkers for NASH.
Objectives
—Nonalcoholic fatty liver disease (NAFLD) is
linked to obesity and diabetes, suggesting an important role of
adipose tissue in the pathogenesis of NAFLD. Here, we aimed to
investigate the interaction between adipose tissue and liver in
NAFLD and identify potential early plasma markers that predict
nonalcoholic steatohepatitis (NASH).
